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Normal Humans (normal + human)
Terms modified by Normal Humans Selected AbstractsCarbohydrate expression and modification during keratinocyte differentiation in normal human and reconstructed epidermisEXPERIMENTAL DERMATOLOGY, Issue 5 2003Bruno Méhul Abstract:, Using fluorescein isothiocyanate (FITC)-labeled lectins we were able to demonstrate the presence of specific carbohydrate moieties in normal human and reconstructed epidermis. Evidence is provided that in both cases the strongly reduced lectin staining at the level of the stratum corneum is the result of a hindered accessibility of the lectins in this lipid-rich hydrophobic environment. Isolated corneocytes and purified cornified envelopes (CEs) exhibited clearly glycosylated structures reacting with distinct lectins. The presence of glycosidase activity, particularly in the upper layers of the epidermis characterized by an acidic environment (pH 5.5), indicates that modifications of the sugar residues might be important in epidermal homeostasis, barrier behavior and desquamation. Absent or strongly reduced glycosidase activity in the stratum corneum of reconstructed epidermis with an impaired pH gradient could be in part responsible for the reduced barrier function and the lack of desquamation in this model. [source] Role of anti-,-glucan antibody in host defense against fungiFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2005Ken-ichi Ishibashi Abstract We have recently detected an anti-,-glucan antibody in normal human and normal mouse sera. The anti-,-glucan antibody showed reactivity to pathogenic fungal Aspergillus and Candida cell wall glucan. Anti-,-glucan antibody could bind whole Candida cells. It also enhanced the candidacidal activity of macrophages in vitro. The anti-,-glucan antibody titer of DBA/2 mice intravenously administered either Candida or Aspergillus solubilized cell wall ,-glucan decreased remarkably dependent on dose. Moreover, in deep mycosis patients, the anti-,-glucan antibody titer decreased, and this change correlated with clinical symptoms and other parameters such as C-reactive protein. It was suggested that the anti-,-glucan antibody formed an antigen,antibody complex and participated in the immune response as a molecule recognizing pathogenic fungi. [source] Rac and Rho: The Story Behind Melanocyte Dendrite FormationPIGMENT CELL & MELANOMA RESEARCH, Issue 5 2002Glynis Scott Melanocyte dendrites are hormonally responsive actin and microtubule containing structures whose primary purpose is to transport melanosomes to the dendrite tip. Melanocyte dendrites have been an area of intense interest for melanocyte biologists, but it was not until recently that we began to understand the mechanisms underlying their formation. In contrast with melanogenesis, for which numerous mutations in pigment producing genes and mouse models have been identified, a genetic defect resulting in impaired dendrite formation has not been found. Therefore, much of the insight into melanocyte dendrites has come from electron microscopy or in vitro culture systems of normal human and murine melanocytes as well as melanoma cell lines. The growth factors that regulate the formation of melanocyte dendrites have been thoroughly studied and it is clear that multiple signalling systems are able to stimulate, and in some cases inhibit, dendrite formation. Recent data points to the Rho family of small guanosine triphosphate (GTP)-binding proteins as master regulators of dendrite formation, particularly Rac and Rho. In this review I will summarize the progress scientists have made in understanding the structure, hormonal regulation and molecular mediators of melanocyte dendrite formation. [source] A Novel Gene "Niban" Upregulated in Renal Carcinogenesis: Cloning by the cDNA-amplified Fragment Length Polymorphism ApproachCANCER SCIENCE, Issue 9 2000Shuichi Majima A modified AFLP (amplified fragment length polymorphism) method was employed to isolate genes differentially expressed in renal carcinogenesis of Tsc2 gene mutant (Eker) rats. One gene, selected for further investigation, was named "Niban" ("second" in Japanese), because it is the second new gene to be found after Erc (expressed in renal carcinoma) in our laboratory. Importantly, "Niban" is well expressed even in small primary rat Eker renal tumors, more than in progressed cell lines, and is also expressed in human renal carcinoma cells, but not in normal human or rat kidneys. Chromosome assignment was to RNO 13 in the rat, and HSA 1. This "Niban" gene is a candidate as a marker for renal tumor, especially early-stage renal carcinogenesis. [source] Systemic nitric oxide clamping in normal humans guided by total peripheral resistanceACTA PHYSIOLOGICA, Issue 2 2010J. A. Simonsen Abstract Aim:, We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels. Methods:, Normal volunteers (23,28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor NG -nitro- l -arginine methyl ester (l -NAME) at 0.5 mg kg,1 h,1. One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l -NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography. Results:,l -NAME increased MABP