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PubMed2025

Imidazole propionate is a driver and therapeutic target in atherosclerosis.

Atherosclerosis is the main underlying cause of cardiovascular diseases. Its prevention is based on the detection and treatment of traditional cardiovascular risk factors1. However, individuals at risk for early vascular disease often remain unidentified2. Recent research has identified new molecules in the pathophysiology of atherosclerosis3, highlighting the need for alternative disease biomarkers and therapeutic targets to improve early diagnosis and therapy efficacy. Here, we observed that imidazole propionate (ImP), produced by microorganisms, is associated with the extent of atherosclerosis in mice and in two independent human cohorts. Furthermore, ImP administration to atherosclerosis-prone mice fed with chow diet was sufficient to induce atherosclerosis without altering the lipid profile, and was linked to activation of both systemic and local innate and adaptive immunity and inflammation. Specifically, we found that ImP caused atherosclerosis through the imidazoline-1 receptor (I1R, also known as nischarin) in myeloid cells. Blocking this ImP-I1R axis inhibited the development of atherosclerosis induced by ImP or high-cholesterol diet in mice. Identification of the strong association of ImP with active atherosclerosis and the contribution of the ImP-I1R axis to disease progression opens new avenues for improving the early diagnosis and personalized therapy of atherosclerosis.

Atherosclerosis↗
PubMed2003

Prevalence of erectile dysfunction and its correlates among men attending primary care clinics in three countries: Pakistan, Egypt, and Nigeria.

The prevalence and correlates of erectile dysfunction (ED) in developing countries are largely unknown. Our objectives were to determine the prevalence and associated factors of ED in three countries (Pakistan, Egypt, Nigeria) that represent very different cultures. Men 35-70y of age seeking primary medical care answered a structured questionnaire adapted to reflect local cultures. Degree of ED was categorized as 'none,' 'mild,' 'moderate,' or 'complete.' The age-adjusted prevalence rates of ED among men attending primary care clinics was 57.4% in Nigeria, 63.6% in Egypt, and 80.8% in Pakistan. Older age, diabetes, peptic ulcers, prostate disease, depression-related symptoms, and caffeine consumption were independently associated with increased prevalence of ED, whereas being moderately active to very active at work (hard physical labor) and during leisure time (strenuous exercise) was associated with half the prevalence of moderate-to-complete ED. Our multicultural study demonstrates that in every country studied, high proportions of men older than age 35 have some degree of ED (57-81%). Both severity and prevalence increase consistently with age. Factors associated with ED are similar, but their distribution differs across countries.

Adult↗
PubMed2003

Low awareness of intestinal schistosomiasis in northern Senegal after 7 years of health education as part of intense control and research activities.

We evaluated the awareness of and knowledge about intestinal schistosomiasis in a highly infected rural community of northern Senegal where a variety of health information and education activities had taken place for 7 years as a component of different research and control programmes. As the infection had been introduced only recently, an initial 'zero' knowledge can be assumed. Most of the health education activities had been performed with adapted messages through local health and community workers. By a questionnaire, 566 individuals were asked simple questions on symptoms, mode of transmission, the sources of information and health-seeking behaviour. About 86% of the respondents stated that they knew what schistosomiasis was, and 92% that in case of illness they would seek treatment at the health centre. However, only half of the people accurately quoted symptoms associated with intestinal schistosomiasis: diarrhoea, abdominal pain and bloody stools. The majority of respondents realized that the disease was somehow linked with water and (lack of) hygiene, but only 44% of respondents reported water contact as the source of infection. Ultimately, only 30% of the respondents gave adequate answers about both symptoms and mode of transmission. We conclude that even intense and long-lasting education efforts for a specific and straightforward problem as schistosomiasis are not enough to have profound impact on the knowledge of rural traditional communities.

Adult↗
PubMed1998

Regulation of immune responses at mucosal surfaces: allergic respiratory disease as a paradigm.

The epithelial surfaces of the respiratory tract represent a fragile interface between the immune system and the outside environment. In order to maintain local homeostasis, the adaptive immune system must continuously discriminate between innocuous antigens which are ubiquitous in the atmosphere, and antigens associated with microbial pathogens. Any breakdown in this discrimination process can potentially lead to chronic inflammatory disease. The mechanisms employed by the mucosal immune system to maintain this delicate balance are many and varied, and a comprehensive understanding of how they collectively operate would provide novel insight into a wide variety of diseases. This discussion reviews recent progress in this area, focusing on allergic respiratory disease as a model for the study of immune regulation at mucosal surfaces.

