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Biomedical subjects

J Engel

Publications and source records attributed to J Engel.

At least 343 records · Page 19Linked to original sources
PubMed1991

Tumor inhibiting [1,2-bis(difluorophenyl)ethylenediamine]dichloroplatinum (II) complexes, I: Synthesis.

The synthesis of the diastereomeric 1,2-bis(2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5-difluorophenyl)ethylenediamine (meso, D/L 8-13) from meso 1,2-bis(2-hydroxyphenyl)ethylenediamine and the respective difluorobenzaldehyde by a diaza-Cope-rearrangement and their conversion into the [1,2-bis(2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5-difluorophenyl)ethylenediamine]dihaloplatinum(II)- complexes (meso, D/L 8-13 PtCl2; meso D/L 9- and 11-PtI2) with K2PtHal4 (Hal = Cl, I) is described. From the diiodoplatinum(II)-complexes (meso D/L 9- and 11-PtI2) the better water soluble diaqua[1,2-bis(2,4- and 2,6-difluorophenyl)ethylenediamine]platinum(II) sulfates (meso, D/L 9- and 11-PtSO4) are obtained by reaction with Ag2SO4.

Antineoplastic Agents↗
PubMed1991

Recombinant nidogen consists of three globular domains and mediates binding of laminin to collagen type IV.

Recombinant mouse nidogen and two fragments were produced in mammalian cells and purified from culture medium without resorting to denaturing conditions. The truncated products were fragments Nd-I (positions 1-905) comprising the N-terminal globule and rod-like domain and Nd-II corresponding mainly to the C-terminal globule (position 906-1217). Recombinant nidogen was indistinguishable from authentic nidogen obtained by guanidine dissociation from tumor tissue with respect to size, N-terminal sequence, CD spectra and immunochemical properties. They differed in protease stability and shape indicating that the N-terminal domain of the more native, recombinant protein consists of two globules connected by a flexible segment. This established a new model for the shape of nidogen consisting of three globes of variable mass (31-56 kDa) connected by either a rod-like or a thin segment. Recombinant nidogen formed stable complexes (Kd less than or equal to 1 nM) with laminin and collagen IV in binding assays with soluble and immobilized ligands and as shown by electron microscopy. Inhibition assays demonstrated different binding sites on nidogen for both ligands with different specificities. This was confirmed in studies with fragment Nd-I binding to collagen IV and fragment Nd-II binding to laminin fragment P1. In addition, recombinant nidogen but not Nd-I was able to bridge between laminin or P1 and collagen IV. Formation of such ternary complexes implicates a similar role for nidogen in the supramolecular organization of basement membranes.

Animals↗
PubMed1991

Functional connections in the human temporal lobe. II. Evidence for a loss of functional linkage between contralateral limbic structures.

In a previous investigation of functional limbic pathways in the human mesial temporal lobe, we found evidence for strong connections between ipsilateral mesial temporal structures, but none for contralateral functional connections (Wilson et al. 1990). In the present study, we focused specifically upon the question of functional commissural linkages between these structures by systematic stimulation of a total of 390 electrode placements in 74 epileptic patients with temporal lobe depth electrodes implanted for surgical diagnosis. Eight standard electrode placement regions were targeted: amygdala, entorhinal cortex, anterior, middle and posterior hippocampus, subicular cortex, middle parahippocampal gyrus, and posterior parahippocampal gyrus. Three to six electrodes were implanted bilaterally in each patient, and each electrode was individually stimulated while recording from all the other sites. Out of the 390 electrodes stimulated, 78% were effective in evoking clear responses in adjacent ipsilateral structures, and 75% of 581 ipsilateral recording sites were responsive to stimulation. Only one of the stimulated electrode sites was effective in evoking responses in contralateral recording sites, and only two of 511 contralateral recording sites were responsive to that stimulation. The effective stimulation site was in presubicular cortex, and the responsive contralateral recording sites were in entorhinal and presubicular cortices. Response to this stimulation site was intermittent and variable in latency. The relative ease of obtaining functional verification of significant ipsilateral anatomical pathways in the human limbic system, and the sharply contrasting difficulty of functionally activating commissural pathways to contralateral limbic sites are discussed in the context of decreases in hippocampal contribution to commissural pathways in the primate brain compared to sub-primate mammals, and the significance of this change to normal limbic system function as well as to mechanisms of seizure spread in epilepsy.

