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Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 109 records · Page 6Linked to original sources
PubMed2000

Texture analysis for classification of cervix lesions.

This paper presents a generalized statistical texture analysis technique for characterizing and recognizing typical, diagnostically most important, vascular patterns relating to cervical lesions from colposcopic images. The contributions of the research include: 1) the introduction of a generalized texture analysis technique based on the combination of the conventional statistical and structural textural analysis approaches by using a statistical description of geometric primitives; 2) the introduction of a set of textural measures that capture the specific characteristics of cervical textures as perceived by human. Experimental study with real images demonstrated the feasibility and promising of the proposed approach in discriminating between cervical texture patterns indicative of different stages of cervical lesions.

Female↗
PubMed2000

Chronic epileptogenesis requires development of a network of pathologically interconnected neuron clusters: a hypothesis.

PURPOSE: The "silent period" is a characteristic of human localization-related symptomatic epilepsy. In mesial temporal lobe epilepsy (MTLE), it follows an initial precipitating injury, and in animal models of MTLE in which brain damage is artificially created, there is also a prolonged interval between injury and the onset of spontaneous seizures. The neuronal reorganization responsible for epileptogenesis presumably takes place during this silent interval; however, the functional correlates of this process are poorly understood. We have previously described high-frequency (250 to 500 Hz) oscillations, called fast ripples (FR), in the hippocampus and entorhinal cortex (EC) of intrahippocampal kainic acid (KA)-injected rats and patients with MTLE that are confined to the region of spontaneous seizure generation. We have proposed, therefore, that FR reflect the mechanisms responsible for epileptogenesis. If this is the case, they should appear during the process of epileptogenesis, before the appearance of spontaneous seizures. The purpose of the present study was to record continuously from rats after KA injection to compare the temporal development of FR with spontaneous seizures. Additional goals were to determine in these rats after spontaneous seizures begin (a) the volume of tissue in which FR can be recorded in hippocampus and EC, (b) the multiple-unit and field potential correlates of FR oscillations, and (c) whether there is an association of FR with mossy fiber sprouting. METHODS: After unilateral KA injection in the posterior hippocampus, interictal field epileptic activity and single-unit activity were recorded from freely moving animals using multiple-contact microelectrodes in dentate gyrus (DG) and EC. One group of animals underwent continuous recording to determine the time of onset of both FR oscillations and spontaneous seizures. A second group was implanted after behavioral seizures began to measure the area within which FR could be recorded as well as their unit and field potential correlates. The neo-Timm method was used to reveal mossy fiber sprouting, and gray value analysis was used to measure the intensity of sprouting in the inner molecular layer of DG. RESULTS: In KA-injected rats, FR were observed in hippocampal areas adjacent to the lesion and in the ipsilateral EC 11 to 14 days after injection, whereas spontaneous behavioral seizures occurred 2 to 4 months after injection. Analysis of depth profiles of interictal FR in the DG and EC showed that they were generated in local areas with a volume of about 1.0 mm3, and unit recordings indicated that they reflected fields of hypersynchronous action potentials. FR were found in areas of DG with more intensive mossy fiber sprouting. However, the correspondence was not absolute. CONCLUSIONS: The electrophysiological and anatomical data are consistent with the participation of FR oscillations, within small neuronal assemblies, in the development of chronic epileptogenesis. It is hypothesized that small clusters of pathologically interconnected neurons develop after focal hippocampal injury and that these clusters are capable of generating powerful hypersynchronous bursts of action potentials, which initiate epileptogenesis via a kindling effect. As the silent period progresses, a network of such clusters is formed that allows the development of discharges that spread throughout the limbic system. When this network engages brain areas that control motor activity, clinical seizures occur and the silent period ends.

Action Potentials↗
PubMed2000

Long term follow up of premature infants: detection of strabismus, amblyopia, and refractive errors.

AIM: To establish recommendations for long term ophthalmological follow up of prematurely born infants. METHODS: 130 infants with a gestational age (GA) <37 weeks and born between 1 November 1989 and 31 October 1990 were enrolled in a prospective study about the development of strabismus, amblyopia, and refractive errors. Infants were subdivided in three groups according to GA: A <28 weeks (n=32), B >/=28-</=32 weeks (n=64), C >32-<37 weeks (n=34). Ophthalmological assessment took place at the postconceptional age of 32 weeks, at term and at 3, 6, 12, and 30 months post term. At the age of 5 years parents received a questionnaire and a majority of the children was examined again (n=99). RESULTS: At the age of 5 years 46 infants were known to have strabismus (n=29) and/or amblyopia (n=22) and/or refractive errors (n=22). Statistical analysis showed that gestational age, duration of supplementary oxygen, and duration of hospitalisation were important predictive variables for the development of strabismus, amblyopia, or refractive errors (SAR) at the age of 5 years (p<0.05). Infants with a GA </=32 weeks had a significantly higher risk of developing SAR than infants with a GA >32 weeks, who developed an incidence comparable with the normal population. Strabismus developed mainly in the first year of life and at the age of 5 years. Most infants with amblyopia were detected at the age of 2-3 years. Refractive errors were found in the first year of life and at the age of 2.5 and 5 years. CONCLUSION: Infants with a GA <32 weeks should be selected for long term ophthalmological follow up. These infants should be screened at the age of 1 year, in the third year of life (preferably at 30 months), and just before school age (including testing of visual acuity with optotypes).

