Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidermal growth factor promotes proliferation and maintains multipotency of continuous cultured adipose stem cells via activating STAT signal pathway in vitro

Abstract This study aimed to investigate the effects of epidermal growth factor (EGF) on the proliferation and differentiation of adipose stem cells (ASC) during the repeated passaging and probe the underlying signal pathway. Results showed that the Ki67 positive rate remained at a high level, the number of ASCs in G0/G1 phase reduced significantly, but ASCs in G2/M phase and S phase increased markedly in ASCs treated with EGF when compared with ASCs without EGF treatment, indicating that EGF made more ASCs in proliferation phase. The adipogenic capability of ASCs without EGF was compromised when compared with that of ASCs after EGF treatment, although significant difference was not observed. The osteogenic and chondrogenic potencies increased significantly in ASC with EGF treatment indicating EGF could maintain differentiative capacity of ASCs. Gene Set Enrichment Analysis showed EGF upregulated the expression of molecules in the epithelial mesenchymal transition and G2/M checkpoint signal pathways. GeneMANIA database analysis indicated the network interaction between EGF and STAT. EGF receptor (EGFR) inhibitor and STAT3 inhibitor were independently used to validate the role of both pathways in these effects. After inhibition of EGFR or STAT3, the proliferation of ASCs was significantly inhibited, and Western blotting showed EGF was able to markedly increase the expression of EGFR and STAT3. These findings suggest EGF not only promotes the proliferation of ASCs and delays their senescence, but also maintains the differentiation potency of ASCs, which are related to the EGF-induced activation of STAT signal pathway.
InvF Is Required for Expression of Genes Encoding Proteins Secreted by the SPI1 Type III Secretion Apparatus inSalmonella typhimurium

ABSTRACT The expression of genes encoding proteins secreted by the SPI1 (Salmonella pathogenicity island) type III secretion apparatus is known to require the transcriptional activators SirA and HilA. However, neither SirA nor HilA is believed to directly activate the promoters of these genes. invF, the first gene of theinv-spa gene cluster, is predicted to encode an AraC-type transcriptional activator and is required for invasion into cultured epithelial cells. However, the genes which are regulated by InvF have not been identified. In this work, an in-frame deletion ininvF was constructed and tested for the expression of Φ(sigD-lacZYA),sipC::Tn5lacZY, and a plasmid-encoded Φ(sicA-lacZYA). SigD (Salmonella invasion gene) is a secreted protein required for the efficient invasion ofSalmonella typhimurium into cultured eucaryotic cells.sicA (Salmonella invasion chaperone) is the first gene of a putative operon encoding the Sip/Ssp (Salmonella invasion/Salmonella secreted proteins) invasion proteins secreted by the SPI1 type III export apparatus. invF was required for the expression of thesigD, sicA, and sipC fusions. This is the first demonstration that there is a functional promoter in the intergenic sequence between spaS and sicA. In addition, several proteins were either absent from or found in reduced amounts in the culture supernatants of the invF mutant. Therefore, invF is required for the optimal expression of several genes encoding SPI1-secreted proteins. Genetic evidence is also presented suggesting there is HilA-dependent readthrough transcription from the invF promoter at least through sipC.
Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease.

BACKGROUND AND OBJECTIVES Monoclonal free light chains (FLC) frequently cause kidney disease in patients with plasma cell dyscrasias. Polyclonal FLC, however, have not been assessed in patients with chronic kidney disease (CKD) yet could potentially play an important pathologic role. This study describes for the first time polyclonal FLC in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A sensitive, quantitative immunoassay was used to analyze serum and urinary polyclonal FLC in 688 patients with CKD of various causes. RESULTS Serum kappa and lambda FLC concentrations increased progressively with CKD stage (both P < 0.001) and strongly correlated with markers of renal function, including cystatin-C (kappa: R = 0.8, P < 0.01; and lambda: R = 0.79, P < 0.01). Urinary FLC concentrations varied significantly between disease groups (kappa: P < 0.001; lambda: P < 0.005) and also rose significantly with increasing CKD stage (both FLC P < 0.0001). Urinary FLC concentrations were positively correlated with their corresponding serum concentration (kappa: R = 0.63; lambda: R = 0.65; both P < 0.001) and urinary albumin creatinine ratio (kappa: R = 0.58; lambda: R = 0.65; both P < 0.001). The proportion of patients with abnormally high urinary FLC concentrations rose with both the CKD stage and the severity of albuminuria. CONCLUSIONS This study demonstrates significant abnormalities of serum and urinary polyclonal FLC in patients with CKD. These data provide the basis for studies that assess the contribution of polyclonal FLC to progressive renal injury and systemic inflammation in patients with kidney disease.
Effects of right ventricular pacing sites on blood pressure variation in upright posture: a comparison of septal vs. apical pacing sites.