Amygdala↗
PubMed1991

Domains in proteins and proteoglycans of the extracellular matrix with functions in assembly and cellular activities.

Most proteins of the extracellular matrix (ECM), such as the glycoproteins, collagens and proteoglycans, consist of many structurally autonomous domains that are often functionally distinct. Consequently these proteins are designated as mosaic proteins. Related domains are often found in several different ECM proteins. Domains which are of importance for assembly have been identified by fragmentation and other approaches. Triple-stranded coiled-coil domains in laminin and probably also in tenascin and thrombospondin are responsible for chain selection, a process which may be important for the formation of tissue specific isoforms. Globular domains at the C-terminus of collagenous domains are essential for the registration of the three chains and triple-helix formation. Fibrillar assemblies of these triple helices with constituent globular domains serve important assembly functions in many collagens including collagens IV and VI. Many other domains with more specialized functions in assembly have been identified in laminin, fibronectin and other ECM proteins. Cys-rich domains with either distant or close homology with epidermal growth factor are repeated manifold in rod-like regions of a number of ECM proteins including laminin, tenascin and thrombospondin. They may serve as spacer elements but as suggested for laminin some domains of this type may also function as signals for cellular growth and differentiation. Another important cellular function common to many ECM proteins is cell attachment. Several cell attachment sites have been localized in structurally unrelated domains of the same or of different ECM proteins.

Cell Adhesion↗
PubMed1991

Common structural motifs in proteins of the extracellular matrix.

Proteins of the extracellular matrix are composed of many structurally and often functionally different autonomous domains which frequently occur as modular units in several different extracellular matrix proteins, but also in proteins of different origin. Some domains serve related assembly functions in different proteins but for domains involved in cell attachment and other cellular activities only a few generalizations are possible.

Animals↗
PubMed1991

Factors influencing elbow arthrolysis.

Over the period 1982 to 1988, 31 consecutive patients at the Hand Surgery Unit of the Sheba Medical Centre were subjected to elbow joint arthrolysis to treat restriction of range of motion solely due to trauma. This retrospective study aims to evaluate the relative influence of the followings factors on functional outcome: sex, age, type of original injury and initial management, presence of para-articular ossification, delay between injury and arthrolysis, and the use of manipulation and a continuous passive motion device (CPM) following surgery. The range of motion was recorded prior to arthrolysis and after operation (excluding one patient who subsequently underwent arthrodesis for intractable pain). Follow-up averaged 15.3 months (+/- 5.4). In the 24 patients with extension deficit (greater than 20 degrees), the mean improvement was of 26.9 degrees (greater than 23.1 degrees); in the 21 patients with flexion deficit the mean improvement was of 21.2 degrees (greater than 18 degrees). The mean improvement for total range of motion in the series overall was of 35.2 degrees (+/- 23.8 degrees). 90% showed an improvement of at least 10 degrees and 30% attained normal ROM. All of these improvements in range were statistically highly significant (p less than 0.0001). None of the variables had predictive value with regard to improvement of flexion. With regard to improvement in extension, the only variable of value was the use of a continuous passive motion device following surgery; those patients subjected to CPM showed a mean improvement of 32.6 degrees (+/- 19.0 degrees), while those without averaged 12.8 degrees (+/- 27.5 degrees) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

PET scanning in partial epilepsy.

Many biologically active tracers are available for positron emission tomography (PET) investigations, but most studies of epilepsy have utilized 18F-fluorodeoxyglucose (FDG) to measure local cerebral metabolic rate for glucose. Over 70% of patients with medically refractory partial seizures demonstrate an interictal zone of hypometabolism corresponding to the epileptogenic region. This metabolic defect commonly involves the temporal lobe in patients with complex partial seizures of mesial temporal origin, and is encountered less consistently with seizures of extratemporal neocortical origin. Although false localization is less likely with FDG-PET than with EEG, the hypometabolic zone merely reflects a focal functional deficit and its epileptogenicity must still be demonstrated electrophysiologically. When hemispherectomy or large multilobar resections are planned in small children, FDG-PET also provides useful supporting evidence that the contralateral hemisphere is functioning normally. It is difficult to obtain FDG-PET scans and to interpret results during spontaneous partial seizures. Ictal scans can be more easily obtained with single photon emission computed tomography (SPECT), which may provide information for planning surgical resections.

