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PubMed2001

Stroke genomics: approaches to identify, validate, and understand ischemic stroke gene expression.

Sequencing of the human genome is nearing completion and biologists, molecular biologists, and bioinformatics specialists have teamed up to develop global genomic technologies to help decipher the complex nature of pathophysiologic gene function. This review will focus on differential gene expression in ischemic stroke. It will discuss inheritance in the broader stroke population, how experimental models of spontaneous stroke might be applied to humans to identify chromosomal loci of increased risk and ischemic sensitivity, and also how the gene expression induced by stroke is related to the poststroke processes of brain injury, repair, and recovery. In addition, we discuss and summarise the literature of experimental stroke genomics and compare several approaches of differential gene expression analyzes. These include a comparison of representational difference analysis we have provided using an experimental stroke model that is representative of stroke evolution observed most often in man, and a summary of available data on stroke differential gene expression. Issues regarding validation of potential genes as stroke targets, the verification of message translation to protein products, the relevance of the expression of neuroprotective and neurodestructive genes and their specific timings, and the emerging problems of handling novel genes that may be discovered during differential gene expression analyses will also be addressed.

Animals↗
PubMedDate not supplied

Three-dimensional verification of patient placement during radiotherapy using portal images.

The use of a single portal image for the three-dimensional verification of patient placement during radiotherapy has been investigated. In this study, a deviation in the patient positioning is quantified by a three-dimensional translation and rotation of the patient. The parameter values are obtained by fitting the projections of anatomical match points in the simulator and the portal image, using the three-dimensional gantry coordinates of these points in the intended treatment setup. Two methods for finding an analytical solution for the fitting problem are presented. One method yields a solution from the affine transformation of the portal image (shift, rotation, magnification, and stretching in a specified direction) that fits the projections of the match points on the simulator image. The second and more accurate method yields a solution that expresses the estimated parameter values and their covariances as functions of image and three-dimensional gantry coordinates of the selected matchpoints. The robustness and sensitivity of the solution is implicitly given by these expressions. The applications of these methods are illustrated by experiments with a human pelvic bone.

Humans↗
PubMed1999

Vestibular autorotation test in primary selection of military student pilots using neural networks.

BACKGROUND: Selection of student pilots to the Royal Danish Air Force involves a physical examination including a vestibular test. Usually tests for selection proposes are not well documented. HYPOTHESIS: The result of the vestibular autorotation test (VAT) is correlated to the ability to learn to fly in a military context. METHODS: A Multi Layer Perception neural network with three layers configured as a Back Propagation Network was tested using data originating from horizontal VAT of 59 student pilot candidates, given the outcome of the pre-jet basic flight check. In the analysis the leave-one-out method was used. RESULTS: Based on horizontal data only the network correctly classified the student pilot candidates as having been passed or rejected within a verification error margin < 0.1. CONCLUSION: The result indicates that VAT performed at the initial physical examination is a powerful tool for the elimination of unfit student pilot candidates when data are analyzed in neural networks.

Adolescent↗
PubMed1990

[Value of endomyocardial biopsy in the assessment of the degree of the changes in myocarditis].

Right ventricular diagnostic biopsy was performed in 25 patients (12 females and 13 males) aged 19-48 (mean 32) with suspicion of acute or subacute myocarditis for definitive diagnosis verification and to determine indications for therapy with corticosteroids or azathioprine. 3-4 specimens taken from different sites of ventricle were estimated under the light microscope according to Dallas classification distinguishing active myocarditis with or without fibrosis from borderline myocarditis with inflammatory infiltration not causing myocytes damage. Routine clinical and laboratory tests, echocardiographic examination, ECG Holter monitoring and nuclear examination to evaluate left ventricular ejection fraction were performed in all patients. 6 patients underwent coronarography to exclude atherosclerotic changes in coronary arteries. Bioptic examination result confirmed myocarditis suspicion in all patients. Active inflammation was stated in 18 patients including 7 with coexisting fibrosis. Borderline myocarditis was stated in 7 cases. Comparison of clinical examination results with those of pathomorphologic study made possible to state, that tachycardia, cardiac murmur, arrhythmias and left ventricular function impairment were frequent observed in the group of active myocarditis. Ejection fraction less than 30% was observed only in patients with active myocarditis and mainly in those with coexisting fibrosis. Based on performed study we consider that myocardial biopsy allows not only to diagnose myocarditis but also is helpful for lesion extent assessment in myocardium with all clinical implications.