AIMS Large variations in blood pressure (BP) in the upright position are a major cause of pacemaker syndrome, observed in up to 80% of patients paced non-physiologically at the right ventricular (RV) apex. We hypothesized that the magnitude of BP variations might be influenced by the RV pacing site. To assess this, we compared haemodynamic findings during supine and upright posture with RV apical vs. septal pacing. METHODS AND RESULTS The study population comprised a retrospective cohort of 24 dual-chamber pacemaker patients with advanced or complete atrioventricular block, in which 11 were randomly chosen from those with RV apical pacing, and 13 randomly chosen from those with septal pacing. Studies were performed during fixed rate VVI and DDD pacing modes with patients in both supine and passive head-up tilt positions. Continuous BP, stroke volume, cardiac index, and total peripheral resistance index were measured non-invasively. During RV apical pacing, there were significant differences of beat-to-beat BP variation after movement from supine to upright posture for both VVI and DDD pacing modes (P < 0.05); however, this was not the case for either mode during RV septal pacing. Further, comparing RV apical to RV septal pacing in the supine position, there were no BP variation differences for either DDD or VVI modes. Conversely, in the upright position BP variation was significantly greater during RV apical vs. RV septal VVI pacing (P = 0.017) but not during DDD pacing. CONCLUSION During VVI pacing, RV septal pacing exhibited lesser BP variation during upright posture compared with RV apical pacing.
Increased frequency of p53 mutation in sporadic colorectal cancer from cigarette smokers.

BACKGROUND Cigarette smoking has been shown to increase the risk of colorectal cancer. However, the relation between smoking and genetic alterations has not been clarified in this type of cancer. METHODS Mutations of p53, APC, beta-catenin and K-ras-2 genes were analyzed in colorectal carcinomas from 28 smokers and 33 non-smokers. Frequencies and types of mutations were compared between smokers and non-smokers. RESULTS The frequency of carcinomas with p53 mutation was higher in smokers (20/28, 71%) than in non-smokers (15/33, 45%) (P = 0.037). The common type of mutation was single-base substitution including G:C to A:T transition in both groups (68% in smokers and 67% in non-smokers). With respect to G:C to A:T transitions, mutation at CpG sites was less frequent in smokers (9/15, 60%) than in non-smokers (10/10, 100%), whereas mutation at non-CpG sites was more frequent in smokers (6/16, 40%) than in non-smokers (0/10, 0%) (P = 0.028). The frequency of APC mutation was not significantly different between smokers (14/28, 50%) and non-smokers (15/33, 45%). No beta-catenin mutation was detected in carcinomas from smokers. K-ras-2 mutation occurred in smokers at a similar frequency (9/28, 32%) to that in non-smokers (13/33, 39%). Concerning pathological aspects, Dukes' A carcinomas were less frequent in smokers (11%) than in non-smokers (33%), whereas Dukes' D carcinomas were more frequent in smokers (25%) than in non-smokers (15%). CONCLUSION The present results suggest that an increased frequency of p53 gene mutation, including G:C to A:T transitions at non-CpG sites, is associated with an increased risk of colorectal carcinogenesis in cigarette smokers.
"Tennis Elbow": A Manual Therapist's Perspective.

Ever since the turn of this century the pathogenetic mechanism of "tennis elbow" has been a controversial issue. The following article briefly describes the varying opinions and then proposes a working hypothesis to explain the unpredictable presentation of lateral forearm pain. The articular mechanics of the elbow joint are described in detail followed by a discussion of intrinsic and extrinsic factors pertinent to tennis elbow. The intent is to logically present a multifactorial syndrome, such as tennis elbow, from the perspective of manual therapy which incorporates a global evaluation of the clinical picture. J Orthop Sports Phys Ther 1986;8(3):134-142.
Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia

