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J Engel

Publications and source records attributed to J Engel.

At least 235 records · Page 13Linked to original sources

Method of localization and implantation of the lumpectomy site for high dose rate brachytherapy after conservative surgery for T1 and T2 breast cancer.

PURPOSE: This article describes our technique of localization and implantation of the lumpectomy site of patients with T1 and T2 breast cancer. Our method was developed as part of our Phase I/II pilot study of high dose rate (HDR) brachytherapy alone after conservative surgery for early breast cancer. METHODS AND MATERIALS: In March 1992, we started a pilot study of HDR brachytherapy to the lumpectomy site as the sole radiotherapy after conservative surgery for clinical T1 or T2 invasive breast cancer. Initially, the protocol required intraoperative placement of the interstitial needles at the time of definitive surgery to the breast. The protocol was then generalized to allow the implantation of the lumpectomy site after definitive surgery to the breast, either at the time of subsequent axillary nodal dissection or postoperatively. To date, five patients have been implanted intraoperatively at the time of definitive breast surgery. Twelve patients were implanted after definitive breast surgery, with 7 patients being done at the time of axillary nodal dissection and 5 patients postoperatively. We devised a method of accurately localizing and implanting the lumpectomy site after definitive breast surgery. The method relies on the previous placement of surgical clips by the referring surgeon to mark the lumpectomy site. For each patient, a breast mold is made with radio-opaque angiocatheters taped onto the mold in the supero-inferior direction. A planning CT scan is then obtained through the lumpectomy site. The volume of the lumpectomy site, the number of implant planes necessary, and the orientation of the implants are then determined from the CT scan. The angiocatheters provide a reference grid on the CT films to locate the entry and exit points of the interstitial needles on the plastic mold. The entry and exit points for reference needles are then transferred onto the patient's skin enabling implantation of the lumpectomy site. Needle positions with respect to the lumpectomy site are then verified using simulator radiographs. RESULTS: Eight double plane implants and four single plane implants have been done using this method. Five implants were done using direct visualization. It has not been necessary to reorient the implant in any of the patients. If not for the presence of surgical clips, the size of the lumpectomy site cannot be separated from the surrounding normal breast tissue. CONCLUSION: This technique is an accurate way to localize the lumpectomy site for HDR brachytherapy.

Adult↗

Demonstration of non-linear detection in ELISA resulting in up to 1000-fold too high affinities of fibrinogen binding to integrin alpha IIb beta 3.

To clarify the question as to why different solid-phase assays yield different results in terms of interaction strength, we used fibrinogen binding to immobilized alpha IIb beta 3 integrin as a test system. A classical 'three step' enzyme-linked (ELISA), a 'two step' biotin enzyme-linked streptavidin and a 'one step' radioligand assay were compared under otherwise identical conditions. Only the last assay yielded binding constants comparable to earlier data by total internal reflection fluorescence microscopy while the other assays yielded apparent binding constants 5- to 1000-fold too high. These effects are explained by non-linearity of detection signals.

Enzyme-Linked Immunosorbent Assay↗

Outcome assessment for epilepsy surgery: the impact of measuring health-related quality of life.

Epilepsy surgery is an increasingly common treatment for intractable epilepsy; yet there is no clear consensus among experts on how to report epilepsy surgery outcome. Most published outcome reporting systems focus on seizure frequency and type but differ in how they define clinically distinct outcome categories. We used a reliable and valid measure of self-reported health-related quality of life (HRQOL), the Epilepsy Surgery Inventory (ESI)-55, as an external standard by which to evaluate seven previously published, seizure-based outcome classification systems. The ESI-55 was administered to 133 adults who had previously undergone surgery for intractable epilepsy, and results were linked to data on their seizure occurrence before and after surgery (over the year prior to their HRQOL reports). These 133 patients were classified according to each seizure-based outcome system, and variation in HRQOL across outcome groups was evaluated using analysis of variance. Results reveal noteworthy variation in the extent to which different systems reflect patients' HRQOL at follow-up. We modified existing systems to derive a seizure-based surgery outcome system that most closely reflects HRQOL when applied over the latest 1-year postoperative interval.

Adolescent↗

Transesterification reactions of parabens (alkyl 4-hydroxybenzoates) with polyols in aqueous solution.