Acute Disease↗
PubMed1989

[Method and initial results of percutaneous ultrasound-controlled sclerotherapy of parathyroid adenoma in secondary or tertiary hyperparathyroidism].

In 16 of 96 patients with clinical, roentgenological and biochemical signs of hyperparathyroidism due to chronic renal failure the parathyroid adenomas were detected ultrasonographically. Verification of the adenoma was done using fine-needle biopsy and cytological evaluation. In 8 patients an ultrasonographic-guided sclerotherapy using absolute ethanole was performed. The efficacy of this method was evaluated by control of the biochemical parameters. In all cases a reduction of the serum calcium level and of the parathormone was observed. This method may represent an adjuvant therapy in the treatment of renal hyperparathyroidism.

Adenoma↗
PubMed1983

31P NMR spectroscopy of brain and heart.

31P NMR technique was applied to monitor changes in the energy metabolism of the brain and heart of unanesthetized cats during shock, stroke, hypoxia and increased functional activity. The results show that in these tissues content of inorganic phosphate, sugar phosphates, phosphocreatine and of ATP can be measured decently in awake animals. At the same time this technique has the great advantage over the disruptive biochemical methods that it gives a semi-continuous reading and it is non-invasive. Our findings are summarized as follows: Hemorrhagic shock resulted in an irreversible deterioration of the energy state of the brain. Our stroke model led to a very marked increase in Pi and a decrease CP in the brain but these changes were reversible. The ATP levels of the brain as it was indicated by 31p NMR spectra were not affected by hemorrhagic shock and stroke which can be attributed probably by the reduced rate of ATP consumption. The verification of this hypothesis needs further work. During increased mechanical performance the levels of SP, and Pi increased, ATP decreased, while CP was not influenced in the heart.

Animals↗
PubMed2005

Characterization of human cytomegalovirus glycoprotein-induced cell-cell fusion.

Human cytomegalovirus (CMV) infection is dependent on the functions of structural glycoproteins at multiple stages of the viral life cycle. These proteins mediate the initial attachment and fusion events that occur between the viral envelope and a host cell membrane, as well as virion-independent cell-cell spread of the infection. Here we have utilized a cell-based fusion assay to identify the fusogenic glycoproteins of CMV. To deliver the glycoprotein genes to various cell lines, we constructed recombinant retroviruses encoding gB, gH, gL, and gO. Cells expressing individual CMV glycoproteins did not form multinucleated syncytia. Conversely, cells expressing gH/gL showed pronounced syncytium formation, although expression of gH or gL alone had no effect. Anti-gH neutralizing antibodies prevented syncytium formation. Coexpression of gB and/or gO with gH/gL did not yield detectably increased numbers of syncytia. For verification, these results were recapitulated in several cell lines. Additionally, we found that fusion was cell line dependent, as nonimmortalized fibroblast strains did not fuse under any conditions. Thus, the CMV gH/gL complex has inherent fusogenic activity that can be measured in certain cell lines; however, fusion in fibroblast strains may involve a more complex mechanism involving additional viral and/or cellular factors.

Animals↗
PubMed1998

Physical and temporal scaling considerations in a robot model of cricket calling song preference.

Behavioral experiments with crickets show that female crickets respond to male calling songs with syllable rates within a certain bandwidth only. We have made a robot model in which we implement a simple neural controller that is less complex than the controllers traditionally hypothesized for cricket phonotaxis and syllable rate preference. The simple controller, which had been successfully used with a slowed and simplified signal, is here demonstrated to function, using songs with identical parameters to those found in real male cricket song, using an analog electronic model of the peripheral auditory morphology of the female cricket as the sensor. We put the robot under the same experimental conditions as the female crickets, and it responds with phonotaxis to calling songs of real male Gryllus bimaculatus. Further, the robot only responds to songs with syllable rates within a bandwidth similar to the bandwidth found for crickets. By making polar plots of the heading direction of the robot, we obtain behavioral data that can be used in statistical analyses. These analyses show that there are statistically significant differences between the behavioral responses to calling songs with syllable rates within the bandwidth and calling songs with syllable rates outside the bandwidth. This gives the verification that the simple neural control mechanism (together with morphological auditory matched filtering) can account for the syllable rate preference found in female crickets. With our robot system, we can now systematically explore the mechanisms controlling recognition and choice behavior in the female cricket by experimental replication.

Animals↗
PubMed2000

[Hepatocyte proliferation and DNA content in chronic hepatitis C].

