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Biomedical subjects

S Engel

Publications and source records attributed to S Engel.

At least 37 records · Page 2Linked to original sources

Lipoprotein lipase gene polymorphism, cholesterol subfractions and myocardial infarction in large samples of the general population.

OBJECTIVE: Genetic variants of the lipoprotein lipase gene have been associated with dyslipidemia and coronary artery disease. However, data have been inconsistent and are mainly based on selected predominantly male patient groups. METHODS: We evaluated the influence of the HindIII restriction fragment length polymorphism on lipid levels in the general population (1361 participants of a large population-based survey from Augsburg, Germany; 50% women) as well as the association of this polymorphism with the risk of myocardial infarction (MI; genotype frequencies in 1159 patients with documented MI under 60 years of age). RESULTS: In the population-based survey, a highly significant association between the frequent H2H2 genotype and unfavorable cholesterol subfraction levels was observed in men and in postmenopausal women whereas no significant association was observed in premenopausal women (uni- and multivariate analysis). Such unfavorable lipid levels in homozygotes for the H2 allele may be expected to be associated with a 19-25% increased risk to suffer from myocardial infarction (MI). Nevertheless, genotype and allele frequencies in the general population were not different from those in patients with previous MI (H2H2 genotype frequency 51.3% vs. 53.2%, respectively; P=0.63). CONCLUSION: This large study shows that the H2H2 genotype of the lipoprotein lipase gene polymorphism is associated with unfavorable lipid levels. Estrogen status may modulate this association in women. The effects of the genotype on lipid levels were apparently not strong enough to reveal a significant association with MI.

Adult↗

A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo.

We describe a protein with the hallmarks of a chemokine, designated CXCL16, that is made by dendritic cells (DCs) in lymphoid organ T cell zones and by cells in the splenic red pulp. CXCL16 contains a transmembrane domain and both membrane-bound and soluble forms are produced. Naïve CD8 T cells, natural killer T cells and a subset of memory CD4 T cells bind CXCL16, and activated T cells migrated chemotactically to the soluble chemokine. By expression cloning, Bonzo (also known as STRL33 and TYMSTR) was identified as a CXCL16 receptor. CXCL16 may function in promoting interactions between DCs and CD8 T cells and in guiding T cell movements in the splenic red pulp. CXCL16 was also found in the thymic medulla and in some nonlymphoid tissues, indicating roles in thymocyte development and effector T cell trafficking.

Amino Acid Sequence↗

Symptoms, airway responsiveness, and exposure to dust in beech and oak wood workers.

OBJECTIVES: To investigate the relation between levels of cumulative exposure to wood dust and respiratory symptoms and the occurrence of bronchial hyperresponsiveness among beech and oak workers. METHODS: 114 Male woodworkers from five furniture factories and 13 male unexposed controls were examined. The unexposed control group was supplemented by 200 male historical controls. Statistical analyses were performed excluding and including the historical controls. Dust concentration was measured by personal sampling methods. Cumulative exposure to dust was calculated for each woodworker by multiplying the duration of the work by the intensity of exposure (years. mg/m(3)). Bronchial hyperresponsiveness was assessed by the methacholine bronchial challenge test. Subjects were labelled methacholine bronchial challenge positive if forced expiratory volume in 1 second (FEV(1)) fell by >/=20%. The linear dose-response slope was calculated as the last dose divided by the total dose given. RESULTS: 443 Dust samples were collected. The median cumulative exposure to dust was 110 years.mg/m(3) with lower and upper quartiles at 70 and 160 years.mg/m(3) Overall, no declines in FEV(1) and forced vital capacity (FVC) were found with increasing exposures. A dose-response relation was found between intensity of exposure on the one hand, and sore throat, increased prevalence of positive methacholine bronchial challenge tests, and steeper dose-response slope, on the other. CONCLUSION: Exposure to oak and beech dust may lead to the development of sore throat and bronchial hyperresponsiveness.

Adult↗

Evaluation of the aldosterone synthase (CYP11B2) gene polymorphism in patients with myocardial infarction.