and total peripheral resistance (TPR, 1.02 ± 0.05 to 1.36 ± 0.07 mmHg s mL,1, mean ± SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 ± 0.05 mmHg s mL,1, P < 0.05). CO decreased with l -NAME (5.8 ± 0.3 to 4.7 ± 0.3 L min,1, P < 0.01) and returned to control when SNP was added (6.0 ± 0.3 L min,1). A decrease in plasma noradrenaline (42%, P < 0.01) during l -NAME administration was completely reversed by SNP. Plasma renin activity decreased during l -NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l -NAME and remained elevated. Conclusions:, Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation. [source] Volume natriuresis vs. pressure natriuresisACTA PHYSIOLOGICA, Issue 4 2004P. Bie Abstract Body fluid regulation depends on regulation of renal excretion. This includes a fast vasopressin-mediated water-retaining mechanism, and slower, complex sodium-retaining systems dominated by the renin,angiotensin aldosterone cascade. The sensory mechanisms of sodium control are not identified; effectors may include renal arterial pressure, renal reflexes, extrarenal hormones and other regulatory factors. Since the pioneering work of Guyton more than three decades ago, pressure natriuresis has been in focus. Dissociations between sodium excretion and blood pressure are explained as conditions where regulatory performance exceeds the precision of the measurements. It is inherent to the concept, however, that sudden transition from low to high sodium intake elicits an arterial pressure increase, which is reversed by the pressure natriuresis mechanism. However, such transitions elicit parallel changes in extracellular fluid volume thereby activating volume receptors. Recently we studied the orchestration of sodium homeostasis by chronic and acute sodium loading in normal humans and trained dogs. Small increases in arterial blood pressure are easily generated by acute sodium loading, and dogs appear more sensitive than humans. However, with suitable loading procedures it is possible , also acutely , to augment renal sodium excretion by at least one order of magnitude without any change in arterial pressure whatsoever. Although pressure natriuresis is a powerful mechanism capable of overriding any other controller, it seems possible that it is not operative under normal conditions. Consequently, it is suggested that physiological control of sodium excretion is neurohumoral based on extracellular volume with neural control of renin system activity as an essential component. [source] Electroanatomic Analysis of Sinus Impulse Propagation in Normal Human AtriaJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2002ROBERTO DE PONTI M.D. Sinus Impulse Propagation in Normal Human Atria.Introduction: Better understanding of atrial propagation during sinus rhythm (SR) in normal hearts under the most normal physiologic conditions may be propaedeutic to pathophysiologic studies of complex atrial arrhythmias. In this study, qualitative and quantitative analyses of sinus impulse propagation in both atria were performed by electroanatomic mapping in patients with no organic heart disease who were undergoing an electrophysiologic procedure. Methods and Results: Seven patients (5 men and 2 women; age 37 ± 11 years) undergoing ablation of a left-sided accessory pathway were considered. Associated heart disease and coexisting atrial arrhythmias were excluded. After obtaining informed consent, electroanatomic mapping of both atria was performed during SR using a nonfluoroscopic system in the postablation phase. Mapping was accomplished in all patients with no complications. Qualitative analysis showed that sinus impulse propagation gives a reproducible activation pattern with minor individual variations. During interatrial propagation, two breakthroughs (anterior and posterior) in the left atrium are observed in the majority of cases. The anterior breakthrough, which reflects conduction over Bachmann's bundle, is predominant and shows a peculiar "preexcitation-like" endocardial activation pattern. Quantitative analysis showed minimal individual variations of propagation time intervals. Atria are activated simultaneously for 65% ± 9% of the duration of the atrial systolic time interval. Conclusion: In normal humans, electroanatomic mapping of SR identifies a typical and reproducible propagation pattern during SR. Bachmann's bundle plays the most important role in interatrial propagation. Atria are activated simultaneously by sinus impulse for a relevant portion of the systolic time interval. [source] Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005Akihito Ishigami Abstract Citrullinated proteins are the products of a posttranslational process in which arginine residues undergo modification into citrulline residues when catalyzed by peptidylarginine deiminases (PADs) in a calcium ion-dependent manner. In our previous report, PAD2 expressed mainly in the rat cerebrum became activated early in the neurodegenerative process. To elucidate the involvement of protein citrullination in human neuronal degeneration, we examined whether citrullinated proteins are produced during Alzheimer's disease (AD). By Western blot analysis with antimodified