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PubMed2006

Analysis of biomedical signals by the lempel-Ziv complexity: the effect of finite data size.

The Lempel-Ziv (LZ) complexity and its variants are popular metrics for characterizing biological signals. Proper interpretation of such analyses, however, has not been thoroughly addressed. In this letter, we study the the effect of finite data size. We derive analytic expressions for the LZ complexity for regular and random sequences, and employ them to develop a normalization scheme. To gain further understanding, we compare the LZ complexity with the correlation entropy from chaos theory in the context of epileptic seizure detection from EEG data, and discuss advantages of the normalized LZ complexity over the correlation entropy.

Algorithms↗

PubMed2003

Cerebral MR venography of transverse sinuses in subjects with normal CSF pressure.

Flow artifacts or anatomic variants of venous sinuses often make MR venography (MRV) interpretation difficult. The authors investigated cerebral MRV in 111 subjects with normal CSF pressure to identify the most common flow abnormalities of transverse sinuses (TS). Disturbance of venous outflow in one transverse sinus was commonly observed in 30% of subjects whereas flow abnormalities of both TS occurred in 2 of 111 individuals. Subjects with flow gaps in both TS should undergo lumbar puncture to exclude increased CSF pressure.

Adolescent↗

PubMed1987

Penile magnification pharmacoarteriography: details of intrapenile arterial anatomy.

To establish a base of normality against which state-of-the-art penile arteriograms can be assessed, we analyzed selective magnification penile pharmacoarteriograms from 23 men who were not believed to have arteriogenic impotence. The penile arteries showed no evidence of acquired obstructive disease, and all individuals had had normal sexual function in the recent past. The vascular patterns were highly variable and frequently differed from classic descriptions found in textbooks of anatomy. Normal variations that could be easily confused with arterial obstruction were unilateral origin of all cavernosal branches, unilateral hypoplasia of a dorsal penile artery, and aberrant origin of bulbar or cavernosal arteries. Multiple potential collateral routes were shown, including transverse collaterals at the root of the penis and communications between cavernosal and dorsal penile arteries. Appreciation of the type and frequency of anatomic variants and potential collateral routes is important in correctly interpreting penile angiograms and in evaluating the hemodynamic significance of suspected stenoses.

Arterial Occlusive Diseases↗

PubMed2001

[Tumor antigens presented to T helper lymphocytes--critical components of the cancer vaccine].

BACKGROUND: Due to acquired mutations, the protein composition of malignant tumours is distinct from that of normal cells to which the immune system is tolerant. Mobilisation of the patient's immune system against malignant cells remaining after conventional treatment is an attractive therapeutic option since lymphocytes respond with high sensitivity and specificity to non-self. MATERIAL AND METHODS: The potential of cancer vaccines targeted to T helper cells is discussed on the basis of published data including the author's studies. RESULTS: T helper cells kill cancer cells by direct cell-cell contact, stimulate other cytotoxic effector cells and respond to autologous tumour antigens like HER-2/neu (mammary and ovary cancer), tyrosinase (malignant melanoma), p21 ras (colorectal and pancreatic cancer), BCR-ABL (chronic myeloid leukaemia) and immunoglobulin (B-cell lymphoma). HER-2/neu and tyrosinase are not mutated, p21 ras and BCR-ABL represent a restricted set of mutations, and genetic variants of immunoglobulin can be characterised by hybridoma technology. INTERPRETATION: Targeted screening can, in a large number of cancer patients, identify peptide sequences potentially useful for therapeutic immunisation. Peptides can be designed to combine immunogenicity in the individual patient with proteolytic resistance, and are presently being tested as cancer vaccines.

Antigens, Neoplasm↗

PubMed2004

How important is a cardiac echogenic focus in a routine fetal examination?