Left ventricular remodeling after myocardial infarction involves activation of the renin-angiotensin-aldosterone system. Recently, the biallelic -344T/C polymorphism of the aldosterone synthase gene was associated with increased aldosterone levels, arterial hypertension, diastolic dysfunction, and left ventricular dilatation. We hypothesized that this polymorphism may also affect left ventricular geometry and function after myocardial infarction. By using a standardized questionnaire, as well as anthropometric and echocardiographic measurements, we thus studied 606 patients (533 men and 73 women) who had a myocardial infarction before the age of 60 years. The aldosterone synthase gene polymorphism was analyzed after polymerase chain reaction amplification and restriction enzyme digestion. The results demonstrated that there was no association of the aldosterone synthase gene polymorphism with echocardiographically determined left ventricular dimensions, wall thicknesses, or indexes of systolic or diastolic function. Furthermore, anthropometric data, including blood pressure levels, were balanced between the different genotypes. Finally, the allele frequency was similar for patients with myocardial infarction and a sample group from the normal population (n=1675). The data indicate that the allele status of the aldosterone synthase gene polymorphism is not useful for the identification of patients with myocardial infarction who have impaired left ventricular function or unfavorable remodeling.

Alleles↗

Inhibition of experimental rat glioma growth by decorin gene transfer is associated with decreased microglial infiltration.

Decorin gene therapy for experimental malignant glioma is thought to involve antagonism of immunosuppression induced by glioma-derived transforming growth factor-beta (TGF-beta). TGF-beta is chemotactic for cells of the monocyte macrophage lineage but inhibits their functional activity in many in vitro paradigms. Here, we examined changes in the patterns of microglial infiltration of rat C6 gliomas expressing a decorin transgene. We find that the number of OX42/ED-1-positive microglial cells is reduced rather than enhanced in the presence of decorin. Decorin-expressing gliomas contain lower numbers of MHC class II antigen-expressing microglial cells whereas the relative frequency of MHC I immunoreactivity among microglial cells is increased. Interestingly, the reduction of TGF-beta levels in the tumors by decorin is associated with the de novo expression of inducible nitric oxide synthase (iNOS) in a minority of microglial cells. These data suggest that microglial cells do not participate in the regression of decorin-expressing rat C6 gliomas.

Animals↗

Bax antisense oligonucleotides reduce axotomy-induced retinal ganglion cell death in vivo by reduction of Bax protein expression.

Following transection of the optic nerve (ON), retinal ganglion cells (RGCs) upregulate Bax protein expression and undergo apoptosis. The present study aimed at reducing Bax expression in order to test whether Bax plays a causative role in the induction of secondary RGC apoptosis. Following injection into the vitreous, fluoresceinated oligonucleotides transfected RGCs in vivo at the injection site in the temporal superior retina. Following ON lesion, and repeated injections of a partially phosphorothioated Bax antisense oligonucleotide, but not following injection of control oligonucleotides, expression of Bax protein was locally inhibited, and the number of surviving RGCs was increased in Bax antisense treated rats 8 days after axotomy. Our results indicate that Bax induction is a prerequisite for the execution of RGC apoptosis following ON axotomy. While the Bax antisense strategy offers an exciting perspective to inhibit secondary neuronal degeneration in vivo, both limited transfection efficacy, and the temporal restriction of this effect currently limit the use of this approach with respect to clinical applications for the treatment of neurodegeneration.

Animals↗

Human sperm penetration in different media.

Sperm penetration into bovine cervical mucus and hen egg white using capillary tube penetration was investigated to verify the suitability of the capillary tube penetration test with hen egg white as a test of human sperm function. Semen samples from 50 consecutive patients were used for penetration tests and spermatozoa of a further 10 semen samples were penetrated into bovine cervical mucus and hen egg white for special motility assessment by computer-assisted motility analysis. Penetration tests revealed the well-known different ability of spermatozoa to penetrate into cervical mucus and a different penetration of spermatozoa into egg white for two nearly equal groups (n = 24 and n = 26, respectively). One group showed penetration comparable with cervical mucus and one group a very fast penetration up to the limit of the scale of measurement. Motility assessment of spermatozoa that penetrated into cervical mucus and egg white revealed significant differences in straight-line velocity, linearity and lateral head displacement. The number of spermatozoa selected actively during the penetration procedure was significantly higher in cervical mucus than in hen egg white. Spermatozoa selected by bovine cervical mucus and hen egg white exhibited a different motility pattern. There was significantly better linearity and less lateral head displacement in egg white than in cervical mucus. Sperm penetration into hen egg white appeared to be influenced by different sources of egg white.

Animals↗

[Pleiotropic effects of garlic].