We hypothesize that circadian dysfunction could underlie, at least partially, the liability for bipolar 1 disorder (BD1). Our hypothesis motivated tests for the association between the polymorphisms of genes that mediate circadian function and liability for BD1. The US Caucasian patients with BD1 (DSM‐IV criteria) and available parents were recruited from Pittsburgh and surrounding areas (n = 138 cases, 196 parents) and also selected from the NIMH Genetics Collaborative Initiative (n = 96 cases, 192 parents). We assayed 44 informative single‐nucleotide polymorphisms (SNPs) from eight circadian genes in the BD1 samples. A population‐based sample, specifically cord blood samples from local live births, served as community‐based controls (n = 180). It was used as a contrast for genotype and haplotype distributions with those of patients. US patients with schizophrenia/schizoaffective disorder (SZ/SZA, n = 331) and available parents from Pittsburgh (n = 344) were assayed for a smaller set of SNPs based on the results from the BD1 samples. Modest associations with SNPs at ARNTL (BmaL1) and TIMELESS genes were observed in the BD1 samples. The associations were detected using family‐based and case–control analyses, albeit with different SNPs. Associations with TIMELESS and PERIOD3 were also detected in the Pittsburgh SZ/SZA group. Thus far, evidence for association between specific SNPs at the circadian gene loci and BD1 is tentative. Additional studies using larger samples are required to evaluate the associations reported here.
Distribution of Cryptosporidium Genotypes in Storm Event Water Samples from Three Watersheds in New York

ABSTRACT To assess the source and public health significance of Cryptosporidium oocyst contamination in storm runoff, a PCR-restriction fragment length polymorphism technique based on the small-subunit rRNA gene was used in the analysis of 94 storm water samples collected from the Malcolm Brook and N5 stream basins in New York over a 3-year period. The distribution of Cryptosporidium in this study was compared with the data obtained from 27 storm water samples from the Ashokan Brook in a previous study. These three watersheds represented different levels of human activity. Among the total of 121 samples analyzed from the three watersheds, 107 were PCR positive, 101 of which (94.4%) were linked to animal sources. In addition, C. hominis (W14) was detected in six samples collected from the Malcolm Brook over a 2-week period. Altogether, 22 Cryptosporidium species or genotypes were found in storm water samples from these three watersheds, only 11 of which could be attributed to known species/groups of animals. Several Cryptosporidium spp. were commonly found in these three watersheds, including the W1 genotype from an unknown animal source, the W4 genotype from deer, and the W7 genotype from muskrats. Some genotypes were found only in a particular watershed. Aliquots of 113 samples were also analyzed by the Environmental Protection Agency (EPA) Method 1623; 63 samples (55.7%) were positive for Cryptosporidium by microscopy, and 39 (78%) of the 50 microscopy-negative samples were positive by PCR. Results of this study demonstrate that molecular techniques can complement traditional detection methods by providing information on the source of contamination and the human-infective potential of Cryptosporidium oocysts found in water.
Optic nerve oxygen tension in pigs and the effect of carbonic anhydrase inhibitors.

PURPOSE To evaluate how the oxygen tension of the optic nerve (ONP(O)2) is affected by the administration of the carbonic anhydrase inhibitors dorzolamide and acetazolamide and by alterations in oxygen and carbon dioxide in the breathing mixture. METHODS Polarographic oxygen electrodes were placed in the vitreous humor immediately over the optic disc in 20 anesthetized pigs. Blood gasses and cardiovascular physiology were monitored. ONP(O)2 was recorded continuously with breathing gasses of 21% O2-79% N2, 100% O2, 20% O2-80% N2, and 5.19% CO2-19.9%, O2-74.9% N2. Acetazolamide (15-1000 mg) and dorzolamide (6-1000 mg) were administered intravenously. RESULTS The mean (+/- SD) ONP(O)2 was found to be 24.1+/-11.6 mm Hg when the pigs were breathing room air and 50.7+/-29.3 mm Hg when they were breathing 100% O2 (n = 15; P < 0.001). In response to breathing 5.19% CO2, ONP(O)2 changed from 20.8+/-5.6 mm Hg (with 20.0% O2) to 28.9+/-3.6 mm Hg (n = 4; P < 0.001). Intravenous injections of 500 mg dorzolamide increased ONP(O)2 from 16.4+/-6.1 mm Hg to 26.9+/-12.2 mm Hg, or 52.5%+/-21.2% (n = 5; P = 0.017). A dose-dependent effect on ONP(O)2 was seen with intravenous dorzolamide doses of 1000, 500, 250, 125, 63, 27, 15, and 6 mg. Intravenous injections of 500 mg acetazolamide increased ONP(O)2 from 23.6+/-9.5 mm Hg to 30.9+/-10.0 mm Hg (n = 6; P < 0.001), and a dose-dependent effect was seen with doses of 1000, 500, 250, 125, 31, and 15 mg. CONCLUSIONS ONP(O)2 is significantly increased by the carbonic anhydrase inhibition of dorzolamide and acetazolamide, and the effect is dose dependent. These data demonstrate for the first time a direct effect of carbonic anhydrase inhibitors on ONP(O)2.
Increases in cyclic 3′,5′‐guanosine monophosphate (cGMP) occur at ecdysis in an evolutionarily conserved crustacean cardioactive peptide‐immunoreactive insect neuronal network

