Biomedical subjects

A Wagner

Publications and source records attributed to A Wagner.

At least 145 records · Page 8Linked to original sources

PubMed2001

The yeast protein interaction network evolves rapidly and contains few redundant duplicate genes.

In this paper, the structure and evolution of the protein interaction network of the yeast Saccharomyces cerevisiae is analyzed. The network is viewed as a graph whose nodes correspond to proteins. Two proteins are connected by an edge if they interact. The network resembles a random graph in that it consists of many small subnets (groups of proteins that interact with each other but do not interact with any other protein) and one large connected subnet comprising more than half of all interacting proteins. The number of interactions per protein appears to follow a power law distribution. Within approximately 200 Myr after a duplication, the products of duplicate genes become almost equally likely to (1) have common protein interaction partners and (2) be part of the same subnetwork as two proteins chosen at random from within the network. This indicates that the persistence of redundant interaction partners is the exception rather than the rule. After gene duplication, the likelihood that an interaction gets lost exceeds 2.2 x 10(-3)/Myr. New interactions are estimated to evolve at a rate that is approximately three orders of magnitude smaller. Every 300 Myr, as many as half of all interactions may be replaced by new interactions.

Evolution, Molecular↗

PubMed2001

Placement of endosteal implants in the zygoma after maxillectomy: a Cadaver study using surgical navigation.

Endosteal implants facilitate obturator prosthesis fixation in tumor patients after maxillectomy. Previous clinical studies have shown, however, that the survival of implants placed into available bone after maxillectomy is generally poor. Nevertheless, implants positioned optimally in residual zygomatic bone provide superior stability from a biomechanical point of view. In a pilot study, the authors assessed the precision of VISIT, a computer-aided surgical navigation system dedicated to the placement of endosteal implants in the maxillofacial area. Five cadaver specimens underwent hemimaxillectomy. The cadaver head was matched to a preoperative high-resolution computed tomograph by using implanted surgical microscrews as fiducial markers. The position of a surgical drill relative to the cadaver head was determined with an optical tracking system. Implants were placed into the zygomatic arch, where maximum bone volume was available. The results were assessed using tests for localization accuracy and postoperative computed tomographic scans of the cadaver specimens. The localization accuracy of landmarks on the bony skull was 0.6 +/- 0.3 mm (average +/- SD), as determined with a 5-df pointer probe; the localization accuracy of the tip of the implant burr was 1.7 +/- 0.4 mm. The accuracy of the implant position compared with the planned position was 1.3 +/- 0.8 mm for the external perforation of the zygoma and 1.7 +/-1.3 mm for the internal perforation. Eight of 10 implants were inserted with maximal contact to surrounding bone, and two implants were located unfavorably. Reliable placement of implants in this region is difficult to achieve. The technique described in this article may be very helpful in the management of patients after maxillary resection with poor support for obturator prostheses.

Cadaver↗

PubMed2001

Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree.

Hereditary non-polyposis colorectal cancer (HNPCC) is the most common genetic susceptibility syndrome for colorectal cancer. HNPCC is most frequently caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2 and MLH1. Recently, mutations in another MMR gene, MSH6 (also known as GTBP), have also been shown to result in HNPCC. Preliminary data indicate that the phenotype related to MSH6 mutations may differ from the classical HNPCC caused by defects in MSH2 and MLH1. Here, we describe an extended Dutch HNPCC family not fulfilling the Amsterdam criteria II and resulting from a MSH6 mutation. Overall, the penetrance of colorectal cancer appears to be significantly decreased (p<0.001) among the MSH6 mutation carriers in this family when compared with MSH2 and MLH1 carriers (32% by the age of 80 v >80%). Endometrial cancer is a frequent manifestation among female carriers (six out of 13 malignant tumours). Transitional cell carcinoma of the urinary tract is also relatively common in both male and female carriers (10% of the carriers). Moreover, the mean age of onset of both colorectal cancer (MSH6 v MSH2/MLH1 = 55 years v 44/41 years) and endometrial carcinomas (MSH6 v MSH2/MLH1 = 55 years v 49/48 years) is delayed. As previously reported, we confirm that the pattern of microsatellite instability, in combination with immunohistochemical analysis, can predict the presence of a MSH6 germline defect. The detailed characterisation of the clinical phenotype of this kindred contributes to the establishment of genotype-phenotype correlations in HNPCC owing to mutations in specific mismatch repair genes.