Garlic as a herbal remedy reduces a multitude of risk factors which play a decisive role in the genesis and progression of arteriosclerosis: decrease in total and LDL-cholesterol, increase in HDL-cholesterol, reduction of serum triglyceride and fibrinogen concentration, lowering of arterial blood pressure and promotion of organ perfusion, and, finally, enhancement in fibrinolysis, inhibition of platelet aggregation, and diminution of plasma viscosity. In a prospective, 4-year clinical trial with primary endpoint 'arteriosclerotic plaque volume' it was proven not only a 9 to 18% reduction and 3% regression in plaque volume of the total collective under the influence of standardized garlic powder dragees (900 mg/die LI 111), but also of some facets of the phytopharmacologic pleiotropy of this herb: decrease in LDL level by 4%, increase in HDL concentration by 8%, and lowering in blood pressure by 7%. The reduction of arterial blood pressure is due to an additional opening of K(Ca) ion channels in the membrane of vascular smooth muscle cells that effects its hyperpolarization. This membrane hyperpolarization closes about 20% of the L-type Ca2+ channels, consequence of which is vasodilatation. In human coronary arteries, the increase in vascular diameter by 4% is closely associated with an improvement of coronary perfusion by 18%. These pleiotropic effects of garlic result in a reduction of relative cardiovascular risk for infarction and stroke by more than 50%.

Arteriosclerosis↗

Lipid peroxidation in human spermatozoa and maintenance of progressive sperm motility.

Washed and deep frozen spermatozoa of 46 patients from an infertility clinic were separated into 3 different groups depending on their progressive motility (expressed as the sperm motile efficiency index according to Ishii et al., 1977), determined 0 and 3 h after liquefaction, and were examined for their lipid peroxidation (LPO) potential by means of the thiobarbituric acid assay. Spontaneous and iron-catalysed generation (after 15, 30 and 60 min incubation) of thiobarbituric acid-reactive substances (TBARS) was measured spectrophotometrically. Spontaneous LPO revealed the highest generation of TBARS in the group of spermatozoa with initially normal progressive motility and decreased maintenance of progressive motility after 3 h of aerobic incubation. Iron-catalysed LPO generally revealed the highest amounts of TBARS after 60 min, especially in the aforementioned group with decreased motility maintenance. The differences between this group and the two other groups were highly significant. Consequently, spermatozoa with initially normal progressive motility but decreased maintenance of motility, generated higher amounts of stable LPO products than others, which suggests that loss of motility under aerobic incubation seems to be the consequence of enhanced LPO processes.

Catalysis↗

Severe cervical spinal cord injuries related to rugby union and league football in New South Wales, 1984-1996.

OBJECTIVE: To determine the frequency and circumstances of serious cervical cord injuries associated with rugby union and league football in New South Wales. DESIGN: Retrospective review of patients with rugby football-related cervical spinal cord injuries. SETTING: The two central spinal units in NSW, from January 1984 to July 1996. OUTCOME MEASURES: Admission to spinal units; injury resulting in permanent tetraplegia. RESULTS: During the review period, 115 rugby football players (56 union and 59 league) were admitted to the spinal units because of cervical spinal cord injuries. 49 patients had resultant permanent neurological deficits (complete tetraplegia [quadriplegia])--26 associated with rugby union and 23 with rugby league. Two patients died of injury sequelae within two weeks of admission. There was no significant change in the rate of football-related admissions to spinal units for either code. There was a small decline in the number (from 15 in 1984 to 1987 to 7 in 1992 to 1996) and incidence (from 1.2 to 0.5 per 10,000 participants) of patients with tetraplegia associated with rugby union. When this decline was tested as a trend over the years, it was found to be statistically significant (P = 0.06). No significant trend was found in the tetraplegia data associated with rugby league. Cervical spinal cord injuries leading to complete tetraplegia were most commonly associated with scrum-like plays in union and with tackles in league. CONCLUSION: Serious cervical spinal injuries associated with both codes of rugby continue to occur in NSW. Rugby football in its various forms is still an inherently dangerous game.

Adolescent↗

Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas.