Amblyopia↗
PubMed2000

Functional and anatomic correlates of two frequently observed temporal lobe seizure-onset patterns.

Intracranial depth electrode EEG records of 478 seizures, recorded in 68 patients undergoing diagnostic monitoring with depth electrodes, were evaluated to investigate the correlates of electrographic onset patterns in patients with temporal lobe seizures. The seizure onsets in 78% of these patients were identified as either hypersynchronous onsets, beginning with low-frequency, high-amplitude spikes, or low-voltage fast (LVF) onsets, increasing in amplitude as the seizure progressed. The number of patients (35) having hypersynchronous seizure onsets was nearly twice that of patients (18) having LVF onsets. Three major differences were seen among patients with the two seizure-onset patterns. When compared with patients having LVF onsets, patients with hypersynchronous seizure onsets had a significantly greater probability of having (1) focal rather than regional seizure onsets (p < 0.01), (2) seizures spreading more slowly to the contralateral mesial temporal lobe (p < 0.003), and (3) cell counts in resected hippocampal tissue showing greater neuronal loss (p < 0.001). The results provide evidence that the most frequent electrographic abnormality associated with mesial temporal seizures is local hypersynchrony, a condition associated with major neuronal loss in the hippocampus. The results also indicate that LVF seizure onsets more frequently represent widely distributed discharges, which interact with and spread more rapidly to surrounding neocortical areas.

Adolescent↗
PubMed2000

Loteprednol etabonate: a soft steroid for the treatment of allergic diseases of the airways.

There are several approaches for developing new antiallergic/antiasthmatic agents. One of them is the improvement of an existing class of effective drug classes. Due to some undesired effects of intranasal or inhaled corticosteroids, there is a need for better tolerated corticosteroids. Loteprednol etabonate belongs to the so-called class of soft steroids because it is metabolized by a one-step reaction (hydrolysis) without using the cytochrome P450 monooxygenase system. In in vitro investigations using human cells, loteprednol inhibited the release of proinflammatory cytokines (e.g., TNF-alpha, GM-CSF, IL-4, IL-5) according to its relative binding potency to the glucocorticoid receptor. In in vivo animal studies, loteprednol effectively inhibited allergically induced vascular leakage in the nasal cavity of actively sensitized Brown Norway rats and rhinorrhea in actively sensitized domestic pigs following nasal challenge. In several models of allergic asthma, it was clearly demonstrated that loteprednol was able to suppress the allergically induced late phase eosinophilia in mice, rats and guinea pigs. After intrapulmonary administration of loteprednol, only a slight, statistically nonsignificant reduction in thymus weight was observed in a dose range far less than the therapeutically relevant doses. Its therapeutic ratio is clearly superior to those of beclomethasone and budesonide. Loteprednol is a safe steroid with an extremely wide range between therapeutic and side effect inducing doses. Its elimination profile, its pronounced binding to plasma protein and erythrocytes and the low oral bioavailability makes this drug highly suitable for nasal or pulmonary use.

Journal Article↗
PubMed2000

Disposition and metabolism of cetrorelix, a potent luteinizing hormone-releasing hormone antagonist, in rats and dogs.

Disposition and metabolism of cetrorelix was studied in intact and bile duct-cannulated rats and dogs after s.c. injection. An s.c. dose of 0.1 mg/kg [(14)C]cetrorelix was rapidly and completely absorbed in rats. T(max) in plasma and most tissues was at 2 h. Radioactivity at the injection site in rats declined to 10% by 24 h. The extent of (14)C absorption in rats calculated from excretion until 264 h was 94%. Exposure of the target organ pituitary gland was demonstrated with a time course similar to plasma but on a higher level. Rats excreted 69.6% of radioactivity via feces and 24. 3% into urine. Excretion was nearly complete within 48 h. No enteral reabsorption was detected. In dogs t(max) in plasma was 1.3 h. (14)C- and cetrorelix-plasma levels were similar until 24 h, indicating a negligible amount of metabolites. A dose of 1 mg/kg in dogs showed an increasing influence of a slow absorption phase (flip-flop). In dogs equal amounts of the (14)C dose were found within 192 h in feces and urine, 46 and 48%, respectively. In urine of both species, only intact cetrorelix was detected. In bile and feces of both species qualitatively the same metabolites were found, characterized as truncated peptides of the parent decapeptide. The major metabolite occurring in bile of both species was the (1-7)heptapeptide. The amounts of the (1-4)tetrapeptide in feces of rats but not in that of dogs increase with time, suggesting additional degradation of the peptide in the gastrointestinal tract of rats by enteric metabolization.