Adult↗

PubMed2001

Benzodiazepine receptor quantification in Huntington's disease with [(123)I]omazenil and SPECT.

OBJECTIVES: Increasing evidence suggests that metabolic changes predate neuronal death in Huntington's disease and emission tomography methods (PET and SPECT) have shown changes in glucose consumption and receptor function in early and possibly even presymptomatic disease. Because the GABA(A)-benzodiazepine receptor complex (BZR) is expressed on virtually all cerebral neurons BZR density images may be used to detect neuronal death. In this study the regional cerebral [(123)I]iomazenil binding to BZR was determined in patients with Huntington's disease and normal controls by a steady state method and SPECT. METHODS: Seven patients mildly to moderately affected by Huntington's disease and seven age matched controls were studied. Brain CT was performed on all subjects. In each subject two [(123)I]iomazenil-SPECT measurements were acquired-one with and one without infusion of flumazenil. The affinity constant of flumazenil (Kd) was calculated from the paired distribution volumes (DV) and the free plasma flumazenil concentration. The distribution volume of [(123)I]iomazenil in the unblocked condition (DV(0)) reflects the ratio between BZR density and Kd. RESULTS: Flumazenil Kd was similar in the Huntington's disease group and the control group (11.3 v 11.2 mM). For the Huntington's disease group a 31% reduction in striatal DV(0) (p=0.03) was found. In the cortical regions, DV(0) was similar in patients and in controls. In Huntington's disease, DV(0) correlated significantly with functional capacity (p=0.04) and chorea symptoms (p=0.02). The clinically least affected patients displayed DV(0)s within the range of those of the control group (19-35 ml/ml). CONCLUSIONS: The finding of an unchanged Kd of flumazenil in patients indicates that the BZR is functionally intact in Huntington's disease. That is, the reduction in DV(0) for BZR represents a selective decrease in the number of striatal BZRs. DV(0) significantly correlated with functional loss and [(123)I]iomazenil-SPECT could be an important tool for validation of the effect of future therapeutic strategies aimed at limiting oxidative stress and free radicals in Huntington's disease.

Adult↗

PubMed2001

Pilot study on liposomal recombinant human superoxide dismutase for the treatment of Peyronie's disease.

OBJECTIVE: To assess the efficacy and safety of liposomally encapsulated recombinant human superoxide dismutase (lrhSOD) for the treatment of Peyronie's disease. METHODS: In an uncontrolled phase-2 study, 20 patients with Peyronie's disease were treated with a gel containing lrhSOD (1.5 mg/g). Patients with penile deviation of >45 degrees or plaque calcifications of >5 mm were regarded as candidates for surgical correction and excluded from this study. RESULTS: Elimination of pain was observed in 7/13 patients (in 2 patients after only 3 days of therapy), and an almost complete resolution of pain was reported by the remaining 6/13 patients. Plaque size was reduced in 8/14 patients. Minimal improvement of penile deviation was observed in 3/12 patients. Post-therapeutic improvement of sexual function, mainly due to cessation of pain, was reported by 12/15 patients. No systemic or local side effects were observed. CONCLUSION: In the present study, 100% pain relief as well as a plaque size reduction in 56% of Peyronie's disease patients were observed after a maximum of 6 weeks of lrhSOD therapy. The convenience and safety of lrhSOD gel therapy were superior compared to other current regimens. The present results suggest that lrhSOD gel is a promising treatment for patients with early stage Peyronie's disease. Early institution of lrhSOD therapy may prevent disease progression to penile deviation. The present preliminary results are the basis of a placebo-controlled randomized study.

Adult↗

PubMed2001

Identification of TIA-1+ and granzyme B+ cytotoxic T cells in lichen sclerosus et atrophicus.