Animals↗
PubMed1982

Fibrinogen-fibrin conversion and inhibition of fibrinolysis.

The fibrin adhesion technique is the imitation of the last step of the coagulation system. Fibrinogen is converted by thrombin into fibrin and stabilized by factor XIII. Fibrin sticks to the tissue and the tissue is adapted by syneresis. Local application of aprotinin to the thrombin solution is necessary in order to inhibit premature lysis of the fibrin film. This technique is now used in some selected cases in man such as fixation of cartilage, tendon, sealing of colonic anastomoses and preclotting of vessel grafts. An excellent hemostyptic effect of the fibrin glue in combination with absorbable collagen tampons was found. This combination technique is now used to seal parenchymatous organs and to stop hemorrhage in patients with defective hemostasis particularly those undergoing open heart surgery.

Animals↗
PubMedDate not supplied

[Experimental results of stepped titanium shafts for hip endoprostheses].

Among the materials which can be used for hip prostheses to be implanted without bone cement, ceramics and titanium possess the best overall properties for insuring long-term stability in the light of present knowledge. However, considered separately, the two materials are most suitable for different special requirements. Results of long-term animal experiments conducted by different working groups on functionally stressed hip and tooth-root implants made of bio-inert Al2O3 ceramic and titanium have furnished knowledge of the possibilities and limitations of the adaptation reaction of the bone tissue. The present authors investigated whether, by combining Al2O3 ceramic and titanium, a cement-free total hip replacement can be adapted to specific local stresses, taking biomechanical rules and anatomical factors into account. In recent experimental series it proved possible to limit the problems which had occurred in previous series, reported elsewhere. Positive results in dogs led to a human implant which has so far been used 15 times, with Al2O3 (FRIALIT) acetabula and heads, which have been implanted successfully for a number of years, in combination with the new stepped titanium shaft. In addition to a short review of follow-up findings thus far, the results of the experimental investigations are presented.

Animals↗
PubMed1999

Physical and histologic properties of substitutes used for the anterior fossa region dural repair.

During the last 10 years, 41 patients with dural tear caused by anterior cranial fossa bone fracture were treated surgically. Those treated conservatively were not included in this series. The patients' mean age was 36 years. The average time of postoperative observation was 15 months. Traffic accidents, as well as wounds caused by missiles (shell fragments or bullets), blows, and falls were the mechanisms of injury. An autogenous graft, followed by homologous (lyodura) and most recently by heterologous (lyoplant; B. Braun Melsungen AG, Melsungen, Germany) implants, was used to repair the dural lacerations. Fibrin adhesive was used to seal the sutures inserted between graft and dural defect margins in a majority of cases. The following criteria are required for the best dural substitute: uncontaminated tissue, histologic similarity to the local dura mater, adaptability, quick rehidratation, waterproof closure and the dural margins fast healing, and tensile strength easily resisting cerebrospinal fluid pressurization in physiological and pathological conditions. To define the effects of different tissue that could meet the above-mentioned criteria, we have undertaken a mechanical testing of the dural substitutes' tensile strength followed by histologic examination, and comparison with the dura mater of the anterior fossa region. Finally, we have paid particular attention to the clinical results of these substitutes.

Journal Article↗
PubMed2000

Localization of messenger ribonucleic acid for adrenomedullin and adrenomedullin receptor in the human placenta in normal pregnancies and pregnancies complicated by oligohydramnios.

