Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylated osteopontin peptides suppress crystallization by inhibiting the growth of calcium oxalate crystals.

BACKGROUND Osteopontin isolated from human urine [uropontin (uOPN)] is a potent inhibitor of calcium oxalate (CaOx) monohydrate (COM) crystallization. However, specific structural features responsible for its effects on CaOx crystallization were not previously known. The present studies were designed to define molecular features responsible for interactions of uOPN with COM crystals and the inhibition of crystallization. METHODS Peptides and phosphopeptides with sequences corresponding to potential crystal binding domains within the protein sequence of osteopontin were synthesized. Then the effects of these peptides on COM crystal growth and crystal aggregation were investigated and their secondary structures analyzed. RESULTS Growth of COM crystals was inhibited by approximately 50% at 1000 nmol/L concentrations by the two unmodified peptides with the closest clustering of aspartic acid residues. Growth was not inhibited by the other two unmodified peptides, with aspartic residues more evenly distributed within their sequences. Phosphorylation markedly increased inhibition of COM crystal growth, so that each of the four phosphorylated peptides inhibited growth by at least 50% at concentrations of < or =200 nmol/L. Phosphorylation of these peptides did not cause changes in secondary structure that would favor interaction with COM crystal surfaces. CONCLUSIONS These studies of synthetic peptides identify molecular features within the osteopontin molecule that contribute to the inhibition of one aspect of COM crystallization. The inhibition of crystal growth induced by phosphorylation appears to result from altered local patterns of charge density, since conformational changes favoring interaction with crystals were not caused by phosphorylation.
Intersecting identities and substance use problems: sexual orientation, gender, race, and lifetime substance use problems.

OBJECTIVE Research has documented that sexual minorities are at greater risk for substance use than heterosexuals. However, there are limited studies and mixed findings when investigating these health disparities among racial and ethnic minority samples. We used an intersectionality framework to examine disparities in lifetime substance use problems between heterosexual and sexual minority men and women and within sexual minority groups among a racially diverse sample. METHOD A nonprobability sample of heterosexual (n = 1,091) and sexual minority (n = 1,465) patients from an urban community health center ranged in age from 18 to 72 years. Participants completed a brief patient survey and reported demographic information and history of lifetime substance use problems. Logistic regressions analyses were used to examine interactions between and among sexual orientation, gender, and race. RESULTS We found a significant three-way interaction among sexual orientation, gender, and race. Sexual minorities had a greater risk of self-reported lifetime substance use problems than heterosexuals, with nuanced gender and racial differences. Of greatest note, sexual minority women of color had greater risks than heterosexual women of color and than White sexual minority women. Sexual minority men of color did not differ in their risk when compared with heterosexual men of color, and they had lower risk than White sexual minority men. CONCLUSIONS The results of this study demonstrate that an intersectionality framework is crucial to clearly identify lifetime substance use disparities between racially diverse sexual minority and heterosexual men and women. Future research, treatment, and policy should use intersectionality approaches when addressing substance use disparities.
Vitamin D3 accelerates PTH-dependent calcium transport in distal convoluted tubule cells.

This study examined the interaction of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] and parathyroid hormone (PTH) on Ca2+ uptake, intracellular Ca2+ ([Ca2+]i) and membrane voltage in transformed mouse distal convoluted tubule (DCT) cells. 1,25(OH)2D3 increased PTH-dependent 45Ca2+ uptake by 2 h and was maximally stimulated at 5 h over the range of 10(-11) to 10(-9) M 1,25(OH)2D3. [Ca2+]i was measured in single cells grown on cover slips and loaded with fura-2. In control cells [Ca2+]i averaged 109 nM and was not changed by acute addition of 1,25(OH)2D3 (10(-7) M) alone or by pretreatment with 1,25(OH)2D3 for 5 h. The magnitude of the bPTH-(1-34)-stimulated increase of [Ca2+]i was similar in control cells and in cells pretreated with 1,25(OH)2D3. In cells pretreated with 1,25(OH)2D3 the latency before [Ca2+]i increased, following addition of PTH, was reduced from 8.6 min to 3.5 +/- 0.9 min (P < 0.01). 1,25(OH)2D3 alone had no effect on 45Ca2+ uptake but shortened the time course of PTH-dependent 45Ca2+ uptake. The inactive vitamin D analogue, 25-hydroxyvitamin D3 (10(-7) M) (with or without PTH), did not affect 45Ca2+ uptake. Inhibition of transcription with 5-6-dichloro-1-beta-D- ribofuranosylbenzimidazole abolished the effect of 1,25(OH)2D3, but not that of PTH. Treatment with 1,25(OH)2D3 also decreased the latency but not the magnitude of membrane hyperpolarization induced by PTH. Nifedipine abolished PTH-induced increases of [Ca2+]i and 45Ca2+ entry in cells pretreated with 1,25(OH)2D3. (ABSTRACT TRUNCATED AT 250 WORDS)
Interneurones in pathways from group II muscle afferents in the lower‐lumbar segments of the feline spinal cord