The expression of MUC1 and MUC2 mucin peptide core antigens in gastric carcinomas was studied by immunohistochemistry to determine correlations with TNM stage and histo-pathological classifications as well as a possible prognostic impact. Paraffin-embedded specimens from 128 gastric carcinomas with a minimal follow-up of 5 years were immunostained. In addition to a polyclonal antiserum generated against polymorphic epithelial mucin (MUC1) from human milk, 2 monoclonal antibodies (MAbs), HMFG2 (anti-MUC1) and 4FI (anti-MUC2), were applied. Reactivity of carcinomas was correlated with the classifications of the UICC (TNM), WHO and Laurén. Correlations with overall survival were analyzed using the Kaplan and Meier product limit method. MUC1 immunoreactivity was associated with an advanced pTNM stage. The demonstration of both mucin species (MUC1, MUC2) displayed a statistically significant correlation with tubular/papillary vs. signet-ring cell differentiation as well as with intestinal-type vs. diffuse-type of tumor growth according to Laurén. In particular, MUC2 was only rarely detectable in signet-ring cell and diffuse-type tumors. MUC1 correlated with poor prognosis in all cases and the subgroup of stage I tumors. According to the histopathological classifications, a similar result was observed in signet-ring cell and diffuse-type carcinomas. In contrast, MUC2 reactivity was associated with a favourable prognosis of intestinal-type carcinomas. In the non-neoplastic gastric mucosa, both peptide cores were recognized in the superficial epithelium, whereas parietal cells contained only MUC1, and intestinal metaplasia almost exclusively MUC2 antigens. We conclude that the mucin peptide core antigens are suitable markers for the tubule-rich gastric carcinomas, which may in part be derived from intestinal metaplasia. In addition, MUC1 may exert a prognostic relevance and appears to be involved in the progression of diffuse-type tumors.

Adult↗

Energy expenditure during gait using the walkabout and isocentric reciprocal gait orthoses in persons with paraplegia.

OBJECTIVE: To compare the energy expenditure during walking using the Walkabout Orthosis (WO) and the Isocentric Reciprocal Gait Orthosis (IRGO) in persons with paraplegia. DESIGN: A randomized cross-over design. PATIENTS: Ten individuals with complete T9-12 paraplegia. INTERVENTIONS: Subjects were trained to walk using the WO and the IRGO with elbow crutches. MAIN OUTCOME MEASURES: Subjects' energy expenditures during walking using each orthosis over three different terrains--flat tile, flat carpet, and 4 degrees uphill ramp--were compared. Data collected included expired ventilation (L/min), heart rate (beats/ min), speed of walking (m/min), oxygen uptake (VO2; L/min and mL/kg/min), oxygen cost (O2 cost; mL/kg/m), and Physical Cost Index (PCI; beats/m). Subjects walked at a self-selected pace. RESULTS: Subjects walked significantly slower with the WO than with the IRGO, regardless of the surface (p < .05). The average speed of walking ranged from 5.2+/-1.3 for the WO on the tiled surface to 11.5+/-2.3m/min for the IRGO on the carpeted surface. Despite marked differences in self-selected walking speeds between the two orthoses, there were no differences in either heart rate or VO2 among orthoses or surfaces. However, the O2 cost of gait was significantly greater for the WO (range, 3.95 to 4.91mL/kg/m) compared with the IRGO (range, 1.6 to 1.8mL/kg/m). Likewise, the PCI was significantly greater using the WO (range, 8.4 to 10.3beats/m) than the IRGO (range, 4.3 to 7.0beats/m). CONCLUSIONS: This study shows that the metabolic demands of walking with the WO are greater than walking with the IRGO in individuals with T9-12 paraplegia.

Adult↗

Investigations on the detection of Chlamydia trachomatis infections in infertile male outpatients.

The determination of Chlamydia antibodies in serum is unsuitable for diagnosing infertility in men. The determination of secretory IgA in seminal plasma would seem to be of greater relevance. Since antibodies against C. trachomatis and C. pneumoniae can be detected, a species-specific test for the diagnosis of infections of the male genital tract should be used. Only at relatively high titers (> or = 1:400) do genus-specific tests agree with the species-specific micro-immunofluorescence test. Whether such values can be taken as a true indicator of a local, chronic infection remains to be investigated.

Adult↗

Histopathological subtypes and prognosis of gastric cancer are correlated with the expression of mucin-associated sialylated antigens: Sialosyl-Lewis(a), Sialosyl-Lewis(x) and sialosyl-Tn.

The expression of three sialylated mucin-associated antigens - sialosyl-Lewisa (SLEA), sialosyl-Lewisx (SLEX) and sialosyl-Tn (STN) - and their correlation with the TNM stage, histopathological growth pattern and prognosis was investigated in a series of 127 gastric carcinomas. Various classification systems (pTNM, WHO and Laurén) did not display any correlation with an expression of the sialomucin antigens under study. SLEA reactivity was strongly associated with an unfavorable outcome of the total population, whereas SLEX and STN did not exert such an impact. However, in the subgroups of pTNM stage I as well as pN0 patients, SLEA and SLEX reactivity of the tumors was associated with a worse prognosis. In the subgroup of diffuse-type cancers as defined according to Laurén's classification, the expression of all three antigens indicated a worsening of the prognosis.