Apart from inflammatory reaction, the death of hepatocytes is also a characteristic of chronic hepatitis. Necroinflammation is followed by compensatory proliferation, which plays a rather important role in maintaining the liver function. Authors studied the DNA content of hepatocytes in patients with chronic hepatitis C, and determined the ratio of hepatocytes in phases G1, S and G2 to determine the hepatocyte proliferation and regeneration capacity of the liver. Liver biopsy samples were taken from 23 patients with chronic hepatitis C and from 16 with chronic hepatitis with non viral origin, from which nuclear suspension counts were done based on the histological slides. A total of 16 normal liver tissue samples served as control. The DNA index, G1, S, G2 and polyploid fraction were determined using the DNACE (Digital Image Analyzer for Nuclear Deoxyribonucleic Acid Content Estimation, KFKI/NIO, Hungary) digital imaging process. The DNA index was found to be significantly higher in the chronic hepatitis C than in the non-C group, with the verification of aneuploidy (DI > 1.10). The chronic non-C hepatitis cases showed lower G1 (88 +/- 6) and higher S (7.8 +/- 6.6) fractions. In comparison to the normal liver tissues, the chronic hepatitis C cases also revealed a significantly (p < 0.05) lower G1 (91 +/- 5) and a higher S (5.4 +/- 3.6) fraction, though staying behind the values found for the non-viral group. The deviation can be explained by the presentation of the HCV proliferation inhibitory effect. The polyploid cell fraction revealed a significantly higher value in the chronic non-viral cases as compared to the C virus group, reflecting on the decreased regeneration capacity of the liver. When comparing the HCV groups, significant differences were found between the mild and moderate cases in respect to the G1 and G2 fractions. At the same time, the moderate and severe cases showed statistical deviation regarding the DNA index. Chronic hepatitis C virus infection reduces the proliferation of hepatocytes and the regeneration capacity of the liver. The aneuploid DNA index reflects on genetic instability, which could be the basis of the malignant transformation of the cells.

Adult↗
PubMed2006

[Application of complete audiological evaluation battery in early hearing aid fitting for deaf children].

OBJECTIVE: To investigate the function of ABR and behavioral test battery in verifying the fitting of hearing aids on deaf children at early stage. METHOD: Fifty-two children of age 1 to 9 were examined with the behavioral test battery or ABR. Based on the hearing thresholds thus obtained, DSL prescriptive formula was used to verify the fitting of hearing aids. Real ear measurement and sound field test were employed to assess the benefit of hearing aid. The children were subsequently followed up on a regular basis. RESULT: There was statistic difference between ABR and behavioral test battery (P < 0.05). Forty-one deaf children demonstrated significant benefit from hearing aid fitting while 4 showed no measurable benefit. CONCLUSION: Both subjective and objective tests should be used for accurate hearing evaluation in deaf children. Hearing aid verification should be conducted accordingly. It is important to carry out early identification, intervention and rehabilitation.

Audiometry↗
PubMed1985

[Pathogenesis, clinical aspects and development of fatty liver].

Anamnestic, clinical, biochemical and bioptic examinations were performed in 127 patients with fatty infiltration of the liver of different degrees of severity. Anamnesis, clinical practice and laboratory findings can only throw the suspicion on the fatty infiltration of the liver. For the verification of the diagnosis and for the gradation first of all the liver biopsy is necessary. Alcohol clearly plays the most important part as a cause of the development of the fatty infiltration of the liver, followed by adiposity, diabetes and hyperlipoidaemia. Because of the great medical and social-economic importance fatty infiltration of the liver cannot longer be taken for a harmless disurbance.

Adult↗
PubMed2002

NotI flanking sequences: a tool for gene discovery and verification of the human genome.

A set of 22 551 unique human NotI flanking sequences (16.2 Mb) was generated. More than 40% of the set had regions with significant similarity to known proteins and expressed sequences. The data demonstrate that regions flanking NotI sites are less likely to form nucleosomes efficiently and resemble promoter regions. The draft human genome sequence contained 55.7% of the NotI flanking sequences, Celera's database contained matches to 57.2% of the clones and all public databases (including non-human and previously sequenced NotI flanks) matched 89.2% of the NotI flanking sequences (identity > or =90% over at least 50 bp, data from December 2001). The data suggest that the shotgun sequencing approach used to generate the draft human genome sequence resulted in a bias against cloning and sequencing of NotI flanks. A rough estimation (based primarily on chromosomes 21 and 22) is that the human genome contains 15 000-20 000 NotI sites, of which 6000-9000 are unmethylated in any particular cell. The results of the study suggest that the existing tools for computational determination of CpG islands fail to identify a significant fraction of functional CpG islands, and unmethylated DNA stretches with a high frequency of CpG dinucleotides can be found even in regions with low CG content.