UNLABELLED: Intracardiac echogenic foci are very frequent findings during routine fetal ultrasound examination and sometimes a reason for referral of patients for fetal echocardiography. OBJECTIVE: To assess the incidence of echogenic intracardiac foci in a mixed population of fetuses at high and low risk for congenital heart defects, and to determine whether the association between echogenic foci and congenital heart disease is stronger than in the general fetal population. DESIGN: Retrospective evaluation of clinical files at two fetal cardiology referral centers, during the last two years. All cases that had at least one echogenic focus were selected for our study. Maternal age, gestational age, reason for referral, location and number of echogenic foci, chromosomal abnormalities and cardiac defects were analyzed. As previous studies suggest increased risk of trisomy associated with echogenic foci and considering that congenital heart defects are more frequent in fetuses with trisomy 21, we excluded all fetuses with aneuploidy from our study. RESULTS: Thus, 753 clinical files were reviewed, of which 61 (8.1%) had a fetus with at least one echogenic focus. Mean maternal age was 29.0 years (minimum--19 years, maximum--43 years). Mean gestational age at the time of the examination was 23.4 weeks (minimum--19 weeks, maximum--31 weeks). In 48.0% the reason for referral for fetal echocardiography was the existence of echogenic foci previously seen during a routine maternal examination. Increased nuchal translucency in 13.0% of pregnant women, maternal age in 10.0%, family history of congenital heart defects in 8.4%, suspicion of cardiac malformation in the obstetric scan in 4.2%, twinning in 4.0%, history of miscarriage in 2.1% and maternal pathology in 10.3% were other referral reasons. In 53 cases a single echogenic focus was found, 44 of them inside the left ventricle and 9 in the right ventricle. Multiple echogenic foci were found in the different heart chambers in the eight remaining cases. Fifty-six fetuses had a structurally normal heart and in five (8.1%) a cardiac defect was found. CONCLUSION: Echogenic foci are commonly seen inside heart chambers during routine fetal heart scanning, the left ventricle being the most frequent location. Although they probably represent a normal variant of papillary muscle development their presence should be interpreted as a possible risk for congenital heart defects.

Adult↗

PubMed2004

Characterization of mild coagulation factor VII deficiency: activity and clearance of the Arg315Trp and Arg315Lys variants in the Cys310-Cys329 loop (c170s).

BACKGROUND AND OBJECTIVES: Arginine 315 in factor VII (FVII) belongs to a solvent-exposed loop involved in direct interaction with the co-factor (tissue factor, TF), in transmission of TF-induced effects and potentially in FVIIa inactivation. Natural FVII variants at position 315 provide peculiar models for structure-function studies. DESIGN AND METHODS: We characterized a mild coagulation FVII deficiency associated with reduced FVII activity (26%) and antigen (67%). Mutations were searched by FVII gene sequencing. FVII variants were created by mutagenesis of FVII cDNA and characterized through expression in HEK293 cells followed by functional studies. FVII antigen in media was estimated by immunoassay while FVII activity was assessed by prothrombin-time based and FXa generation assays. FVII variants were injected into mice to investigate their recovery and half-life. One-way ANOVA was used to test statistical significance. RESULTS: The patient was double heterozygous for a novel R315W mutation and for the R304Q substitution (FVII Padua) previously demonstrated to impair TF binding. The recombinant 315W-FVII was normally expressed in medium but showed a markedly reduced coagulant function (52%) and activity towards factor X (FX) in plasma (34%). Moreover, the 315W-FVII showed significantly decreased recovery of the protein (20%) and a slightly shorter half-life (8.6 min) as compared to wt-FVII (50% and 10.7 min). We also studied the conservative R315K change that was responsible for low recovery (20%) and a decreased half-life (7 min) of a FVII variant with virtually normal FVII antigen and activity levels. INTERPRETATION AND CONCLUSIONS: These findings suggest a dual role of R315 for FVII function and clearance, and indicate that substitutions at this position have appreciable effects on human FVII biology, compatible with residual FVII function and thus with mild FVII deficiency.

Adult↗

PubMed1990

[The morphological diagnosis of malignant non-Hodgkin's lymphomas (lymphosarcomas)].

On the basis of morphoimmunological correlates certain criteria have been elaborated helpful in diagnosis of non-Hodgkin's malignant lymphomas (NML) of both B- and T-cell origin, and this was reflected in the modified Kiel's classification. The group of T-cell NML has considerably increased. T-cell origin of Lennert's lymphoma and angioimmunoblastic lymphadenopathy has been proven. Morphological substrate of NML from peripheral T-lymphocytes became more precise. The tumours, depending on the predominant cells, are subdivided into small cell (T-zones and pleomorphic lymphoma of small cells), mixed cell (pleomorphic lymphoma of medium-size and large cells) and large cell lymphoma (immunoblastic and large cell anaplastic Ki-I+). Criticism of T-NML systematization is due to the lack of definite cytological criteria because of the extreme morphological heterogeneity of peripheral T-lymphocytes and different interpretation of the clinical course of the established morphological variants. Among B-cell lymphomas the problem of the so-called intermediate lymphocytic lymphoma (ILL) and its variety--a mantle-zone lymphoma as well as monocytoid B-cell lymphoma is discussed in the literature. It is established in immunological testing that the cells of ILL possess a phenotype of cells of the primary follicles and those of the mantle-zone of the secondary follicles while the cells of the monocytoid B-cell NML have a peculiar unique phenotype similar to that of cells in the marginal zone of the spleen follicles.