Interneurones receiving excitatory input from group II muscle afferents of hindlimb nerves and located in the lower‐lumbar (L6‐L7) segments of the cat spinal cord were investigated using both extracellular and intracellular recording. The interneurones were located mainly in the lateral parts of laminae IV‐VII, dorsal and lateral to the main region in which interneurones with input from group I muscle afferents are located. Almost half the sample of interneurones (38 of 76) were characterized by an ipsilateral ascending projection within the lateral funiculus to the L4 level. The most powerful group II excitation was produced by afferents of the quadriceps and deep peroneal muscle nerves (which discharged 70–80 % of extracellularly recorded neurones) while group II afferents of tibialis posterior, posterior biceps‐semitendinosus and gastrocnemius soleus were also highly effective (discharging 45–55 % of extracellularly recorded neurones). A proportion of intracellularly recorded group II EPSPs were monosynaptic. Seventy‐five per cent of the extracellularly recorded interneurones were discharged by group II afferents of two or more muscle nerves and 43 % by afferents of three or more nerves. Group I muscle afferents evoked small EPSPs in over one‐quarter of the intracellularly recorded interneurones and virtually all were strongly excited by cutaneous afferents. Evidence of excitatory input from joint, interosseous and group III muscle afferents was also observed. The properties of the interneurones are compared with those of others in the lumbosacral segments and the possibility that they may function as last‐order premotor interneurones is discussed.
Multiple T cell specificities for Bet v I, the major birch pollen allergen, within single individuals. Studies using specific T cell clones and overlapping peptides

Twenty‐five T cell clones specific for Bet v I were established from the peripheral blood of two birch pollen‐allergic patients. The T cell epitopes of these clones were mapped using dodecapeptides overlapping for 2 amino acids (neighbors share 10 residues) spanning the whole amino acid sequence of the protein (159 amino acids). In total, 7 epitopes could be detected. One donor displayed 6 distinct T cell specificities for the Bet v I molecule in 14 T cell clones; for the other donor, 4 stimulating peptides for 11 clones could be identified. Two T cell epitopes were recognized by both subjects. One of these might represent an immunodominant epitope located at amino acid position 77–92 of the Bet v I molecule, as in 13/25 T cell clones activation could be induced by this amino acid sequence. One T cell clone reacted with purified pollen‐derived Bet v I, but neither with any peptide synthesized according to a Bet v I‐encoding cDNA nor with the respective recombinant protein.
Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population

The main focus of this German‐wide multi‐center study was to establish a BRCA1/2 mutation profile and to determine family types with high frequencies of mutations in these genes. In a comprehensive study, the entire coding sequences of the breast cancer genes BRCA1 and BRCA2 were analyzed in 989 unrelated patients from German breast/ovarian cancer families. A total of 77 BRCA1 and 63 BRCA2 distinct deleterious mutations were found in 302 patients. More than ⅓ of these mutations are novel and might be specific for the German population. Eighteen common mutations were found in 68% of cases in BRCA1 and 13 recurrent mutations in 44% of cases in BRCA2, facilitating prescreening approaches. Haplotype analysis indicate that 14 out of 20 recurrent mutations are likely originating from a common founder. An additional 50 different rare sequence variants with unknown relevance for tumorigenesis were found in 72 families. Correlation of BRCA1/BRCA2 detection rates with family history identified families with both breast and ovarian cancer to be at highest risk for BRCA1/BRCA2 mutations (43% and 10%, respectively), followed by families with at least 2 premenopausal cases of breast cancer (24% BRCA1 and 13% BRCA2 mutations). These data provide strong evidence for further predisposing genes in the German population. In breast cancer families with 2 or 3 affected females but only a single or no premenopausal case, mutations were detected with low frequencies (about 10% or less for both genes). The decision for or against molecular diagnosis is now aided by considering the expected mutation detection rates that greatly depend on family history and structure. © 2001 Wiley‐Liss, Inc.
Impact of high-dose corticosteroid therapy for patients with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome.