Cell Line, Transformed↗
PubMed2006

Stress in caregivers of demented people in Korea--a modification of Pearlin and colleagues' stress model.

OBJECTIVES: We investigated the influence of demented people's function and caregiver burden on caregivers' psychological distress. Based on a modified model of Pearlin and colleagues (1990), we assessed the stress of demented people's caregivers in Korea. METHODS: A total of 122 demented people and their caregivers participated in this study. We evaluated dementia severity by the Clinical Dementia Rating (CDR), and caregivers reported their objective and subjective stressors. Objective stressors are the demented people's functional deterioration and behavioral problems, and subjective stressors are caregivers' reaction to objective stressors and the subjective burden in caregiving. The overall psychological distress of caregivers was evaluated by the Beck Depression Inventory (BDI) and the Spielberger Trait Anxiety Inventory-State (STAI-S). RESULTS: There were significant differences in both objective and subjective stressors according to the severity of dementia, but there was no significant difference in caregivers' psychological distress. The goodness-of-fit evaluation model showed the coping and social support variables affected the psychological distress as mediator variables (df = 109, chi (2) = 209.75, NFI = 0.949, RFI = 0.929, IFI = 0.975, TLI = 0.964, RMSEA = 0.087). CONCLUSION: The model suggests that psychological distress of caregivers is related to diverse variables, such as objective and subjective stressors, coping, and social support. This study provides verification of the modified model of Pearlin and coworkers in Koreans, and lays a foundation for practical use and further study.

Alzheimer Disease↗
PubMedDate not supplied

[Value of ultrasound examination in lesion of the medial collateral ligament of the knee joint].

AIM: The present prospective clinical study investigates the value of ultrasonic examination of injuries of the medial collateral ligament of the knee. METHOD: The sonographical examination was done in a real-time method with an ultrasound unit Type AI 3200 (Dornier, Neufahrn, Germany) and with a linear transducer (frequency 7.5 Mhz). This functional measurement is being performed in neutral position and in valgus stress on both knee joints to verify the opening of the medial joint space. 42 patients who have been suspicious for a lesion of the medial collateral ligament of the knee were compared with 80 healthy persons. RESULTS: The average medial opening of the medial joint space in the patient group using manual dynamic ultrasonic examination was 4.4 mm +/- 1.1 mm (2.5-8.0) applying the force manual and 4.0 mm 1.0 mm (1.3 mm-8.0) using the Telos fixation device to apply the stress force. The control group showed an average medial opening of 2.2 mm +/- 0.5 (0-0.5) as stress was applied manual and 2.5 mm +/- 0.7 mm (0-0.4) with the apparative stress examination using the Telos fixation device. CONCLUSION: The ultrasonic verification of the stability of the medial collateral ligament complex in the medial longitudinal view using defined bony landmarks is a very reliable method as a diagnostic tool for acute or older lesions of the medial collateral ligament of the knee. CLINICAL RELEVANCE: The advantages of the ultrasonic examination are the immediate availability, the avoidance of radiation and the visualization of movements with dynamic examinations. In contrast to X-ray examination the ultrasonic investigation can provide useful additional information on soft tissue structures.

Adolescent↗
PubMed1991

The role of heat-shock and chaperone proteins in protein folding: possible molecular mechanisms.

Recently some heat-shock proteins have been linked to functions of 'chaperoning' protein folding in vivo. Here current experimental evidence is reviewed and possible requirements for such an activity are discussed. It is proposed that one mode of chaperone action is to actively unfold misfolded or badly aggregated proteins to a conformation from which they could refold spontaneously; that improperly folded proteins are recognized by excessive stretches of solvent-exposed backbone, rather than by exposed hydrophobic patches; and that the molecular mechanism for unfolding is either repeated binding and dissociation ('plucking') or translocation of the protein backbone through a binding cleft ('threading'), allowing the threaded chain to refold spontaneously. The observed hydrolysis of ATP would provide the energy for active unfolding. These hypotheses can be applied to both monomeric folding and oligomeric assembly and are sufficiently detailed to be open to directed experimental verification.