Electroencephalography↗
PubMed1991

A process for developing a curriculum in ethics and human values.

This article describes the process and results of the deliberations of the group of authors at the 1989 spring meeting of the Northeast Group for Educational Affairs. The participants worked under the premise that someone had given an unlimited amount of money to fund a new medical school. They had to select and define what the educational goals would be and produce a plan to help students reach these goals. There had to be an evaluation process that documented progress toward the stated goals. This paper describes the ethics and human values curriculum, which should be of interest to cancer educators. The knowledge, skills, values, and attitudes are defined and the four-year process of implementing the teaching is described. This curriculum-planning process is applicable to any aspect of cancer education--first defining the outcome, then the evaluation process, and finally, how to get to that outcome.

Curriculum↗
PubMed1991

Mini-collagens in hydra nematocytes.

We have isolated and characterized four collagen-related c-DNA clones (N-COL 1, N-COL 2, N-COL 3, N-COL 4) that are highly expressed in developing nematocytes in hydra. All four c-DNAs as well as their corresponding transcripts are small in size (600-1,000 bp). The deduced amino acid sequences show that they contain a central region consisting of 14 to 16 Gly-X-Y triplets. This region is flanked amino-terminal by a stretch of 14-23 proline residues and carboxy-terminal by a stretch of 6-9 prolines. At the NH2- and COOH-termini are repeated patterns of cysteine residues that are highly conserved between the molecules. A model is proposed which consists of a central stable collagen triple helix of 12-14 nm length from which three 9-22 nm long polyproline II type helices emerge at both ends. Disulfide linkage between cysteine-rich segments in these helices could lead to the formation of oligomeric network structures. Electrophoretic characterization of nematocyst extracts allows resolution of small proline-rich polypeptides that correspond in size to the cloned sequences.

Amino Acid Sequence↗
PubMed1991

Tissue expansion in reconstruction of postburn contracture of the first web space of the hand.

The successful release of severe contracture of the first web space depends on addition of a sufficient amount of skin. Because local skin is limited, skin grafts tend to contract, and free and pedicle flaps are bulky, further procedures are often obligatory. Expansion of the tissues of the dorsum of the hand offers an effective and relatively simple approach to generate the excess skin needed. We present a patient in whom an inflatable silicone implant was used to correct recurrent first web space contracture after burns.

Adolescent↗
PubMed1991

On the interaction between chromaffin granule membranes and intragranular vesicles--theory and analysis of freeze-fracture micrographs.

We present a model for the calculation of intragranular vesicle adhesion energy in a two-vesicle system consisting of an external secretory vesicle (chromaffin granule) and an intragranular vesicle (IGV) that adheres from the inside to the granule membrane. The geometrical parameters characterizing the granule-IGV systems were derived from freeze-fracture electron micrographs. Adhesion is brought about by incubation of the granules in hyperosmolar sucrose solutions. It is accompanied by a deformation of the granule because the intragranular vesicle bulges it outwards, and by segregation of intramembraneous particles from the adherent part of the granule membrane. Adhesion prevents the deformed granules from osmotic reexpansion and, therefore, causes hyperosmotic relaxation lysis. We estimated specific adhesion energy at -3 erg/cm2, a value which is 10 - 1000 times larger than the energy of van der Waals interaction between membranes. This large interaction energy probably results from changes of the granule core induced by dehydration. A minimization of the interface between the granule core and adjacent membranes could exclude intragranular vesicles from the core and squeeze them towards the granule membrane. This might induce a new kind of interaction between both membranes, which is irreversible and causes lysis upon osmotic relaxation.