OBJECTIVE The purpose of this study was to determine whether corticosteroid administration to patients with antepartum HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome would alter laboratory values diagnostic for the disease. STUDY DESIGN Cases of 37 women with antepartum HELLP syndrome managed between March 1995 and July 1999 were reviewed. Patients were classified on the basis of exposure to corticosteroids and to the dose used. Group 1 did not receive corticosteroids. Group 2 received a standard corticosteroid dosage regimen for promotion of fetal lung maturation. Group 3 received a high-dose corticosteroid regimen of >24 mg/d (most frequently 10 mg dexamethasone as an intravenous bolus dose every 6 hours for 2 doses followed by 6 mg as an intravenous bolus dose every 6 hours for 2 to 4 doses). Antepartum changes in laboratory values from diagnosis to delivery were evaluated by means of the Kruskal-Wallis test. RESULTS Eleven patients did not receive corticosteroids, 15 were given a standard dose, and 11 received high-dose therapy. For each laboratory value assessed (platelet count, aspartate aminotransferase activity, and lactate dehydrogenase activity), the corticosteroid groups differed significantly from the no-treatment group (P </=.002 for all). A further, significantly greater improvement in platelet count was noted between the high-dose group (81%) and the standard-dose group (17%; P =.04). The interval from diagnosis to delivery was also longer for patients treated with the high-dose protocol (51 +/- 25 hours) than for both those treated with a standard regimen (26 +/- 20 hours) and those who received no treatment (13 +/- 11 hours; P <. 001). CONCLUSION Administration of corticosteroids to patients with antepartum HELLP syndrome improves platelet count, reduces liver enzyme abnormalities, and prolongs latency to delivery in a dose-dependent manner. Higher doses of corticosteroid than those traditionally prescribed for promotion of fetal pulmonary maturation should be considered for maternal and fetal benefits in cases of severe preeclampsia.
Frequency and patterns of mental health services utilization among adolescents with anxiety and depressive disorders

The main aim of this study was to examine the frequency and patterns of mental health services utilization among 12‐ to 17‐year‐old adolescents with anxiety and depressive disorders. Another aim was to examine the factors associated with the use of mental health services. The study population comprised 1,035 adolescents randomly recruited from 36 schools. Anxiety and depressive disorders were coded based on DSM‐IV criteria using the computerized Munich version of the Composite International Diagnostic Interview. Only 18.2% of the adolescents who met DSM‐IV criteria for anxiety disorders, and 23% of those with depressive disorders, used mental health services. Among adolescents with anxiety disorders, mental health services utilization was associated with past suicide attempt, older age, the presence of comorbid disorders, as well as parental anxiety and depression. The only factor that predicts the use of mental health service among adolescents with depressive disorder was a history of suicide attempt. The implication of the results in terms of tailoring services for children and adolescents with anxiety and depressive disorders are discussed. Depression and Anxiety 22:130–137, 2005. © 2005 Wiley‐Liss, Inc.
Central projections of auditory‐nerve fibers of differing spontaneous rate. I. Anteroventral cochlear nucleus

Auditory nerve fibers have been subdivided into three functional groups (Liberman, M.C. [1978] J. Acoust. Soc. Am. 63:442–455) differing in acoustic sensitivity and spontaneous discharge rate (SR). Using intracellular injection of horseradish peroxidase, the present study analyzes the projections of these three neuronal subclasses to the various subdivisions of the anteroventral cochlear nucleus (AVON) and to the different cell types found therein. The average number of swellings and number of cells contacted decreased from low‐ to medium‐ to high‐SR groups. However, these differences in terminal elaboration were not evenly distributed throughout the AVCN. The small cell cap was almost exclusively innervated by low‐ and medium‐SR fibers, i.e., those with the highest acoustic thresholds. Within anterior AVCN, spherical‐cell innervation was seen from all SR groups, whereas almost all multipolar cell innervation was from low‐ and medium‐SR fibers. In the posterior AVCN, multipolar‐cell innervation was equally likely from all SR groups, whereas globular cells were preferentially contacted by high‐SR fibers. These SR‐based trends in cochlear nucleus innervation help explain some of the known physiological properties of cell‐types in each subdivision. They also suggest that additional physiological study of the small cell cap may be key in elucidating the functional significance of the low‐SR population.
Hyperhomocysteinemia and MTHFR polymorphisms in association with orofacial clefts and congenital heart defects: A meta‐analysis