Humans↗

PubMed1987

[A data processing system for bacteriological and chemical water analysis].

Using the "Natural" computer language a menu-guided system for cataloguing, processing and evaluating bacteriological and chemical water analyses was designed. The program can be employed to different blocs of analyses, e.g. "TrinkwV"-analyses, standard-analyses, those on volatile chlorinated hydrocarbons and bacteriological water analyses as well. For each water sample the actual, the last and the next to the last value, also arithmetical means, minimal and maximal are stored and can be retrieved. The evaluation of the bacteriological analyses and those of the volatile chlorinated hydrocarbons is carried out by a choice of text variants, whereas the TVO- and standard-analyses are interpreted automatically. Managing laboratory data has become much easier during our three years experience using this system for information storage, search and retrieval in water research and routine; even untrained users are able to handle it after a short period of tuition.

Bacteria↗

PubMed1983

Monoclonal antibodies against the G1 and nucleocapsid proteins of LaCrosse and Tahyna viruses.

Monoclonal antibodies against the Gl (glycoprotein) and Nc (nucleocapsid) proteins of LaCrosse (LAC) and Tahyna (TAH) viruses were generated using a standard protocol. Monoclonal antibodies against Gl were either neutralizing or non-neutralizing, and there was close concordance between inhibition of hemagglutination and neutralizing activities. The LAC virus neutralizing antibodies could be further subdivided into strain-specific and cross-reactive groups on the basis of both neutralization and inhibition of hemagglutination. These data support the concept of a glycoprotein molecule with three antigenic sites, two involved in neutralization and hemagglutination, and an additional site with no biological function as yet defined. Preliminary information from LAC virus variants selected with these monoclonal antibodies agrees with this interpretation. Anti Nc antibodies were all cross-reactive in an ELISA assay. Patterns of monoclonal cross-reactivity against California serogroup viruses are compared with the currently accepted antigenic relationships.

Antibodies, Monoclonal↗

PubMed1995

[Lactate dehydrogenase (LDH)].

The quantitative distribution of the lactate dehydrogenase (LDH) isozymes is different and characteristic. Therefore, when the LDH isozymes are released from tissue to serum, as on cell injury, the serum LDH isozyme pattern changes and in a sense resembling the profile of the affected tissue. However, the serum LDH isozyme pattern often differs from the isozyme pattern in the original tissues because of differing individual isozyme elimination rates. On the contrary, we should be able to determine the origin of enzyme release, disease stage and prognosis. The LDH isozyme pattern is sometimes modified by various factors, such as LDH-immunoglobulin complex or genetic variants. Results of isozyme determinations must therefore be carefully interpreted with a knowledge of biochemistry, physiology and limitation.

Clinical Enzyme Tests↗

PubMed1995

"Pseudoneoplastic" leprosy. Leprosy revisited.

A 70-year-old Italian man with a history of squamous cell carcinoma of the lung presented with a nodular skin eruption. He had traveled extensively in India and Sri Lanka. The nodules were well demarcated and measured up to 3.5 cm in diameter. Histologically, there was a proliferation of spindled and polygonal cells with focal and relatively inconspicuous cytoplasmic vacuolation. A macrophage-monocyte lineage for the cells was confirmed by paraffin section immunohistochemistry, using the monoclonal antibodies anti-CD45, MAC-387, KP-1, UCHL-1, MT-1, L26, and MB2. Infiltrating borders, extension of the lesion into the subcutis, and involvement of small dermal nerves and eccrine glands initially suggested the possibility of a "histiocytic" neoplasm of indeterminate biological potential. However, air-dried and Giemsa-stained material from a fine-needle aspirate of one cutaneous nodule showed needle-shaped intracellular "negative images," and acid-fast stains revealed a large number of intracytoplasmic bacilli in virtually all of the vacuolated lesional cells. Furthermore, a second skin nodule that was excised 3 weeks after initial presentation showed the typical morphology of lepromatous leprosy. The clinicopathologic features of this case demonstrated several similarities with those of so-called "histoid" leprosy. Unusual morphologic variants of leprosy need to be considered in the interpretation of unusual "histiocytic" infiltrates in order to avoid a mistaken diagnosis of neoplasia, regardless of the geographic locale in which the patient is evaluated.