Accelerated stability tests of aqueous solutions containing parabens and polyols were performed using concentrations similar to pharmaceutical and cosmetic formulations. Reaction products were detected in these solutions by HPLC and identified by chromatographic and spectroscopic means. Using xylitol and methylparaben as model reactants, three unknown peaks having the relation 1:2:4 were obtained together with the hydrolysis product 4-hydroxybenzoic acid. Diode array detection gave identical UV spectra for each peak with a maximum at 255 nm. The structures of the isomeric 1-, 2-, and 3-xylityl 4-hydroxybenzoic acid esters were proved by means of LC-MS, GC-MS, and NMR and correlated to the peaks in the HPLC chromatograms. The rate of the transesterification was shown to be highest in strongly alkaline medium (ph 10-11), whereas equilibration of the reaction was optimally balanced at pH 8-9. An increase of polyol concentration enhanced the formation of the esters. The reactivity of different substituted parabens was higher in the case of parabens with a short alkyl ester function. Similar reaction profiles were observed with C3-C6 polyols, but no transesterification took place when aldoses were used.

Chromatography, High Pressure Liquid↗

Type VI collagen beaded microfibrils from bovine cornea depolymerize at acidic pH, and depolymerization and polymerization are not influenced by hyaluronan.

Type VI collagen beaded microfibrils were extracted from bovine cornea or pig cartilage by limited collagenase digestion. Depolymerization of the microfibril, without strong denaturing reagents linke guanidinium hydrochloride or urea under mild acidic conditions, led to single tetramers and multiples of two to three. However, hyaluronidase digestion in accordance with a published method (Kielty et al. J. Cell Biol. 118:979-990, 1992) was unsuccessful in depolymerizing type VI collagen microfibrils. Also, repolymerization into microfibrils by incubation with hyaluronan was not observed. We further found no binding of native type VI collagen microfibrils to a hyaluronan-Sepharose column. Although a recombinant fragment comprising alpha 3(VI) domains N9-N2 showed apparent binding to the column, electron microscopy did not give any indication of binding of either type VI collagen or fragment N9-N2 to hyaluronan. The present findings suggest that the role of hyaluronan in polymerization of type VI collagen has been overestimated in previous work.

Animals↗

Temperature dependence of Ca2+ wave properties in cardiomyocytes: implications for the mechanism of autocatalytic Ca2+ release in wave propagation.

Digital imaging microscopy of fluo-3 fluorescence was used to study the velocity and shape of intracellular Ca2+ waves in isolated rat cardiomyocytes as a function of temperature. Decreasing the temperature from 37 to 17 degrees C reduced the longitudinal wave velocity by a factor of 1.8 and remarkably slowed the decay of [Ca2+]i in the trailing flank of a wave. Using image analysis, rise times, and half-maximum decay times of local Ca2+ transients, which characterize the processes of local Ca2+ release and removal, were determined as a function of temperature. Apparent activation energies for wave front propagation, local Ca2+ release, and local Ca2+ removal were derived from Arrhenius plots and amounted to -23, -28, and -46 kJ/mol, respectively. The high activation energy of Ca2+ removal, which arises from the activity of the sarcoplasmic reticulum (SR) Ca2+ ATPase, relative to those of longitudinal wave propagation and local Ca2+ release excludes the hypothetical mechanism of regenerative "spontaneous Ca2+ release," in which Ca2+ that has been taken up from the approaching wavefront triggers Ca2+ release at a luminal site of the SR. It is consistent, however, with the hypothesis that Ca2+ wave propagation is based on Ca(2+)-induced Ca2+ release where Ca2+ triggers release on the cytosolic face of the SR.

Aniline Compounds↗

Pressure dependence of collagen melting.

Calf skin collagen type I and interstitial collagen of the annelids Alvinella pompejana and Riftia pachyptila were thermally unfolded at pressures of 1 and 200 bar. The high pressure was near the habitat pressure of the annelids which live in deep sea hydrothermal vents. The transition temperature increased with pressure by only 1.4 +/- 1 degrees C for calf skin collagen, and no pressure effect was detectable for the annelid collagens. The value for calf skin collagen agrees with prediction based on published values of the transition volume and transition enthalpy. The triple helices of the interstitial collagens of the annelids, which have melting temperatures of 46 degrees C (Alivinella pompejana) and 29 degrees C (Riftia pachyptila), are not further stabilized by pressure.

Animals↗

Cloning and sequencing of mouse skeletal muscle alpha-dystroglycan.

alpha-Dystroglycan has attracted much interest due to its important function in linking laminin in the extracellular matrix and dystrophin in the muscle. The complete sequence of mouse skeletal muscle alpha-dystroglycan was produced and cloned by applying the reverse transcriptase-polymerase chain reaction approach to the total RNA extracted from the mouse myogenic cell line C2C12. The results demonstrate the usefulness of this approach and the high degree of conservation of alpha-dystroglycan between different species, and they provide the basis for additional work with the murine species.