BACKGROUND: The onset and persistence of cutaneous lichen sclerosus et atrophicus (LSA) are linked to the presence of an inflammatory infiltrate of CD3+ T cells that includes CD4+ and CD8+ cells. The functional relevance of the presence of these cells is unknown. OBJECTIVE: The study intended to quantify resting and activated cytotoxic T cells in LSA lesions. METHODS: Twenty patients with active LSA were studied. Skin-infiltrating T cells were immunohistologically characterized with antibodies against CD3, CD8, T-cell-restricted intracellular antigen (TIA-1) and granzyme B (GrB). TIA-1 labels cytotoxic granules of resting and activated T cells, whereas GrB designates activated cytotoxic T lymphocytes (CTL). RESULTS: In all cases, numerous T cells were consistently found expressing cytotoxic granules. The results indicated a high number of infiltrating CD8+ TIA+ T cells. Furthermore, a notable number of GrB+ activated CTL associated with hydropic degeneration of the basal cell layer were found within the dermal infiltrate and at the dermoepidermal interface. CONCLUSION: This study shows that a high proportion of skin-infiltrating T cells in LSA has a potential cytotoxic function. The results indicate that hydropic degeneration of basal keratinocytes may at least partially be mediated by CTL-dependent mechanisms. Our data also indicate that a cell-mediated immune response may play an important role in the pathogenesis of the disease.

Adult↗

PubMed2001

Producer satisfaction, efficiency, and investment cost factors of different milking systems.

A modernization survey was used to determine producer satisfaction, efficiency, and investment cost measures of different milking systems. The 301 producers included in this study expanded herd size by at least 50% for smaller herds (60 to 100 cows), or 40% for larger herds, (>100 cows) between 1994 and 1998. The milking systems analyzed and compared were stall barn with pipeline, flat barn parlor walk through and back-out, and herringbone or parallel parlor in old barn or new building. Investment costs per cow were higher for pit parlor in new building, $979. Parallel parlors had a higher cost per milking unit, $13,201, and cost per cow, $860, than herringbone, $8944 and $582, respectively. Herringbone parlors were used more hours per day, 10.75, than parallel parlors, 8.84, of similar size. Pit parlors in new buildings were more labor efficient, as measured by cows per worker hour, than stall barns with pipeline or flat parlor or pit parlors in old barns. Herringbone and parallel parlor in new building were similar for cows per hour (82 and 83) and cows per worker hour (41 and 43). Parallel or herringbone parlors in old barns had fewer cows per hour (63 and 58) than parallel or herringbone parlors in new buildings. Survey respondents showed greater satisfaction for time spent milking, physical comfort of milker, and milk quality for parlor types over stall barn with pipeline. Safety of operator satisfaction was higher for pit parlors than flat parlors or stall barn. No difference in satisfaction was observed between parallel and herringbone parlors.

Animals↗

PubMed2001

Spiral computed tomographic imaging related to computerized ultrasonographic images of carotid plaque morphology and histology.

OBJECTIVE: Echolucency of carotid atherosclerotic plaques, as evaluated by computerized B-mode ultrasonographic images, has been associated with an increased incidence of brain infarcts on cerebral computed tomographic scans. We tested the hypotheses that characterization of carotid plaques on spiral computed tomographic images correlates with that on computerized B-mode ultrasonographic images and that spiral computed tomographic imaging predicts the histomorphometric plaque content. METHODS: The study included 38 patients with neurologic symptoms and at least 50% stenosis of the ipsilateral carotid artery. High-resolution B-mode ultrasonographic images and spiral computed tomographic images of carotid plaques were computer processed to yield a quantitative measure, the gray scale level of the plaque. RESULTS: The mean Hounsfield value for spiral computed tomographic images correlated with the gray scale median for B-mode ultrasonographic images (univariate linear regression analysis: r = 0.45; P = .01) and the histologic content of calcification in the plaque (r = 0.34; P = .04) but not with lipid, hemorrhage, or fibrous tissue in the plaque. CONCLUSIONS: Spiral computed tomographic imaging seems to correlate with B-mode ultrasonographic imaging for showing plaque characteristics. Spiral computed tomographic attenuation was also correlated with the amount of calcification noted on histologic examination but not with lipid and hemorrhage, the components thought to characterize vulnerable, rupture-prone plaques.