Adult↗

Colour tuning in human visual cortex measured with functional magnetic resonance imaging.

The primate retina contains three classes of cones, the L, M and S cones, which respond preferentially to long-, middle- and short-wavelength visible light, respectively. Colour appearance results from neural processing of these cone signals within the retina and the brain. Perceptual experiments have identified three types of neural pathways that represent colour: a red-green pathway that signals differences between L- and M-cone responses; a blue-yellow pathway that signals differences between S-cone responses and a sum of L- and M-cone responses; and a luminance pathway that signals a sum of L- and M-cone responses. It might be expected that there are neurons in the primary visual cortex with response properties that resemble these three perceptual pathways, but attempts to find them have led to inconsistent results. We have therefore used functional magnetic resonance imaging (fMRI) to examine responses in the human brain to a large number of colours. In visual cortical areas V1 and V2, the strongest response is to red-green stimuli, and much of this activity is from neurons receiving opposing inputs from L and M cones. A strong response is also seen with blue-yellow stimuli, and this response declines rapidly as the temporal frequency of the stimulus is increased. These responses resemble psychophysical measurements, suggesting that colour signals relevant for perception are encoded in a large population of neurons in areas V1 and V2.

Brain Mapping↗

hsp47 and hsp70 gene expression is differentially regulated in a stress- and tissue-specific manner in zebrafish embryos.

We have examined differences in the spatial and temporal regulation of stress-induced hsp47 and hsp70 gene expression following exposure of zebrafish embryos to heat shock or ethanol. Using Northern blot analysis, we found that levels of hsp47 and hsp70 mRNA were dramatically elevated during heat shock in 2-day-old embryos. In contrast, ethanol exposure resulted in strong upregulation of the hsp47 gene whereas hsp70 mRNA levels increased only slightly following the same treatment. Whole-mount in situ hybridization analysis revealed that hsp47 mRNA was expressed predominantly in precartilagenous cells, as well as several other connective tissue cell populations within the embryo following exposure to either stress. hsp70 mRNA displayed a very different cell-specific distribution. For example, neither stress induced hsp70 mRNA accumulation in precartilagenous cells. However, high levels of hsp70 mRNA were detectable in epithelial cells of the developing epidermis following exposure to heat shock, but not to ethanol. These cells did not express the hsp47 gene following exposure to either of these stresses. The results suggest the presence of different inducible regulatory mechanisms for these genes which operate in a cell- and stress-specific manner in zebrafish embryos.

Amino Acid Sequence↗

Functional outcomes attained by T9-12 paraplegic patients with the walkabout and the isocentric reciprocal gait orthoses.

OBJECTIVE: To compare the functional outcomes attained by persons with paraplegia using the Walkabout Orthosis (WO) and the Isocentric Reciprocal Gait Orthosis (IRGO). DESIGN: A randomized crossover design. PATIENTS: Ten subjects with complete lesions between T9-T12. INTERVENTIONS: Over two 8-week periods, subjects were taught to use each orthosis in conjunction with elbow crutches. MAIN OUTCOME MEASURES: After each 8-week training period, subjects were assessed on their ability to perform five different sets of key skills associated with functional ambulation. RESULTS: There were no differences between orthoses in the ability of subjects to don and doff the orthoses, get up and down stairs and curbs, or walk on a flat surface. Subjects required significantly more assistance when using the WO to walk over inclined surfaces (median IRGO = "independent," median WO = "minimal assistance"; p = .03) but less assistance when using the WO to get from sitting to standing and standing to sitting (median IRGO = "moderate assistance," median WO = "minimal assistance"; p = .03). In addition, subjects walked significantly faster with the IRGO both on the flat (mean IRGO = .34 m/sec +/- .18, mean WO = .14 m/sec +/- .12; p = .002) and on inclined surfaces. CONCLUSIONS: Although it is easier to stand up and sit down with the WO, the IRGO facilitated a faster and more independent gait. Neither orthosis enabled subjects to be fully independent in the key skills necessary for functional ambulation after 8 weeks of training.

Activities of Daily Living↗