Heat-Shock Proteins↗
PubMed1988

Vaso-occlusion in sickle cell disease: pathophysiology of the microvascular circulation.

Microvascular dysfunction accounts for the major morbidity and contributes to the mortality among patients with sickle cell hemoglobinopathies. We summarize the microcirculatory dynamics of red cells in sickle cell disease. An overview of the physiological attributes of the microcirculation is presented. The microcirculatory module is a unique organic entity within the tissue domain, which is concerned with the functional exchange of substances between the blood and the tissue environment. The impairment in deformability of sickle red cells and their heterogeneity cause them to show abnormal microvascular flow dynamics that, in turn, contribute to derangement of the microvascular bed. Studies of experimental models in animals have employed the microcirculation of the mesentery, the cremaster muscle, and the mesoappendix. These studies showed the rheological disequilibrium that results as sickle cells course through successive segments of the arterioles, capillaries, and venules. Direct in vivo microscopic observations in human subjects, with analysis and quantitation of the nailfold and bulbar conjunctival capillaries, have also provided useful information as to the adverse effects of sickling on the microcirculation. Sickle cell vaso-occlusion has three phases--initiation, propagation, and resolution. This framework provides a basis for testable hypotheses for verification in appropriately designed experiments. In this context, the determinants of the microvascular flow of erythrocytes in sickle cell disease are emphasized.

Anemia, Sickle Cell↗
PubMed2006

Quality control for digital mammography in the ACRIN DMIST trial: part I.

The Digital Mammography Imaging Screening Trial, conducted by the American College of Radiology Imaging Network, is a clinical trial designed to compare the accuracy of full-field digital mammography (FFDM) versus screen-film mammography in a screening population. Five FFDM systems from four manufacturers (Fischer, Fuji, General Electric, and Lorad) were employed in the study at 35 clinical sites. A core physics team devised and implemented tests to evaluate these systems. A detailed description of physics and quality control tests is presented, including estimates of: mean glandular dose, modulation transfer function (MTF), 2D noise power spectra, and signal-to-noise ratio (SNR). The mean glandular doses for the standard breast ranged from 0.79 to 2.98 mGy, with 1.62 mGy being the average across all units and machine types. For the five systems evaluated, the MTF dropped to 50% at markedly different percentages (22% to 87%) of the Nyquist limit, indicating that factors other than detector element (del) size have an important effect on spatial resolution. Noise power spectra and SNR were measured; however, we found that it was difficult to standardize and compare these between units. For each machine type, the performance as measured by the tests was very consistent, and no predictive benefit was seen for many of the tests during the 2-year period of the trial. It was found that, after verification of proper operation during acceptance testing, if systems failed they generally did so suddenly rather than through gradual deterioration of performance. Because of the relatively short duration of this study further, investigation of the long-term failure characteristics of these systems is advisable.

Algorithms↗
PubMed1997

The internal mammary artery malperfusion syndrome: late angiographic verification.

BACKGROUND: Here we report our experience with the incidence and the surgical treatment of the internal mammary artery (IMA) malperfusion syndrome, evaluate the predictive role of previously described risk factors for the syndrome, and assess the late patency of IMA grafts in patients in whom an IMA malperfusion syndrome was diagnosed and treated by additional saphenous vein grafting of the left anterior descending coronary artery. METHODS: From June 1992 to November 1995, 969 IMAs were anastomosed to the left anterior descending coronary artery system. In 11 patients, IMA malperfusion syndrome was diagnosed and treated by additional saphenous vein grafting of the LAD. There were 8 men and 3 women with a mean age of 58.9 years. The angiographic and clinical data for each patient were reviewed, and all but 1 surviving patient underwent late angiographic control (mean follow-up, 18 months; range, 4 to 46 months). RESULTS: One patient died in the hospital. No previously described risk factor was strongly associated with the occurrence of IMA malperfusion syndrome. Late angiography revealed a malfunctioning IMA graft in 7 of the 9 patients. A string sign was observed in 1 patient and a normally functioning IMA anastomosed to a diagonal branch not connected to the LAD, in another. In no patient was a widely patent and normally functioning IMA graft observed. CONCLUSIONS: In our series, a high proportion of IMA grafts were found to be malfunctioning at late angiography. This observation, in contrast to previous reports, suggests that IMA malperfusion syndrome can often be attributable to technical problems in harvesting the IMA or in performing the IMA anastomosis. Functional IMA insufficiency seems to play only a marginal role in determining the IMA malperfusion syndrome.

Coronary Angiography↗