OBJECTIVE: The purpose of this study was to identify the placental expression of adrenomedullin and adrenomedullin receptor messenger ribonucleic acid and compare them between placentas from pregnancies associated with oligohydramnios as a result of uteroplacental insufficiency and placentas from normal pregnancies. STUDY DESIGN: Total ribonucleic acid was extracted from the amnion, chorion, cotyledon, umbilical vein, and umbilical artery in 5 normal placentas and 3 placentas from pregnancies complicated by oligohydramnios. A cell line known to express messenger ribonucleic acid of adrenomedullin and its receptor was used to optimize the polymerase chain reaction and served as a positive control preparation in all experiments. Semiquantitative reverse transcriptase-polymerase chain reaction results for adrenomedullin and adrenomedullin receptor were compared between tissues as densitometric ratios of adrenomedullin or adrenomedullin receptor messenger ribonucleic acid to beta(2)-microglobulin messenger ribonucleic acid. Results were analyzed with a Kruskal-Wallis 1-way analysis of variance. Immunohistochemical staining with an antibody to human adrenomedullin was used to localize adrenomedullin in all tissue types. RESULTS: Messenger ribonucleic acid sequences for adrenomedullin and adrenomedullin receptor genes were identified in all tested placental tissue components. Within the normal placentas the expressions of adrenomedullin and adrenomedullin receptor messenger ribonucleic acid sequences did not differ statistically between the tissue components. Within placentas from patients with oligohydramnios the expressions of adrenomedullin and adrenomedullin receptor messenger ribonucleic acid did not differ statistically between the tissue components. When normal placentas were compared with placentas from pregnancies complicated by oligohydramnios, however, a 5-fold increase in adrenomedullin messenger ribonucleic acid and a 3-fold increase in adrenomedullin receptor messenger ribonucleic acid were seen in placentas from patients with oligohydramnios. Adrenomedullin immunoreactivity was present in all tissues studied. CONCLUSION: The expression of messenger ribonucleic acid for both adrenomedullin and its receptor in these tissue components implies that placental tissues function in both synthesis and action of adrenomedullin. The increased adrenomedullin messenger ribonucleic acid expression in the umbilical artery and the elevated adrenomedullin receptor messenger ribonucleic acid expression in the cotyledons of placentas from patients with oligohydramnios may represent a local fetoplacental physiologic adaptive response to vascular compromise.

Adrenomedullin↗
PubMed2003

Lateral functional shift of the mandible: Part I. Effects on condylar cartilage thickness and proliferation.

Lateral functional shift of the mandible is characterized by transverse rotation of the entire mandible about a vertical axis toward 1 side of the head. The effect of this shift is that the condyle on the side opposite the direction of the shift is displaced anteriorly, or protruded, while the condyle on the side toward the shift is more stable positionally and is likely to be slightly retruded. According to the view that growth of the mandibular condylar cartilage (MCC) adapts to its local functional-biomechanical environment, differential changes in metabolic activity of the MCC would be expected on the nonprotruded and the protruded sides. To evaluate this hypothesis, 21 rats (28 days old) were fitted with intraoral positioners designed to shift the mandibular postural position asymmetrically. Cartilage thickness and BrdU labeling index in the MCC 3, 7, and 14 days after placement of the positioners were compared with those in age-matched controls that received no positioners. Cartilage thickness in the MCC on the protruded side was significantly greater than that in the controls at each time interval, with the difference increasing slightly with time. The labeling index for the protruded MCC was significantly greater than the controls at both 7 and 14 days after positioner placement. Trends on the nonprotruded side were generally opposite, culminating in reduced thickness and proliferation after 14 days. Thickness and labeling index were greater on the protruded side at every time interval except 3 days (labeling index). These trends in cartilage thickness and proliferation are consistent with previous studies of MCC changes after bilateral functional protrusion or retrusion. These data suggest that changes in MCC thickness and proliferative activity might accompany a lateral functional shift of the mandible in growing persons.

Analysis of Variance↗
PubMed2001

Improving clinical management for consumers with co-existing mental health and substance use disorders: an integrated approach.

Using Quality Improvement project methodology, complex organisational and clinical practice change was brought about to improve services for people with co-existing mental health and alcohol and drug misuse. The project describes local uptake and adaptation of national and state policy to achieve change that is sustainable within existing resources. Emphasis on engagement of staff and consumers and carers throughout the change was an essential component. The project has implications for the introduction of changes in response to other national policy directives.

Diagnosis, Dual (Psychiatry)↗
PubMed2001

GSA11 encodes a unique 208-kDa protein required for pexophagy and autophagy in Pichia pastoris.

Cells are capable of adapting to changes in their environment by synthesizing needed proteins and degrading superfluous ones. Pichia pastoris synthesizes peroxisomal enzymes to grow in methanol medium. Upon adapting from methanol medium to one containing glucose, this yeast rapidly and selectively degrades peroxisomes by an autophagic process referred to as pexophagy. In this study, we have utilized a novel approach to identify genes required for this degradative pathway. Our approach involves the random integration of a vector containing the Zeocin resistance gene into the yeast genome by restriction enzyme-mediated integration. Cells unable to degrade peroxisomes during glucose adaptation were isolated, and the genes that were disrupted by the insertion of the vector were determined by sequencing. By using this approach, we have identified a number of genes required for glucose-induced selective autophagy of peroxisomes (GSA genes). We report here the characterization of Gsa11, a unique 208-kDa protein. We found that this protein is required for glucose-induced pexophagy and starvation-induced autophagy. Gsa11 is a cytosolic protein that becomes associated with one or more structures situated near the vacuole during glucose adaptation. The punctate localization of Gsa11 was not observed in gsa10, gsa12, gsa14, and gsa19 mutants. We have previously shown that Gsa9 appears to relocate from a compartment at the vacuole surface to regions between the vacuole and the peroxisomes being sequestered. In the gsa11 mutants, the vacuole only partially surrounded the peroxisomes, but Gsa9 was still distributed around the peroxisome cluster. This suggests that Gsa9 binds to the peroxisomes independent of the vacuole. The data also indicate that Gsa11 is not necessary for Gsa9 to interact with peroxisomes but acts at an intermediate event required for the vacuole to engulf the peroxisomes.