Several studies have reported an association between hyperhomocysteinemia, 5,10‐methylenetetrahydrofolate reductase (MTHFR) polymorphisms and cleft lip with or without cleft palate (CLP), and congenital heart defects (CHDs). However, findings have been inconsistent. A meta‐analysis was performed of published studies until September 2006 investigating these associations in both mothers and children. Homocysteine data were provided in two CLP and three CHD studies, and MTHFR polymorphisms were reported in ten CLP and eight CHD studies. Data were analyzed using the random effects model in the Cochrane Review Manager. The pooled odds ratio (OR) of maternal hyperhomocysteinemia was 2.3 (95% CI 0.4–11.9) for CLP, and 4.4 (2.6–7.3) for CHDs. The MTHFR C677T polymorphism and CLP showed pooled ORs of 1.2 (0.9–1.5) in mothers and 1.0 (0.9–1.2) in children, whereas these estimates for the A1298C polymorphism were 1.0 (0.7–1.2) in mothers and 0.9 (0.6–1.2) in children. The MTHFR C677T polymorphism in CHD studies demonstrated a pooled OR of 1.0 (0.8–1.3) for mothers and 1.1 (0.9–1.5) for children. Two studies investigating the maternal A1298C polymorphism in CHDs demonstrated a pooled OR of 1.2 (0.8–1.8). Only one CHD study reported an OR of 1.3 (0.8–2.1) for this polymorphism in children. In conclusion, this meta‐analysis demonstrates that maternal hyperhomocysteinemia is a risk factor for CHDs. The MTHFR polymorphisms C677T and A1298C in both mothers and children are not independently associated with CLP or CHDs. Future studies should be performed to investigate the interactions between maternal hyperhomocysteinemia, B‐vitamin intake, related polymorphisms and the risk of CLP and CHDs. © 2007 Wiley‐Liss, Inc.
Modular Structure of PACT: Distinct Domains for Binding and Activating PKR

ABSTRACT PACT is a 35-kDa human protein that can directly bind and activate the latent protein kinase, PKR. Here we report that PKR activation by PACT causes cellular apoptosis in addition to PKR autophosphorylation and translation inhibition. We analyzed the structure-function relationship of PACT by measuring its ability to bind and activate PKR in vitro and in vivo. Our studies revealed that among three domains of PACT, the presence of either domain 1 or domain 2 was sufficient for high-affinity binding of PACT to PKR. On the other hand, domain 3, consisting of 66 residues, was absolutely required for PKR activation in vitro and in vivo. When fused to maltose-binding protein, domain 3 was also sufficient for efficiently activating PKR in vitro. However, it bound poorly to PKR at the physiological salt concentration and consequently could not activate it properly in vivo. As anticipated, activation of PKR by domain 3 in vivo could be restored by attaching it to a heterologous PKR-binding domain. These results demonstrated that the structure of PACT is modular: it is composed of a distinct PKR-activation domain and two mutually redundant PKR-interacting domains.
In fl uence of Rifampicin on the Pharmacokinetics of Salvianolic Acid B May Involve Inhibition of Organic Anion Transporting Polypeptide ( Oatp ) Mediated In fl ux

This article studied the possible effect of rifampicin (RIF), an inhibitor of organic anion transporting polypeptide (Oatp), on the pharmacokinetics of salvianolic acid B (SAB) in rats. Rifampicin was administered intravenously 15min prior to SAB (5mg/kg) in rats at doses of 0, 5.0, 10.0 and 20.0mg/kg, respectively. The concentrations of SAB in plasma and bile were determined using a Shimadzu HPLC system coupled to a LC‐MS‐2010EV mass spectrometer. Compared with the control group, the AUC0‐t and Cmax values of SAB were increased significantly, while the CLtotal and CLbile were decreased significantly. These results suggested that pretreatment with rifampicin prior to SAB administration could decrease significantly the total and bile elimination of SAB and alter its pharmacokinetic profi les. The influence of rifampicin on the pharmacokinetics of SAB may be attributed to the inhibition of Oatp‐mediated influx. Copyright © 2011 John Wiley & Sons, Ltd.
Impact of drug-eluting stents on outcomes of patients with end-stage renal disease undergoing percutaneous coronary revascularization.