At the end of each instar, insects shed their old cuticle by performing the stereotyped ecdysis behavior. In the moth, Manduca sexta, larval ecdysis is accompanied by increases in intracellular cyclic 3′,5′‐guanosine monophosphate (cGMP) in a small network of 50 peptidergic neurons within the ventral central nervous system (CNS). Studies on a variety of insects show that this cGMP response has been associated with ecdysis throughout most of insect evolution. In the mealbeetle (Tenebrio, Coleoptera) and the mosquito (Aedes, Diptera), all 50 neurons showed increases in cGMP immunoreactivity (‐IR) at ecdysis, and all were immunopositive for crustacean cardioactive peptide (CCAP). Other insects varied with respect to their cGMP response at ecdysis and their CCAP‐IR. In more primitive insects, such as the silverfish (Ctenolepisma, Zygentoma) and the grasshopper (Locusta, Orthoptera), an abdominal subset of these neurons did not show detectable cGMP‐IR at ecdysis, although the neurons were CCAP‐IR. Conversely, whereas CCAP‐IR was severely reduced in the thoracic and subesophageal neurons of Lepidoptera larvae and may be absent in a subset of the corresponding abdominal neurons in crickets (Gryllus, Orthoptera), the ecdysial cGMP response occurred in all 50 neurons. The most extreme case was found in cyclorrhaphous flies, in which most of the 50 neurons were CCAP‐IR, although none showed increases in cGMP at ecdysis. This situation in higher Diptera is discussed in terms of their highly modified ecdysis behaviors. © 1996 Wiley‐Liss, Inc.
Negative Influence of Gammarinema gammari (Nematoda) on the Fecundity of Microphallus papillorobustus (Trematoda): Field and Experimental Evidence

The gammarid amphipod Gammarus insensibilis frequently harbors adult individuals of the ectoparasitic nematode Gammarinema gammari as well as metacercariae of the trematode Microphallus papillorobustus. After the demonstration in a previous study of a negative relationship between the abundance of these 2 parasites, the nature of the relationship between these 2 parasites was explored in more detail by studying, in the field and in the laboratory, the influence of nematode abundance on trematode fecundity. In gammarids collected in the field, a negative relationship between metacercarial fecundity and the number of co-occurring nematodes was found. By manipulating the nematode abundance in the laboratory, it was confirmed that G. gammari has a negative effect on egg production in M. papillorobustus.
Blood pressure, perfusion pressure, and open-angle glaucoma: the Los Angeles Latino Eye Study.

PURPOSE To examine the cross-sectional relationship between blood pressure, perfusion pressure, and prevalence of open angle glaucoma (OAG) in an adult Latino population. METHODS Participants aged 40 years and older (N = 6130) from the Los Angeles Latino Eye Study (LALES), a large, population-based study of self-identified adult Latinos, underwent an interviewer-administered questionnaire and a complete ocular and clinical examination. Logistic regression was used to evaluate the covariate-adjusted association of OAG with systolic, diastolic, and mean blood pressures and perfusion pressures. Covariates included age, intraocular pressure, history of glaucoma treatment including medications and surgery, and history of blood pressure and treatment of blood pressure including use of medications. RESULTS Low systolic (odds ratio [OR] = 2.5), diastolic (OR = 1.9), and mean (OR = 3.6) perfusion pressures and low diastolic blood pressure (OR = 1.9) were associated with a higher prevalence of OAG in LALES participants. Higher systolic blood pressure and mean arterial blood pressure were associated with a higher prevalence of OAG. There was no relationship between the prevalence of OAG and the presence of a history of cardiovascular disease. CONCLUSIONS Low diastolic, systolic and mean perfusion pressures, low diastolic blood pressure, and high systolic and mean arterial blood pressures are associated with a higher prevalence of OAG in adult Latinos.
A randomized controlled trial of endoscopie variceal band ligation for primary prophylaxis of variceal bleeding