Amino Acid Sequence↗
PubMed1996

Economic advantage and the cognitive ability of rural children in Zaire.

Rural Zairian children (n = 32), 4 to 6 years old, were enrolled in a preschool educational and nutritional enrichment program throughout the school year. As part of the evaluative research for this program, cognitive and motor development of the children was assessed with the American Guidance Service (AGS) Early Childhood Screening Profiles (ECSP; Harrison et al., 1990) battery, adapted to the local Bantu dialect of Kituba. On the ECSP global indicator of cognitive ability, the children in the enrichment program performed significantly better than their counterparts in nearby villages, although the two groups did not differ significantly on motor development or anthropometric indicators of physical development. The results indicate that rural African children with reasonable nutritional status demonstrate significantly improved intellectual development in response to a comprehensive economic enhancement and educational enrichment program for them and their families.

Child↗
PubMed2000

Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14.

Little is known about innate immunity to bacteria after birth in the hitherto sterile fetal intestine. Breast-feeding has long been associated with a lower incidence of gastrointestinal infections and inflammatory and allergic diseases. We found in human breast milk a 48-kD polypeptide, which we confirmed by mass spectrometry and sequencing to be a soluble form of the bacterial pattern recognition receptor CD14 (sCD14). Milk sCD14 (m-sCD14) concentrations were up to 20-fold higher than serum sCD14 from nonpregnant, pregnant, or lactating women. In contrast, lipopolysaccharide (LPS)-binding protein was at very low levels. Mammary epithelial cells produced 48-kD sCD14. m-sCD14 mediated activation by LPS and whole bacteria of CD14 negative cells, including intestinal epithelial cells, resulting in release of innate immune response molecules. m-sCD14 was undetectable in the infant formulas and commercial (cows') milk tested, although it was present in bovine colostrum. These findings indicate a sentinel role for sCD14 in human milk during bacterial colonization of the gut, and suggest that m-sCD14 may be involved in modulating local innate and adaptive immune responses, thus controlling homeostasis in the neonatal intestine.

Amino Acid Sequence↗
PubMed2004

Allogeneic blood transfusions: benefit, risks and clinical indications in countries with a low or high human development index.

The risks associated with allogeneic red blood cell (RBC) transfusions differ significantly between countries with low and high human development indexes (HDIs). In countries with a low HDI, the risk of infection (HIV, HBV, HCV and malaria) is elevated. In contrast, in countries with a high HDI, immunological reactions (haemolytic transfusion reactions, alloimmunization and immunosuppression) are predominant. Therefore the overall risk associated with RBC transfusions in low HDI countries is much more significant than that in high HDI countries. In view of these risks, the limited efficacy of RBC transfusion and its high costs, this procedure should be used sparingly and rationally. Therefore RBC transfusion protocols adapted to the local situation are essential. Such protocols should distinguish between physiological and haemoglobin-based transfusion triggers. In countries with a high HDI, relative tachycardia and hypotension, despite normovolaemia, ST-segment changes suggestive of myocardial ischaemia and an Hb level <6 g/dl can serve as general guidelines for transfusion. Higher haemoglobin transfusion triggers should be used for patients aged >80 years and those with coronary artery or cerebrovascular disease. In countries with a low HDI, clinical signs of circulatory failure or myocardial ischaemia and an Hb level <5 g/dl can serve as transfusion guidelines.

Adult↗
PubMed2006

Visual area V5/MT remembers "what" but not "where".

Priming for motion direction has been shown to depend upon the functional integrity of extrastriate area V5/MT. Its retinotopic organization and the interactions recently found between motion adaptation and misperceived localization may suggest, for this area, a role for priming of spatial position in addition to the established priming of motion direction. Disruption of V5/MT with repetitive transcranial magnetic stimulation during the intertrial interval had the effect of abolishing priming of motion direction but no effect in priming of spatial position. These effects cannot be explained in terms of perception or task demands but only in terms of the effects of information irrelevant to the correct performance of the task stored over the intertrial interval. We suggest that the attribute of spatial position might be stored in short-term memory either in earlier areas of the motion pathways such as V3 or in higher cortical areas traditionally associated with the analysis of spatial information, for example, posterior parietal cortex or the frontal eye fields.