Aged↗

PubMed1997

[Glycosylated hemoglobin and glycosylated proteins for metabolic control of diabetes mellitus].

The target of therapy in patients with diabetes mellitus is preventing the development of late complications due to nearly normal blood glucose values. For the diagnosis and control of therapy in routine management of diabetes mellitus, determination of glycated haemoglobin (HbA1c) and fructosamine in addition to blood glucose values are of equal importance. This report stresses the clinical use, standard-determination methods and interpretation of glycated protein values. The problems of haemoglobin variants detected in Austria interfering with determination of HbA1c using the high performance liquid chromatography method and the suggestions of the American Diabetes Association for using glycated haemoglobin and fructosamine are discussed as well.

Blood Glucose↗

PubMed2004

Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant.

BACKGROUND: Highly publicised outbreaks of norovirus gastroenteritis in hospitals in the UK and Ireland and cruise ships in the USA sparked speculation about whether this reported activity was unusual. METHODS: We analysed data collected through a collaborative research and surveillance network of viral gastroenteritis in ten European countries (England and Wales were analysed as one region). We compiled data on total number of outbreaks by month, and compared genetic sequences from the isolated viruses. Data were compared with historic data from a systematic retrospective review of surveillance systems and with a central database of viral sequences. FINDINGS: Three regions (England and Wales, Germany, and the Netherlands) had sustained epidemiological and viral characterisation data from 1995 to 2002. In all three, we noted a striking increase in norovirus outbreaks in 2002 that coincided with the detection and emergence of a new predominant norovirus variant of genogroup II4, which had a consistent mutation in the polymerase gene. Eight of nine regions had an annual peak in 2002 and the new genogroup II4 variant was detected in nine countries. Also, the detection of the new variant preceded an atypical spring and summer peak of outbreaks in three countries. INTERPRETATION: Our data from ten European countries show a striking increase and unusual seasonal pattern of norovirus gastroenteritis in 2002 that occurred concurrently with the emergence of a novel genetic variant. In addition to showing the added value of an international network for viral gastroenteritis outbreaks, these observations raise questions about the biological properties of the variant and the mechanisms for its rapid dissemination.

Caliciviridae Infections↗

PubMed1994

Comparison of three different recombinant hepatitis B virus core particles expressed in Escherichia coli.

The properties of three different recombinant hepatitis B virus core proteins expressed in Escherichia coli were compared: an N-terminal fusion protein, a C-terminally truncated protein and a sequence-authentic protein. All three proteins assembled into capsid-like particles with typical HBc-antigenicity, sedimentation behavior and distinctive electron microscopical images. Apart from this, however, variant HBc proteins displayed properties different from sequence-authentic HBc protein p21.4. Unlike p21.4, the particles of the N-terminal fusion protein p22.2 were sensitive to proteolytic attack by trypsin at variable sites within its arginine-rich C-terminus but not in its extended N-terminus. We therefore conclude that the C-terminal region is located on the surface of the p22.2 particle. These particles also showed increased HBe-antigenicity, as did the C-terminally truncated core particles p17.6, and to an even greater extent p18* particles which were derived from p22.2 by tryptic digestion. This might be interpreted as evidence for an--albeit minor--structural change. All variant core particles were less stable and contained less RNA. Electron microscopic indication for DNA binding of C-terminal deleted p17.6 particles was obtained using an aqueous spreading technique.

Amino Acid Sequence↗

PubMed2004

Recombinant fibrinogen, gamma275Arg-->Cys, exhibits formation of disulfide bond with cysteine and severely impaired D:D interactions.