citrulline antibody, citrullinated proteins of varied molecular weights were detected in hippocampal tissues from patients with AD but not normal humans. Two of the citrullinated proteins were identified as vimentin and glial fibrillary acidic protein (GFAP) by using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. Interestingly, PAD2 was detected in hippocampal extracts from AD and normal brains, but the amount of PAD2 in the AD tissue was markedly greater. Histochemical analysis revealed citrullinated proteins throughout the hippocampus, especially in the dentate gyrus and stratum radiatum of CA1 and CA2 areas. However, no citrullinated proteins were detected in the normal hippocampus. PAD2 immunoreactivity was also ubiquitous throughout both the AD and the normal hippocampal areas. PAD2 enrichment coincided well with citrullinated protein positivity. Double immunofluorescence staining revealed that citrullinated protein- and PAD2-positive cells also coincided with GFAP-positive cells, but not all GFAP-positive cells were positive for PAD2. As with GFAP, which is an astrocyte-specific marker protein, PAD2 is distributed mainly in astrocytes. These collective results, the abnormal accumulation of citrullinated proteins and abnormal activation of PAD2 in hippocampi of patients with AD, strongly suggest that PAD has an important role in the onset and progression of AD and that citrullinated proteins may become a useful marker for human neurodegenerative diseases. © 2005 Wiley-Liss, Inc. [source] Effect of oral clarithromycin on gall-bladder motility in normal subjects and those with gall-stonesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2006S. SENGUPTA Summary Background Motilin receptor stimulation with erythromycin has been shown to have a prokinetic effect on gall-bladder motility in human beings. Aim To find out whether oral clarithromycin has similar prokinetic activity to erythromycin on fasting and postprandial gall-bladder emptying in normal humans and those with gall-stone disease. Methods In a blinded two-way crossover study clarithromycin 500 mg and a placebo were administered to 10 normal subjects and 10 subjects with gall-stone disease. Gall-bladder volumes were assessed in the fasting and postprandial state. Results Fasting volumes were significantly less following clarithromycin administration in both normal subjects and subjects with gall-stones compared with placebo (12.1 ± 1.8 mL vs. 17.8 ± 2.0 mL, P < 0.05 and 16.7 ± 2 mL vs. 26.8 ± 7.2 mL, P < 0.02, mean ± S.E.M). Postprandial volumes were also significantly less following clarithromycin administration. Ejection fraction significantly increased following clarithromycin in both normal subjects (66 ± 5.8% vs. 37 ± 5.9%, P = 0.02) and subjects with gall-stones (45 ± 3.2 vs. 20 ± 1.6%, P < 0.02). Conclusion Clarithromycin enhances both fasting and postprandial gall-bladder contraction in normal humans and also in those with gall-stone disease. [source] Motor unit recruitment during lengthening contractions of human wrist flexorsMUSCLE AND NERVE, Issue 11 2001Paula J. Stotz MSc Abstract The purpose of this study was to revisit the question of recruitment of motor units during lengthening contractions because of conflicting views in the literature on this subject. Motor unit activity was recorded from the flexor carpi radialis muscle of four human subjects to compare the patterns of recruitment during lengthening and isometric contractions. Lengthening contractions were produced either when the subject voluntarily stopped opposing a background load or when an additional load was imposed on the already contracting muscle. In both cases, lengthening of the active muscle was produced at a variety of speeds, from quite slow to "as fast as possible." No differences in recruitment order were observed between isometric and lengthening contractions at any speed of lengthening contraction. It is concluded that all contractions in normal humans recruit motor units in an orderly fashion from small to large, according to the size principle of motor unit recruitment. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1535,1541, 2001 [source] Repair of cyclobutyl pyrimidine dimers in human skin: variability among normal humans in nucleotide excision and in photorepairPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 3 2002Betsy M. Sutherland Background/Aims: Photoreactivation (PR) of cyclobutyl pyrimidine dimers (CPD) in human skin remains controversial. Recently Whitmore et al. (1) reported negative results of experiments using two photorepair light (PRL) sources on UV-irradiated skin of volunteers. However, their PRL sources induced substantial levels of dimers in skin, suggesting that the additional dimers formed could have obscured PR. We met a similar problem of dimer induction by a PRL source. We designed and validated a PRL source of sufficient intensity to catalyse PR, but that did not induce CPD, and used it to measure photorepair in human skin. Methods and Results: Using a solar simulator filtered with three types of UV-filters, we found significant dimer formation in skin, quantified by number average length analysis using electrophoretic