Absorption↗
PubMed1999

Deposition of Oral Bacteria and Polystyrene Particles to Quartz and Dental Enamel in a Parallel Plate and Stagnation Point Flow Chamber.

The aim of this paper is to determine to what extent (i) deposition of oral bacteria and polystyrene particles, (ii) onto quartz and dental enamel with and without a salivary conditioning film, (iii) in a parallel plate (PP) and stagnation point (SP) flow chamber and at common Peclet numbers are comparable. All three bacterial strains showed different adhesion behaviors, and even Streptococcus mitis BMS, possessing a similar cell surface hydrophobicity as polystyrene particles, did not mimic polystyrene particles in its adhesion behavior, possibly as a result of the more negative zeta potentials of the polystyrene particles. The stationary endpoint adhesion of all strains, including polystyrene particles, was lower in the presence of a salivary conditioning film, while also desorption probabilities under flow were higher in the presence of a conditioning film than in its absence. Deposition onto quartz and enamel surfaces was different, but without a consistent trend valid for all strains and polystyrene particles. It is concluded that differences in experimental results exist, and the process of bacterial deposition to enamel surfaces cannot be modeled by using polystyrene particles and quartz collector surfaces. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Interaction of agrin with laminin requires a coiled-coil conformation of the agrin-binding site within the laminin gamma1 chain.

Coiled-coil domains are found in a wide variety of proteins, where they typically specify subunit oligomerization. Recently, we have demonstrated that agrin, a multidomain heparan sulfate proteoglycan with a crucial role in the development of the nerve-muscle synapse, binds to the three-stranded coiled-coil domain of laminin-1. The interaction with laminin mediates the integration of agrin into basement membranes. Here we characterize the binding site within the laminin-1 coiled coil in detail. Binding assays with individual laminin-1 full-length chains and fragments revealed that agrin specifically interacts with the gamma1 subunit of laminin-1, whereas no binding to alpha1 and beta1 chains was detected. By using recombinant gamma1 chain fragments, we mapped the binding site to a sequence of 20 residues. Furthermore, we demonstrate that a coiled-coil conformation of this binding site is required for its interaction with agrin. The finding that recombinant gamma1 fragments bound at least 10-fold less than native laminin-1 indicates that the structure of the three-stranded coiled-coil domain of laminin is required for high-affinity agrin binding. Interestingly, no binding to a chimeric gamma2 fragment was observed, indicating that the interaction of agrin with laminin is isoform specific.

Agrin↗
PubMed1999

Heterodimerization of a functional GABAB receptor is mediated by parallel coiled-coil alpha-helices.

A detailed understanding of GABAB receptor assembly is an important issue in view of its role as attractive target for treatment of epilepsy, anxiety, depression, cognitive defects, and nociceptive disorders. Heteromerization of GABAB-R1 and GABAB-R2 subunits is a prerequisite for the formation of a functional GABAB receptor. Each individual subunit contains one stretch of approximately 30 amino acid residues within its intracellular C-terminal domain that mediates heteromer formation. To investigate the mechanism of the GABAB-R1/GABAB-R2 interaction and to assess the subunit stoichiometry of the complex, recombinant polypeptide chain fragments containing the heteromerization site were produced by heterologous gene expression in Escherichia coli. When mixed in equimolar amounts, these peptides preferentially formed parallel coiled-coil heterodimers under physiological buffer conditions. This demonstrates that the short C-terminal regions are sufficient to determine the specificity of interaction between GABAB receptor subunits. In contrast, isolated GABAB-R1 peptides folded into relatively unstable homodimers, whereas GABAB-R2 peptides were largely unstructured. Together with the data reported in the literature, the results presented here indicate that the functional GABAB receptor is a heterodimer assembled by parallel coiled-coil alpha-helices.

Adult↗
PubMed1999

Domain organization of Mac-2 binding protein and its oligomerization to linear and ring-like structures.