Objective: To assess the efficacy and safety of endoscopie variceal band ligation (EVL) for primary prophylaxis of variceal bleeding in patients with high-risk varices. Design: A randomized, controlled trial. Setting: Hospital based. Subjects: Sixty-eight patients with portal hypertension with high-risk varices were randomized to undergo either EVL (n=35) or no treatment (n=33). Interventions: Endoscopie variceal band ligation or no therapy. Main outcome measures: Probability of first variceal bleeding, probability of survival, variceal obliteration, complications of EVL. Results: Oesophageal varices could be obliterated by EVL in 3.2 ±1.2 sessions within 4.9±2.2 weeks. Three (8.6%) patients in the EVL group and 13 (39.4%) in the control group bled during a mean follow-up of 14.1 ±5.0 months (range 2–22) (P<0.01). The cumulative probability of the patients remaining free of bleeding was higher (P< 0.01) in the EVL group than the control. Variceal recurrence was seen in 10 (28.6%) patients and was managed by repeated EVL. None of the patients developed oesophageal stricture. Four (11.4%) patients in the EVL and eight (24.2%) in the control group died (P=NS). Bleed-related mortality was lower in the EVL than the control group (2.9%vs. 15.2%, P=0.08) Conclusion: EVL significantly decreases the frequency of first variceal bleed. It should be evaluated further to see if bleeding-related mortality could be reduced in cirrhotics with high-risk varices who have not bled.
Sexually transmitted diseases and human immunodeficiency virus control in Malawi: a field study of genital ulcer disease.

Men with genital ulcer disease (GUD) attending a clinic in Malawi were evaluated and treated with one of five drug regimens. Haemophilus ducreyi was isolated from 204 (26.2%) of 778 patients. Of 677 men, 198 (29.2%) had treponemes detected in ulcer material by direct immunofluorescence or had rapid plasma reagin reactivity of > or = 1:8. Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 58.9% overall and 75.8% among patients reporting a history of GUD (P < .001). By logistic regression analysis, HIV-1 seropositivity was shown to impair ulcer healing (P = .003). Treatment failure rates for culture-proven chancroid were 19% for trimethoprim-sulfamethoxazole, 12.9% and 7.4%, respectively, for low- and high-dose erythromycin regimens, and 8.3% and 0, respectively, for low- and high-dose ciprofloxacin regimens. Herpes antigen was detected by EIA in 6 (23.1%) of 26 nonhealing ulcers. In Malawi, GUD should be managed as a syndrome to assure treatment of both syphilis and chancroid.
A growing family: Adding mutated Erbb4 as a novel cancer target

As the upward spiral of novel cancer gene discoveries and novel molecular compounds continues to accelerate, a repetitive theme in molecular drug development remains the lack of activity of initially promising agents when given to patients in clinical trials. It is however invigorating that a few targeted agents directed against a select group of a few ‘cancer gene superfamilies’ have escaped this all to common fate, and have evolved into novel, clinically meaningful molecular therapy strategies. Targeting dysregulated signaling of the epidermal growth factor family of transmembrane receptors (Erbb family) has encompassed over the last decade an ever increasing role in personalized treatment approaches in an increasing number of human malignancies. Erbbs are receptor tyrosine kinases that are important regulators of several signaling pathways. Two of its family members (Erbb1/EGFR and Erbb2/HER2) have previously been shown to be somatically mutated in large fraction of human cancers. To determine if this family is somatically mutated in melanoma, its sequences were recently analyzed and one of its members, Erbb4, was found to be somatically mutated in 19% of melanoma cases. Functional analysis of seven of its mutations was shown to increase its catalytic and transformation abilities as well as providing essential survival signals. Similar to other Erbb family members, mutant Erbb4 seems to confer ‘oncogene addiction’ on melanoma cells, making it an attractive therapeutic target. Gaining further understanding into the oncogenic mechanism of Erbb4 may not only help in the development of targeted therapy in melanoma patients but might accelerate the acceptance of a novel taxonomy of cancer which is based on the genomic perturbations in cancer genes and cancer gene families and their response to targeted agents.