BACKGROUND AND OBJECTIVE End-stage renal disease (ESRD) patients on chronic dialysis are at heightened risk for target vessel revascularization (TVR) after coronary stenting. However, ESRD patients were excluded from the trials that demonstrated the superiority of drug-eluting stents (DES) over bare metal stents (BMS) in reducing TVR. We sought to identify the impact of stent type (DES versus BMS) on TVR and other cardiac adverse events in ESRD patients. METHODS The study included 89 consecutive ESRD patients who underwent coronary stenting and were followed for greater than or equal to 9 months. TVR was the primary endpoint, and the secondary endpoint was a composite of death, myocardial infarction (MI) and TVR. Multivariate logistic regression models were used to adjust for differences in clinical and procedural characteristics. RESULTS DES were used in 24 and BMS in 65 patients. The stent diameter was smaller (p = 0.008), but the stent length was longer (p = 0.006) in the DES group. TVR was required in 1 (4%) of DES and 17 (26%) BMS patients, while 8 (33%) DES and 39 (60%) BMS patients met the secondary endpoint. By multivariate logistic regression, DES use was associated with a significant reduction in TVR (OR 0.07, 95% CI 0.006-0.844; p = 0.036) and a significant reduction in death, MI and TVR (OR 0.11, 95% CI 0.022-0.513; p = 0.005). CONCLUSION A high rate of ischemic events was noted for ESRD patients, regardless of stent type. However, in ESRD patients undergoing coronary revascularization, DES use is effective in reducing 9-month TVR and the composite of death, MI and TVR.
School and Community Screening Shows Malawi, Africa, to Have a High Prevalence of Latent Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is the largest cardiac cause of morbidity and mortality in the world's youth. Early detection of RHD through echocardiographic screening in asymptomatic children may identify an early stage of disease, when secondary prophylaxis has the greatest chance of stopping disease progression. Latent RHD signifies echocardiographic evidence of RHD with no known history of acute rheumatic fever and no clinical symptoms. OBJECTIVE Determine the prevalence of latent RHD among children ages 5-16 in Lilongwe, Malawi. DESIGN This is a cross-sectional study in which children ages 5 through 16 were screened for RHD using echocardiography. SETTING Screening was conducted in 3 schools and surrounding communities in the Lilongwe district of Malawi between February and April 2014. OUTCOME MEASURES Children were diagnosed as having no, borderline, or definite RHD as defined by World Heart Federation criteria. The primary reader completed offline reads of all studies. A second reader reviewed all of the studies diagnosed as RHD, plus a selection of normal studies. A third reader served as tiebreaker for discordant diagnoses. The distribution of results was compared between gender, location, and age categories using Fisher's exact test. RESULTS The prevalence of latent RHD was 3.4% (95% CI = 2.45, 4.31), with 0.7% definite RHD and 2.7% borderline RHD. There was no significant differences in prevalence between gender (P = .44), site (P = .6), urban vs. peri-urban (P = .75), or age (P = .79). Of those with definite RHD, all were diagnosed because of pathologic mitral regurgitation (MR) and 2 morphologic features of the mitral valve. Of those with borderline RHD, most met the criteria by having pathological MR (92.3%). CONCLUSION Malawi has a high rate of latent RHD, which is consistent with other results from sub-Saharan Africa. This study strongly supports the need for a RHD prevention and control program in Malawi.
IMP Dehydrogenase-Linked Retinitis Pigmentosa

Many retinal diseases are caused by mutations in photoreceptor-specific proteins. However, retinal disease can also result from mutations in widely expressed proteins. One such protein is inosine monophosphate dehydrogenase type 1 (IMPDH1), which catalyzes a key step in guanine nucleotide biosynthesis and also binds single-stranded nucleic acids. The pathogenic IMPDH1 mutations are in or near the CBS domains and do not affect enzymatic activity. However, these mutations do decrease the affinity and specificity of single-stranded nucleic acid binding. These observations suggest that IMPDH1 has a previously unappreciated role in RNA metabolism that is crucial for photoreceptor function.