Carotid Arteries↗

PubMed2001

Obstetric dislocation of the thoracic spine: case report and review of the literature.

A fracture dislocation of the upper thoracic spine with spinal cord injury is reported in a neonate. This rare injury is associated with attendant predisposing obstetric circumstances (breech transverse presentations, large baby size) that can alert clinicians of potential problems and aid in the diagnosis of neonatal hypotonia and paralysis.

Birth Injuries↗

PubMed2001

Sinusitis and ischemic stroke.

Acute sinusitis is a prevalent and generally uncomplicated infection that is normally resolved by medical therapy. However, severe neurological complications are known, and comprise of cerebral abscess, cavernous sinus thrombosis, meningitis, and epidural or subdural empyema. We report a case about a 10-year-old girl with a severe acute pansinusitis and ischemic stroke in the right lentiform nucleus and the anterior part of the right internal capsule. Possible explanations for this rare combination are discussed.

Acute Disease↗

PubMed2000

An original traceless linker strategy for solid-phase synthesis of N,N',N''-substituted guanidines.

An original sequence for solution- and solid-phase synthesis of N,N',N"-trisubstituted guanidines is described. The sequence involves as key intermediate a bis-electrophilic chlorothioformamidine that is stable, easy to prepare and also easy to handle. Supported chlorothioformamidine, prepared in two steps from Merrifield resin, undergoes smooth nucleophilic addition of a primary amine to afford the corresponding supported isothiourea. The guanidine is obtained in satisfactory yield and good purity through a functionalizing-release process by heating the supported isothiourea in the presence of a primary amine in toluene at 100 degrees C. Compatibility of this sequence with several functional groups is demonstrated.

Chromatography, High Pressure Liquid↗

PubMed2000

[Ischemic cerebral apoplexy in children].

During two years we identified eight children aged 1.5-10 years with cerebral ischaemic stroke. Prior to the stroke seven of eight children were in full health. Predisposing factors were endocarditis and trauma. Four children had prodomal symptoms prior to the infarction. All had acute hemiparesis on admission. Three of the children had fever, and five had varicellazoster infection three to 18 months prior to the stroke. Three children had convulsions. Seven of eight children had stenoses or occlusions of the middle cerebral or the basilar artery. Five children have persistent deficits and none have died. The children did not have coagulopathies, hypertension or arteriosclerosis. Echocardiography did not show patent foramen ovale. Early clinical and neuroradiological investigations are of importance in reaching the appropriate diagnosis.

Cerebral Hemorrhage↗

PubMed2000

Deconditioning in patients with chronic low back pain: fact or fiction?

STUDY DESIGN: Prospective case series with historical controls (normative data). OBJECTIVES: To compare aerobic fitness levels in patients with chronic low back pain with those published on a sample of 295 healthy subjects. SUMMARY OF BACKGROUND DATA: Clinical belief holds that patients with chronic low back pain have low fitness levels as a result of inactivity because of pain. Because few studies have investigated the level of aerobic fitness in these patients, however, it remains unclear how fitness levels in patients with chronic low back pain patients compare with those published a sample of the normative population. METHODS: A sample of 50 patients with chronic low back pain with a mean pain duration of 40 months referred to an outpatient pain clinic performed a symptom-limited modified treadmill test. Aerobic fitness levels were determined by indirect calorimetry to measure oxygen consumption (VO2). Predicted maximum oxygen consumption (VO2max) levels were calculated for all subjects. Multiple regression analysis with adjustment for age and sex yielded prediction equations for men and women separately. Ninety-five percent confidence intervals were calculated for predicted mean oxygen consumption (VO2) and the slope of the equations. These were compared to established prediction equations on healthy subjects. RESULTS: Prediction equations for estimated maximum oxygen consumption (VO2max) in patients with chronic low back pain equal those in healthy sedentary men and active women. CONCLUSIONS: Levels of aerobic fitness in patients with chronic low back pain are comparable with those in healthy subjects.

Adult↗

PubMed2000

L-Tryptophan does not influence acute ventilatory response at moderate altitude.