Amino Acid Sequence↗

Development and applications of luteinizing hormone-releasing hormone antagonists in the treatment of infertility: an overview.

Luteinizing hormone-releasing hormone (LHRH) plays a crucial role in controlling the ovarian cycle in women. By modification of the molecular structure of this decapeptide, analogues were synthesized with agonistic or antagonistic effects on the gonadotrophic cells of the anterior pituitary gland. The agonists, after an initial stimulatory effect ('flare up'), lead to desensitization of the gonadotrophic cells and a reduction in the number of LHRH receptors on the cell membrane ('down-regulation'), while the antagonists produce an immediate effect by competitive blockade of the LHRH receptors. After administration of LHRH antagonists, the serum levels of FSH and LH decrease within hours. Nevertheless, the adenohypophysis maintains its responsiveness to an LHRH stimulus ('pituitary response') after pretreatment with an antagonist. This different pharmacological mechanism of LHRH antagonists makes possible new approaches to ovarian stimulation and to the therapy of sex steroid dependent diseases. The premature LH surge, the main cause of cancellation during induction of superovulation in assisted reproduction technology (ART) programmes, can be abolished by short term application of an LHRH antagonist associated with a reduced human menopausal gonadotrophin (HMG) requirement for ovarian stimulation. A future approach to ART might be based on the combination of pretreatment with an LHRH antagonist and ovulation induction by native LHRH or an agonist. The severe side effects encountered with early LHRH antagonists, such as anaphylactoid reactions due to histamine release, are almost completely eliminated in modern antagonists, especially Cetrorelix which is presently used clinically in controlled phase II clinical studies.

Adult↗

Characterization of Pseudomonas aeruginosa-induced MDCK cell injury: glycosylation-defective host cells are resistant to bacterial killing.

As a model for bacterium-induced epithelial cell injury, we have studied the interaction of Pseudomonas aeruginosa with polarized Madin-Darby canine kidney (MDCK) cells grown on filters. Following an initial period of bacterial adhesion, foci of injured host cells, which consisted of a central region of cell debris, surrounded by cells that were permeable and apparently necrotic, were formed. Host cell death was quantified by measuring the increased permeability of the monolayer to the macromolecular tracer [14C]inulin. Using this MDCK model system, we have identified bacterial and host cell factors necessary for the host cell damage. The ability of P. aeruginosa to cause MDCK cell damage was independent of elastase or exotoxin A production. In contrast, bacteria with a mutation in the regulatory locus exsA (which are deficient in exoenzyme S production) neither bound to nor caused host cell injury. MDCK cells with defects in cell surface glycosylation were resistant to cell injury, indicating that bacteria may require host cell glycolipids and/or glycoproteins as points of adhesion to cause subsequent host cell injury.

Animals↗

Diet restriction in rhesus monkeys lowers fasting and glucose-stimulated glucoregulatory end points.

Male rhesus monkeys (Macaca mulatta) of different age groups representing the species life span were fed ad libitum or a 30% reduced calorie diet over a 7-yr period. During the first 2-3 yr of this longitudinal study, glucose and insulin levels were not altered by diet restriction (DR). However, reductions in fasting blood glucose became apparent in DR animals after 3-4 yr. At the end of the 6th yr of study, glycated hemoglobin was measured, and intravenous glucose tolerance tests (IVGTTs) were conducted. Maximum glucose levels reached during IVGTTs increased with age but were lower in DR animals compared with controls. Several measures of the insulin response (baseline, maximum, and integrated areas under curve) increased with age and were lower in DR monkeys. With the exception of glycated hemoglobin, which was not different in monkeys subjected to DR, these findings confirm previous studies in rodents demonstrating that DR alters glucose metabolism and may be related to the antiaging action of this intervention.

Aging↗

Synthesis and antitumor activity of two ifosfamide analogs with a five-membered ring.

Two ifosfamide (CAS 3778-73-2) analogs with a five-membered ring, i.e. the oxazaphospholidine derivatives 6 and 7, were synthesized and their cytotoxic activity in vitro, acute toxicity and antitumor activity in vivo determined in comparison with the oxazaphorinane ifosfamide 1. The observed low biological activity gives evidence that both, the six-membered oxazaphosphorinane ring and the two N-2-chloroethyl-side chains are necessary for the generation of the ultimate alkylator, i.e. the ifosfamide mustard 5.

Animals↗