gels of isolated skin DNA. To prevent scattered UV from reaching the skin, we interposed shields between the filters and skin, and showed that the UV-filtered/shielded solar simulator system did not induce damage in isolated DNA or in human skin. We exposed skin of seven healthy human volunteers to 302 nm radiation, then to the improved PRL source (control skin areas were kept in the dark for measurement of excision repair). Conclusions: Using a high intensity PRL source that did not induce dimers in skin, we found that three of seven subjects carried out rapid photorepair of dimers; two carried out moderate or slow dimer photorepair, and three did not show detectable photorepair. Excision repair was similarly variable in these volunteers. Subjects with slower excision repair showed rapid photorepair, whereas those with rapid excision generally showed little or no photoreactivation. [source] Antigenic Variation in Pneumocystis,THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 1 2007JAMES R. STRINGER ABSTRACT. Pneumocystis is a genus containing many species of non-culturable fungi, each of which infects a different mammalian host. Pneumonia caused by Pneumocystis is a problem in immunodeficient humans, but not in normal humans. Nevertheless, it appears that Pneumocystis organisms cannot survive and proliferate outside of their mammalian hosts, suggesting that Pneumocystis parasitizes immunocompetent mammals. Residence in immunocompetent hosts may rely on camouflage perpetrated by antigenic variation. In P. carinii, which is found in rats, there exist three families of genes that appear to be designed to create antigenic variation. One gene family, which encodes the major surface glycoprotein (MSG), contains nearly 100 members. Expression of the MSG family is controlled by restricting transcription to the one gene that is linked to a unique expression site. Changes in the sequence of the MSG gene linked to the expression site occur and appear to be caused by recombination with MSG genes not at the expression site. Preliminary evidence suggests that gene conversion is the predominant recombination mechanism. [source] Three Common Intronic Variants in the Maternal and Fetal Thiamine Pyrophosphokinase Gene (TPK1) are Associated with Birth WeightANNALS OF HUMAN GENETICS, Issue 5 2007D. Fradin Summary Extreme variations in birth weight increase immediate postnatal mortality and morbidity, and are also associated with the predisposition to metabolic diseases in late adulthood. Birth weight in humans is influenced by yet unknown genetic factors. Since the 7q34-q35 region showed linkage with birth weight in a recent human genome scan (p = 8.10,5), this study investigated the TPK1 (thiamine pyrophosphokinase) gene locus, located in 7q34-36. Having found no coding variants in the TPK1 gene, we genotyped 43 non coding SNPs spanning a region of 420kb, and used the QTDT method to test their association with birth weight in 964 individuals from 220 families of European ancestry. Family-based tests detected association of 8 SNPs with birth weight (p<0.008), but after correction for multiple tests only rs228581 C/T (p = 0.03), rs228582 A/G (p = 0.04) and rs228584 C/T (p = 0.03) were still associated with birth weight, as well as their T-A-T haplotype (p = 0.03). In addition, we found an association between maternal rs228584 genotype and offspring birth weight (p = 0.027). These observations suggest that genomic variations in the fetal and maternal TPK1 gene could contribute to the variability of birth weight in normal humans. [source] Levodopa: Faster and better word learning in normal humansANNALS OF NEUROLOGY, Issue 1 2004Stefan Knecht MD Dopamine is a potent modulator of learning and has been implicated in the encoding of stimulus salience. Repetition, however, as required for the acquisition and reacquisition of sensorimotor or cognitive skills (e.g., in aphasia therapy), decreases salience. We here tested whether increasing brain levels of dopamine during repetitive training improves learning success. Forty healthy humans took 100mg of the dopamine precursor levodopa or placebo daily for 5 days in a randomized double-blind and parallel-group design. Ninety minutes later on each day, subjects were trained on an artificial vocabulary using a high-frequency repetitive approach. Levodopa significantly enhanced the speed, overall success, and long-term retention of novel word learning in a dose-dependent manner. These findings indicate new ways to potentiate learning in a variety of domains if conventional training alone fails. [source] Species differences in bradykinin receptor-mediated responses of the airwaysAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2002K. M. Ellis Summary1 Bradykinin (BK) is a nine amino acid peptide (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) formed from the plasma precursor kininogen during inflammation and tissue injury. The actions of BK are mediated by G protein-coupled cell surface receptors, designated B1 and B2. 2 BK has a plethora of effects in the airways including bronchoconstriction, bronchodilation, stimulation of cholinergic and sensory nerves, mucus secretion, cough and oedema resulting from promotion of microvascular leakage. These airway effects are mediated in the main by the B2 receptor subtype. 