Biomedical subjects

L Bischoff

Publications and source records attributed to L Bischoff.

12 recordsLinked to original sources

PubMed2000

Binding properties of a highly potent and selective iodinated aminopeptidase N inhibitor appropriate for radioautography.

Aminopeptidase N (APN) is a zinc metallopeptidase involved in the inactivation of biologically active peptides. The knowledge of its precise distribution is crucial to investigate its physiological role. This requires the use of appropriate probes such as the recently developed highly potent and selective radiolabeled APN inhibitor 2(S)-benzyl-3-[hydroxy(1'(R)-aminoethyl)phosphinyl]propanoyl-L-3-[ (12 5)I]iodotyrosine ([(125)I]RB 129). Its binding properties were investigated using rat brain homogenates (K(d)=3.4 nM) or APN expressed in COS-7 cells (K(d)=0.9 nM). The specific binding was 95% at [K(d)], and preliminary autoradiography in intestine is promising. The decreased affinity of [(125)I]RB 129 (=10(-6) M) for the E(350)D APN mutant, supports the critical role of E(350) in the amino-exopeptidase action of APN.

Amino Acid Substitution↗

PubMed1999

Investigation of subsite preferences in aminopeptidase A (EC 3.4.11.7) led to the design of the first highly potent and selective inhibitors of this enzyme.

The study of the physiological roles of the membrane-bound zinc-aminopeptidase A (glutamyl aminopeptidase, EC 3.4.11.7) needs the design of efficient and selective inhibitors of this enzyme. An acute exploration of aminopeptidase A active site was performed by a combinatorial approach using (3-amino-2-mercapto-acyl)dipeptides able to fit its S(1), S(1)', and S(2)' subsites. This analysis confirmed that the S(1) subsite is optimally blocked by a glutamate or isosteric residues and demonstrated that the S(1)' subsite is hydrophobic whereas the S(2)' subsite recognizes preferentially negatively charged residues derived from aspartic acid. The optimization of these structural parameters led to the synthesis of nanomolar and subnanomolar inhibitors of aminopeptidase A such as H(3)N(+)CH(CH(2)CH(2)SO(3)(-))CH(SH)CO-Ile-(3-COOH)Pro that exhibits a K(i) of 0.87 nM. The best compounds were synthesized by a stereochemically controlled route. These first described highly potent inhibitors could allow studies about the role of physiological substrates of APA such as angiotensin II and cholecystokinin CCK(8) in the central nervous system.

Aminopeptidases↗

PubMed1998

Inhibition of vasopressinergic neurons by central injection of a specific aminopeptidase A inhibitor.

The brain angiotensin (Ang) system plays an important role in the central control of vasopressin release. Using EC33, a selective aminopeptidase A inhibitor which blocks the metabolism of Ang II in Ang III, we previously reported that vasopressin release was under the control of Ang III and not Ang II. To determine accurately the action of EC33, the effects of intracerebroventricular injection of Ang peptides or EC33 on extracellular unit activity of vasopressinergic neurons in the supraoptic nucleus of urethane-anaesthetized rats were examined. Angiotensin II (15-30 ng) or Ang III (15 ng) increased the firing rate of all neurons tested. Conversely, EC33 (10 microg) reduced or completely abolished (30-60 microg) the basal firing rate for 4-6 min in all eight neurons tested. EC33 (30 microg) also inhibited the activity induced by 30 ng Ang II. It was concluded that the observed activity of Ang II required its conversion to Ang III and that endogenous Ang III may exert a tonic control on the basal firing level of vasopressinergic neurons.

Aminopeptidases↗

PubMed1998

Exacerbated pain in cervical radiculopathy at axial rotation, flexion, extension, and coupled motions of the cervical spine: evaluation by kinematic magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The authors evaluate the functional changes in patients with cervical radiculopathy and increasing symptoms after provocative maneuvers at flexion, extension, axial rotation, and coupled motions of the cervical spine. METHODS: Twenty-one patients with cervical disc herniation (n = 17) or cervical spondylosis (n = 4) in whom symptoms were elicited at flexion, extension, axial rotation, and coupled motions of the cervical spine were studied. The patients were examined inside a positioning device by using a circular surface coil for signal reception. At neutral position (0 degrees) and at provocative positions sagittal T2-weighted turbo spin-echo, axial T2-weighted two-dimensional flash sequence, sagittal three-dimensional (3D) fast imaging with steady state precision sequence and coronal 3D double-echo-in-the-steady-state sequences were obtained. The 3D sequences were reformatted in the axial and oblique coronal planes perpendicular to the exiting nerve roots. The images were evaluated for the size of disc herniations, the foraminal size and cervical cord rotation or displacement at provocative position compared with neutral position (0 degrees). RESULTS: Compared with neutral position (0 degrees), change in size of disc herniation was not found in any (0%) of the provocative positions. In five (24%) patients cervical cord rotation or displacement was noted at axial rotation. The foraminal size increased at flexion, axial rotation to the opposite side of pain and flexion combined with axial rotation to the opposite side of the pain. The foraminal size decreased at extension combined with axial rotation to the side of the pain. A decrease or no change in foraminal size was observed at either extension or axial rotation to the side of the pain. CONCLUSIONS: In patients with cervical disc herniation or cervical spondylosis, exacerbated pain at defined provocative maneuvers is related more to changes in the foraminal size and to nerve root motion with, in some cases, cervical cord rotation or displacement than to changes in the size of herniated discs.

Adult↗

PubMed1997

[Comparison of T2-weighted turbo spin-echo and ultrafast HASTE sequence in the diagnosis of cervical myelopathies and spinal stenoses and static and kinematic MRT of the spine].

PURPOSE: The purpose of this study was to compare HASTE-sequence with T2-weighted TSE-sequence in the detection of cervical myelopathy and cervical spinal stenosis in kinematic MRI. METHODS: 24 patients with degenerative disease of the cervical spine were studied. Images were evaluated according to the following criteria: artifacts, delineation of the vertebra, disks and degenerative changes, grade of spinal stenosis (grade 0-3) and evaluation of the cervical spinal cord. RESULTS: Due to image blurring and artifacts, evaluation and delineation of the cervical spine was possible in all cases in the T2-weighted TSE-sequence, but only in 23 of 24 patients using HASTE-sequence. Differentiation between osteophytes and disks was obtained in most cases (23/24) in the T2-weighted TSE-sequence but none in the HASTE-sequence. Cervical myelopathy was observed in 4 patients in T2-weighted TSE images but only in two cases using HASTE-sequence. Compared to T2-weighted TSE-sequence spinal canal stenosis was underestimated using HASTE-sequence. CONCLUSION: T2-TSE-sequence is superior to HASTE-sequence in the delineation of anatomical structures of the cervical spine, the grading of cervical spinal stenosis and the evaluation of cervical myelopathy.

Adult↗

PubMed1987

Searching for parasites in stool: once is usually enough.

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Canada↗

PubMed1985

Cryptosporidiosis: a cause of summer diarrhea in children.

Recent studies have suggested that some outbreaks of diarrhea in children may be caused by Cryptosporidium, a parasite associated with gastrointestinal and respiratory tract infection in animals. In a study of 7300 British Columbia patients with diarrhea, cryptosporidial oocysts were found in the stool samples of 46 (0.63%). It appears that the occurrence of cryptosporidiosis is related to three factors: the patient's age, the time of year and the geographic location.

Adolescent↗

PubMed1971