Adult↗
PubMed2006

Measurement and reporting of burden of disease for hepatitis A: results of the EUROHEP.NET feasibility survey.

BACKGROUND: European countries use a wide variety of surveillance systems and prevention measures for viral hepatitis. Each system is adapted to the local situation and an overview was never mapped out at European level. The EUROHEP.NET Project is a European Commission-funded feasibility study for a future network on surveillance and prevention of vaccine-preventable hepatitis. We analysed the measurement and reporting of burden of disease for hepatitis A (HA) and B (HB) in the participating countries. METHODS: Twenty-eight countries were invited to participate in this study. An online survey was available from the project's website (www.eurohep.net). The questions concerned the organisation of the surveillance system, case definition, burden of disease, epidemiology, and vaccination strategies. The responses on data sources and the numeric data related to burden of disease for HA for the period 1997-2001 were analysed. RESULTS: Twenty-two countries completed the survey for hepatitis A. Data on total number of hospitalisations and deaths were available from 17 and 18 countries, respectively, although sometimes not complete. Data on hospitalisation days, number of liver transplants and proportion of these due to HAV were often not available. CONCLUSION: Surveillance systems on burden of disease for hepatitis A show a wide diversity among the participating countries. The introduction of a standardised system of data collection at the European Union level according to ICD-10 but respecting the local current practices is a primary need, especially for data that should be collected in all countries, like hospitalisation and mortality. A link to surveillance databases is also strongly recommended.

Adolescent↗
PubMed1992

Associations between nuclear loci and chloroplast DNA genotypes in wild barley.

Associations among alleles at nine nuclear loci and three chloroplast DNA (cpDNA) genotypes were assessed in a sample of 247 accessions of the wild barley, Hordeum vulgare ssp. spontaneum. Alleles at two of the nine nuclear loci are marked by length variations in the intergenic spacer region of ribosomal DNA (rDNA), and those of the other seven loci are well characterized allozymes. The three chloroplast DNA (cpDNA) genotypes are marked by restriction fragment length polymorphisms resulting from three polymorphic restriction sites detected by Southern blot hybridization. The analyses were performed by dividing the nine nuclear loci into a series of two-locus subsets and constructing log-linear models to characterize associations between the subsets of two nuclear loci and the cpDNA genotypes. Statistically significant associations were detected between six of the nine nuclear loci and the cpDNA genotypes, either individually as pairwise correlations, or through interaction with another nuclear locus to form three-variate complexes. Although the sample size of the present study was inadequate for statistical evaluation of higher order interactions, the results suggest the existence of interactions in which more than two nuclear loci are involved in associations with cpDNA genotypes. The observed cytonuclear associations appear to result from interplay among a number of evolutionary forces including a mating system of predominant selfing, differentiation among gene pools of local populations, and adaptation of barley genotypes to specific environmental conditions.

Blotting, Southern↗
PubMed2003

Immunocompetent cells in the endometrium of fetuses and children.

BACKGROUND: Although the immunocompetent cells of the adult human endometrium are well characterized, there is little information about these cells in the developing uterus. This study was undertaken to investigate the distribution of leukocyte subpopulations in the endometrium of fetuses and children. METHODS: Uterine tissue obtained at autopsy from fetuses (n = 11) and neonates/children (n = 9) between 17 weeks gestation and 5(1/2) years of age was investigated with antibodies against various leukocyte subsets by immunohistochemical staining techniques. RESULTS: The densities of CD45+ and CD68+ cells were significantly higher in the endometrium of neonates/children than in that of fetuses. CD14+ monocytes represented the largest leukocyte subpopulation in both groups. CD56+ natural killer cells and HLA-DR+ antigen-presenting cells were absent from fetal endometrium. There were no differences in density of CD3+ T cells between the two groups, but CD4+ T helper cells were found only in fetal endometrium. CONCLUSIONS: The endometrial leukocyte population of fetuses and small children is different from that seen in adult women. The appearance of CD56+ and HLA-DR+ cells in endometrium seems to be a post-natal event, which may be induced by the changes in hormone levels and/or the adaptation of the local immune system to the changing microenvironment.

Antigen-Presenting Cells↗