3 BK acts mainly indirectly, primarily through airway nerve activation, but also by the release of prostanoids, thromboxanes and nitric oxide (NO). 4 Airway responses to BK have been studied in detail in guinea-pigs, mice, sheep and rats. This review describes the effects of BK in these species and draws comparison with its effects in normal humans and patients with respiratory diseases. 5 Despite its many and varied effects in the airways of animals and man, the exact contribution of BK to airways disease remains unclear. [source] The rate of apoptosis in post mitotic neutrophil precursors of normal and neutropenic humansCELL PROLIFERATION, Issue 1 2003M. C. Mackey Using data on the fraction of post-mitotic neutrophil precursors (CD15+ cells) displaying positive markers for apoptosis in 12 normal humans, and a simple mathematical model, we have estimated the apoptotic rate to be about 0.28/day in this compartment. This implies that the influx of myelocytes into the post-mitotic compartment exceeds twice the granulocyte turnover rate (GTR), and that about 55% of the cells entering this compartment die before being released into the blood. The normal half life of apoptotic post-mitotic neutrophil precursors is calculated to be 10.4 h. Comparable calculations for patients indicate apoptosis rates in the post-mitotic compartment of about 17 times normal for one myelokathexis patient and rates of about 13 times normal for the one cyclical neutropenic patient and two severe congenital neutropenic patients. The estimated half life for apoptotic post-mitotic neutrophil precursors in the myelokathexis patient was about 0.4 h, 1.4 h in the cyclical neutropenia patient, and about 0.6 h in the severe congenital neutropenic patients. [source] Circulating lymphocyte subsets linked to intracellular cytokine profiles in normal humansCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2003M. MATSUI SUMMARY To determine whether there is an association between intracellular cytokine profiles and the expression of surface antigens, we performed a simultaneous flow cytometric analysis of these laboratory parameters in 11 healthy volunteers. Peripheral blood lymphocytes were double-stained for CD4 or CD8, as well as CD11a, CD25, CD26, CD29 and CD45RA or the chemokine receptors CCR3, CCR4, CCR5 or CXCR3. Portions of the cell samples were cultured for 4 h in the presence of 1 µm monensin and 20 µg/ml brefeldin A with or without stimulation by phorbol myristate acetate plus ionomycin for the detection of intracellular interferon- , (IFN- ,), interleukin-2 (IL-2), tumour necrosis factor (TNF)- ,, and IL-4. As a result, CD4+CD29high helper inducer T cells were closely associated with IFN- , and TNF- , producing CD4+ cells, while CD4+CXCR3+ cells showed a negative correlation with IL-4-producing cells, suggesting that both of these CD4+ subsets consist mainly of Th1 cells. In contrast, CD4+CD45RA+ cells were correlated inversely with IFN- , and TNF- , -producing cells, and CD8+CD11ahigh killer effector and total CCR5+ cells showed an inverse correlation with IL-2 producing cells, suggesting an immunoregulatory role for these three subsets in non-pathological conditions. Therefore, monitoring of lymphocyte subsets that express functional surface antigens could provide additional information concerning immune deviation, as assessed by the production of Th1/Th2 type cytokines. Further, this type of combined study may provide clues for the pathogenesis of immune-mediated disorders. [source] Atorvastatin increases expression of low-density lipoprotein receptor mRNA in human circulating mononuclear cellsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2010Anothai Pocathikorn Summary 1.,3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, or statins, are commonly used to lower plasma cholesterol levels. HMGCR and the low-density lipoprotein (LDL) receptor (LDLR) are of central importance to cholesterol homeostasis and yet there is a paucity of data on the effect of statins on the regulation of the LDLR and HMGCR in humans. 2.,In the present study, we examined the effect of atorvastatin on the expression of HMGCR, LDLR and LDLR-related protein (LRP) mRNA in circulating mononuclear cells. Twelve human volunteers were treated with atorvastatin, 20 mg/day for 4 weeks. 3.,Atorvastatin decreased plasma total and LDL,cholesterol by 29% (P < 0.0001) and 41% (P < 0.001), respectively, and increased LDLR mRNA abundance, in absolute terms, by 35% (P < 0.001) and 31% (P < 0.0001) and 37% (P = 0.01) relative to reference GAPDH and ,-actin mRNA, respectively. In contrast, atorvastatin had no significant effect on LRP or HMGCR mRNA levels. 4. The increase in LDLR mRNA in circulating mononuclear cells agrees with the few human studies conducted, as well as with in vitro and animal studies, whereas the unchanged HMGCR mRNA is consistent with the hepatic specificity of atorvastatin. The present study firmly documents an increase in LDLR mRNA levels in response to statin administration in normal humans. [source] | |||||||||||||||||||||||||