BACKGROUND AND OBJECTIVES: Analysis of dysfibrinogens has provided useful information aiding our understanding of molecular defects in fibrin polymerization. We have already reported impaired fibrin polymerization in a variant fibrinogen (gammaArg275Cys), the Cys being located in the D:D interface. Since this substitution occurred in a heterozygous individual, interpretation of the functional analysis was complicated. We tried to resolve this complication by synthesizing a recombinant variant fibrinogen. METHODS: A variant gamma-chain expression plasmid was transfected into Chinese hamster ovary cells expressing normal human fibrinogen Aalpha- and Bbeta-chains. The recombinant variant fibrinogen (gamma275C) was purified using an immunoaffinity column, and we compared its structure and functions with those of normal recombinant fibrinogen (gamma275R) and plasma variant fibrinogen. RESULTS: Mass analyses showed the existence of disulfide-linked Cys in both patient and recombinant variant fibrinogens. Functional analyses indicated that both fibrin polymerization and gamma-gamma dimer formation were markedly impaired in the variant fibrinogen. The impairments were much more pronounced in gamma275C than in plasma variant fibrinogen. In addition, scanning electron microscopic observation of fibrin clots made from gamma275C revealed less dense fibrin fiber bundles and larger fiber diameter than in those made from gamma275R, and also the existence of many aberrant fibrin fibers with tapered ends. CONCLUSIONS: These results indicate that gammaArg275 has an important residue affecting the structure and function of the gamma-chain C-terminal domain. However, the variant D:D interface can interact with that of the normal fibrinogen existing in a heterozygous patient with dysfibrinogenemia.

Amino Acid Substitution↗

PubMedDate not supplied

[Correlations between conventional allergometry and the Palmer types in interpretation of tuberculin skin tests].

In view of differentiating post-vaccinal allergy from that developing after tuberculosis infection, the authors have investigated comparatively intradermal-reactions to tuberculin according to classical allergometry, and to the 4 types described by Palmer-Edwards in a group of 1549 students and 211 patients. All the subjects were tested with 2 units of PPD IC 65. It was noted that the type I and II Palmer reactions corresponded, in the majority of the cases, to intense, or hyperergic ID reactions, while the types III and IV of Palmer corresponded to slightly positive, or to negative ID reactions. The presence of the post-vaccinal scar does not appear to influence significantly the type of the reaction, but the presence of active specific lesions is accompanied by reactions of type I and II of the Palmer classification. It is concluded that although the Palmer types do not allow to make a clear differentiation between the two variants of allergy they provide however useful indications for the interpretation of IDR in a more sophisticated manner, as compared with the conventional allergometry.

Adolescent↗

PubMed1985

Procedure for characterization of creatine kinase variants on agarose electrophoretograms.

Electrophoretograms of atypical creatine kinase (EC 2.7.3.2, CK) isoenzymes may be difficult to interpret. In addition, their presence may cause discrepancies between results by immunological determinations for mass or activity and those by electrophoresis. Here we outline procedures to use in characterizing apparently atypical CK isoenzymes observed after electrophoresis, as illustrated by a CK isoenzyme variant that migrated as CK-MB.

Creatine Kinase↗

PubMed1998

Screening of a highly polymorphic microsatellite for microheterogeneity in human identification.

Single-strand conformation polymorphism (SSCP) analysis combined with automated laser fluorescence detection is proposed as a comprehensive, rapid and sensitive method for screening sequence variation of the human beta-actin-related pseudogene (HUMACTBP2). Eleven sequenced alleles representing each type of known sequence variant of HUMACTBP2 locus were studied. Allelic variants of the same size but different sequence structures are easily resolved on the basis of their secondary conformation. Fifty ACTBP2 amplification products previously typed on a denaturing gel were repeatedly examined to determine the utility of SSCP analysis in terms of ease of interpretation and reproduction capabilities of the conformational patterns. Eleven sequenced ACTBP2 allelic variants were used as external conformation standards in polymerase chain reaction (PCR)-SSCP subtyping. This enabled identification of polymorphism in a particular length variant and therefore consistent discrimination between heterozygous samples appeared identical on denaturing gels. Of five "homozygous" samples, one was shown to be heterozygous for two distinct alleles of the same size but different sequences. Thus, the method provides a unique possibility for detecting false homozygotes. The technique complements both denaturing gel electrophoresis and DNA sequencing in studies on the overall variability of the ACTBP2 locus.

Actins↗