The multidomain Mac-2 binding protein (M2BP) is present in serum and in the extracellular matrix in the form of linear and ring-shaped oligomers, which interact with galectin-3, fibronectin, collagens, integrins and other large glycoproteins. Domain 1 of M2BP (M2BP-1) shows homology with the cysteine-rich SRCR domain of scavanger receptor. Domains 2 and 3 are related to the dimerization domains BTB/POZ and IVR of the Drosophila kelch protein. Recombinant M2BP, its N-terminal domain M2BP-1 and a fragment consisting of putative domains 2, 3 and 4 (M2BP-2,3,4) were investigated by scanning transmission electron microscopy, transmission electron microscopy, analytical ultracentrifugation and binding assays. The ring oligomers formed by the intact protein are comprised of approximately 14 nm long segments composed of two 92 kDa M2BP monomers. Although the rings vary in size, decamers predominate. The various linear oligomers also observed are probably ring precursors, dimers predominate. M2BP-1 exhibits a native fold, does not oligomerize and is inactive in cell attachment. M2BP-2,3,4 aggregates to heterogeneous, protein filled ring-like structures as shown by metal shadowed preparations. These aggregates retain the cell-adhesive potential indicating native folding. It is hypothesized that the rings provide an interaction pattern for multivalent interactions of M2BP with target molecules or complexes of ligands.

Amino Acid Sequence↗
PubMed1999

Characterization of recombinant human type IX collagen. Association of alpha chains into homotrimeric and heterotrimeric molecules.

As type IX collagen is a minor cartilage component, it is difficult to purify sufficient amounts of it from tissues or cultured cells to study its structure and function. Also, the conventional pepsin digestion used for fibrillar collagens cannot be utilized for purifying type IX collagen, because it contains several interruptions in its collagenous triple helix. A baculovirus expression system was used here to produce recombinant human type IX collagen by coinfecting insect cells with three viruses containing full-length cDNAs for the alpha1(IX), alpha2(IX), and alpha3(IX) collagen chains together with a double promoter virus for the alpha and beta subunits of human prolyl 4-hydroxylase. Correctly folded recombinant type IX collagen was secreted, consisting of the three alpha chains in a 1:1:1 ratio and showing the expected biphasic thermal melting profile. When the individual alpha chains were expressed, disulfide-bonded homotrimers and homodimers of the alpha chains were observed. When the cells were coinfected with the viruses for all three alpha chains, heterotrimers of alpha1(IX), alpha2(IX), and alpha3(IX) were detected in cell culture medium, and the other possible combinations were less prominent. When any two of the alpha chains were co-expressed, in addition to the homodimers and homotrimers, only alpha1(IX) and alpha3(IX) chains were disulfide-bonded. The results thus suggest that the most favored molecular species is an alpha1(IX)alpha2(IX)alpha3(IX) heterotrimer, but the chains are also able to form disulfide-bonded heterotrimers of alpha1(IX) and alpha3(IX) chains and (alpha1(IX))(3), (alpha2(IX))(3), and (alpha3(IX))(3) homotrimers.

Amino Acids↗
PubMed1999

In vivo microdialysis measures of extracellular serotonin in the rat hippocampus during sleep-wakefulness.

We investigated extracellular 5-hydroxytryptamine (5-HT) levels in rat hippocampus during different stages of the sleep-waking cycle using in vivo microdialysis. The extracellular 5-HT level was highest in active waking (AW) and, when compared to AW, 5-HT level was progressively lower in quiet waking (QW; 78%), quiet sleep (QS; 50%) and REM (which we termed active sleep (AS); 40%). Functional implications of AS related-decreased 5-HT in the hippocampus are discussed.

Animals↗
PubMed1999

Risk factors of otitis media with effusion during infancy.

UNLABELLED: Associations of possible risk factors with prevalence of otitis media with effusion (OME) were prospectively studied in a cohort of 250 infants, aged 0-2 years. In order to determine OME, otoscopy and tympanometry were performed at 3-monthly intervals beginning at term date. Eighteen epidemiologically relevant features were inventoried by means of standardized questionnaires. Multivariate analysis controlled for possible confounding factors. Prevalence of OME was most strongly associated with age (P-value < 0.001). Other factors significantly associated with the prevalence of OME (P-value < 0.05) were gestational age, birth weight, breastfeeding, day-care attendance, number of siblings, season, and parent-reported ear infection, hearing loss, mouth breathing and common cold. No significance was found for gender, date of birth, passive smoking, family history of otitis media, parental socio-economic status and histories of snoring and consultation of a physician. IN CONCLUSION: both intrinsic and extrinsic factors appear to play an important role in the prevalence of OME. Some of the risk factors appeared to be time-dependent.

Acoustic Impedance Tests↗