Adhesiveness↗
PubMed1991

[Synthesis, biotransformation and pharmacodynamics of a new theophylline derivative].

7-[(RS)2-((S)-1-Methyl-2-phenyl-ethylamino)propyl]-theophylline (3) was not described until now. This fenetylline analogue is available by reaction of 7 with an excess of 2 at 150 degrees C. If 2 reacts with 4, an E2-elimination overwhelms SN-nucleophilic displacement yielding compound 5. In vivo studies with male White-Wistar rats, comparing biotransformation of 3 and 1, demonstrate, that the amount of 2 is decreased from 4.7% of (RS)-2 to 1%, probably due to steric hindrance of the attacking monooxygenases by the methyl group at C-11 of 3. Pharmacodynamic studies of 3, tested with mice, gave similar results to those obtained with 1.

Animals↗
PubMed1991

Neurobiological evidence for epilepsy-induced interictal disturbances.

It is not in the best interest of persons with epilepsy to deny the possibility that seizures could cause enduring behavioral disturbances. Rather, it is essential to pursue clinical and animal investigations in order to identify any such changes that might occur and to elucidate their mechanisms. Many testable hypotheses can be developed from existing evidence. Antiepileptic medication may produce interictal behavioral disturbances in patients with epilepsy by indirect mechanisms. Some aberrant behaviors could be due to medication-induced systemic disorders, neuroendocrine dysfunction, or REM deficit, whereas depression following successful treatment with drugs, as well as with surgery, may be related more specifically to cessation of seizures. The underlying neuropathological process also induces neurological and mental deficits, but it is not always possible to differentiate those behavioral disturbances due to destructive effects of the lesion from those due to recurrent epileptic seizures. Behavioral disturbances are associated more frequently with epileptogenic lesions in limbic structures than with those elsewhere in the brain, but a relationship between hemispheric lateralization of the epileptogenic lesion and specific interictal behavioral symptoms remains controversial. When considering the effects of seizures per se on interictal behavior, it is important to realize that some "interictal" behavioral disturbances may actually be ictal events. Prolonged affective, autonomic, and psychic disturbances can occur in clear consciousness with unilateral limbic seizures that are not associated with scalp EEG changes. When epilepsy is acquired as a result of cerebral damage, the epileptogenic process takes time to develop before spontaneous seizures appear. It is more reasonable to assume that this progressive process continues than to postulate that it stops completely at the time the first seizure occurs. Epilepsy-induced protective homeostatic mechanisms that act to terminate ictal events, prevent ictal spread, and maintain the interictal state may also disrupt interictal function. Furthermore, seizures could indirectly influence interictal behavior as a result of their effects on neuroendocrine function and sleep. Because of confounding biological factors, it is difficult to document the association of any epilepsy disorder, by itself, with progressive behavioral disturbances in humans. Secondary epileptogenesis, protective homeostatic mechanisms, and epilepsy-induced disturbances in development can be readily demonstrated, however, in experimental animal models. In experimental animals, endogenous opoids are released during seizures and mediate some postictal behaviors. A physiological dependency on high levels of endogenous opioids released during seizures could produce depression as a withdrawal symptom interictally or when seizures no longer occur as a result of successful therapy. Experimental animal models of depression exist to test hypotheses concerning pro- and antidepressant effects of epileptogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Single amino acid substitutions in one Ca2+ binding site of uvomorulin abolish the adhesive function.

We show that a synthetic peptide corresponding to the sequence of one putative Ca2+ binding motif of the cell adhesion molecule uvomorulin is able to complex Ca2+. This function is abolished if the first Asp in the peptide is replaced by Lys. Accordingly, we expressed in L cells mutant uvomorulin with a replacement of Asp to Lys or Ala. Mutant protein was resistant to Ca2+/trypsin under mild conditions but became susceptible at or near the site of replacement at higher concentrations, leaving the remaining Ca2+ binding domains protected. Remarkably, in cell aggregation assays both mutant uvomorulins failed to mediate cell adhesiveness, demonstrating that a single amino acid substitution in one Ca2+ binding site inactivates the adhesive function.

Amino Acid Sequence↗