Altitude induced insomnia is a very common symptom in mountaineering. Conventional hypnotics such as benzodiazepines potentially can be associated with untoward side effects because they can impair ventilatory adaptation to hypoxia at altitude. The objective of our study was to evaluate the effect of a alternative potentially sedative drug, L-tryptophan on ventilation at moderate altitude. STUDY DESIGN, METHODS AND RELEVANT RESULTS: Randomised, double blind, placebo controlled crossover trial. Blood gas analysis of 8 healthy subjects was performed before and one hour after oral administration of 500 mg L-tryptophan or placebo at altitudes of 171 m and at 3,000 m. PaO2 and PaCO2 before and after L-Tryptophan or placebo medication did not change significantly at neither level of altitude investigated. CONCLUSION: L-tryptophan does not impair ventilatory adaptation to mild hypoxia at moderate altitude.

Adaptation, Physiological↗

PubMed2000

Isospin fractionation in nuclear multifragmentation

Isotopic distributions for light particles and intermediate mass fragments have been measured for 112Sn+112Sn, 112Sn+124Sn, 124Sn+112Sn, and 124Sn+124Sn collisions at E/A = 50 MeV. Isotope, isotone, and isobar yield ratios are utilized to estimate the isotopic composition of the gas phase at freeze-out. Analyses within the equilibrium limit imply that the gas phase is enriched in neutrons relative to the liquid phase represented by bound nuclei. These observations suggest that neutron diffusion is commensurate with or more rapid than fragment production.

Journal Article↗

PubMed2000

Direct evidence for the breakdown of the N = 8 shell closure in 12Be

Partial cross sections and corresponding momentum distributions have been studied in the one-neutron knockout reaction ( 12Be,11Be+gamma) on a 9Be target at 78 MeV/nucleon. The resulting spectroscopic factors for the only two bound states of 11Be are 0.42+/-0.06 ( 1/2(+)) and 0.37+/-0.06 ( 1/2(-)), where the errors are experimental only. This result shows that N = 8 is not a good closed shell in the neutron-rich 12Be and that the last neutron pair is two-thirds in the ( 1s(2)+0d(2)) intruder configuration.

Journal Article↗

PubMed2000

Emission pattern of high-energy pions: A new probe for the early phase of heavy-Ion collisions

The emission pattern of charged pions has been measured in Au+Au collisions at 1 GeV/nucleon incident energy. In peripheral collisions and at target rapidities, high-energy pions are emitted preferentially towards the target spectator matter. In contrast, low-energy pions are emitted predominantly in the opposite direction. The corresponding azimuthal anisotropy is explained by the interaction of pions with projectile and target spectator matter. This interaction with the spectator matter causes an effective shadowing which varies with time during the reaction. Our observations show that high-energy pions stem from the early stage of the collision whereas low-energy pions freeze out later.

Journal Article↗

PubMed2000

Aerobic fitness testing in patients with chronic low back pain: which test is best?

STUDY DESIGN: This is a randomized comparison of three exercise tests in a sample of 30 patients with chronic low back pain. OBJECTIVES: To determine, by comparing three exercise tests, which test yields the highest peak and predicted oxygen consumption in a sample of patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: Little is known about the level of aerobic fitness in patients with chronic low back pain, although many rehabilitation programs emphasize aerobic exercise as an important part of their therapy. Measurement of aerobic fitness levels in these patients remains a problem. In healthy individuals, the highest oxygen consumption values come from exercise tests that use the largest muscle groups. For a number of reasons, this may not be true in patients with chronic low back pain. METHODS: In this study, 30 participants with chronic low back pain performed three symptom-limited maximal exercise tests: a treadmill, an upper extremity ergometer, and a bicycle ergometer. The tests were administered in randomized order. Heart rate was continuously monitored and oxygen consumption in terms of mL/kg/minute was measured by indirect calorimetry each 30 seconds. RESULTS: The statistical difference among the tests was highly significant (P < 0.0001). The treadmill test yielded the highest peak and predicted oxygen consumption followed by the bicycle and the upper extremity ergometer test, respectively. CONCLUSIONS: The treadmill test is the best test for measuring aerobic fitness levels in patients with chronic low back pain. It yielded the highest peak oxygen consumption compared with the other tests, coming closest to measuring maximal oxygen consumption.

Adolescent↗