Chemical shift differences between free and Fab-bound peptide correlate with a two-stage selection of peptide sequences from a random phage display library to delineate critical and non-critical residues for antibody recognition

Epitope libraries provide a method to identify peptide ligands for antibodies, receptors or other binding proteins. As such, they provide a powerful tool to rapidly identify lead ligands in the drug discovery process. In an attempt to correlate structural information with the results from peptide screening, we have used NMR spectroscopy of peptide/antibody complexes to demonstrate that core residues identified through a two-stage selection process undergo a larger structural change upon binding antibody than do positions in the peptide amenable to a variety of side chains. The model system used was the M2 monoclonal antibody/Flag? octapeptide epitope system. We have analyzed two peptides: Ac-Asp-Tyr-Lys-Leu-Gly-Asp-Asp-Leu-NH₂ (peptide l), which contains several non-core positions randomized, and Ac-Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Leu-NH₂ (peptide 2), which closely corresponds to the original Flag? sequence. Enrichment of the peptides with ¹⁵N facilitated the investigation by permitting spectral editing of the peptide resonances in the presence of antibody. For peptide 1 the absolute shifts for the free vs. Fab-bound peptide were found to be largest for the amide groups of Asp-1 and Asp-6, in agreement with classification of these residues as critical by the phage display library selection process. For peptide 2 the largest absolute shifts were observed for Asp-1 and Asp-4, with the other aspartic acid residues also showing significant but smaller changes. © Munksgaard 1995.     

Megestrol acetate therapy for anorexia and weight loss in children with malignant solid tumours

Background : Malnutrition is very frequent in childhood cancer. Its main cause is inadequate intake for energy demands owing to lack of appetite. Megestrol acetate is a synthetic progestin that has been used for reversing anorexia in adult cancer.
Objectives : To assess megestrol acetate efficacy and side-effects in treating anorexia in childhood cancer.
Methods : Thirty-five children with solid tumours were receiving antitumour therapy. Nutritional assessment was by anthropometry. Megestrol acetate efficacy was assessed by evaluating grade of appetite, energy intake and well-being. Side-effects were evaluated by means of clinical history, physical examination, lipid profile, coagulation tests and cortisol rhythm.
Results : When compared to baseline all the anthropometric measurements increased ( P <0.05) from the first month of megestrol acetate therapy, as well as appetite and energy intake. No significant side-effects were found.
Conclusion : Megestrol acetate therapy is a powerful appetite stimulant which led to weight gain, composed of both fat mass and fat-free mass. Megestrol acetate is well tolerated, with few and mild side-effects. If megestrol acetate therapy is started at the onset of anorexia, the use of more expensive, invasive and complicated techniques of nutritional support may be avoided.     

Effects of baclofen and phaclofen on receptive field properties of rat whisker barrel neurons

Extracellular single-unit recordings were made in somatosensory cortical barrels of fentanyl-sedated rats. Whiskers were deflected singly or in paired combinations. lontophoretically-applied (−)-baclofen disproportionately reduced weak responses, and phaclofen disproportionately increased them, resulting in more tightly focused or more broadly focused receptive fields, respectively. Both drugs had only minor effects on surround inhibition. In light of previous findings, we conclude that GABA_A and GABA_B mechanisms both act to enhance spatial contrast, but that the former plays a much greater role in enhancing temporal resolution.     

Sondengesteuerte Choriozottenbiopsietechnik — eine prospektive randomisierte Studie

Ohne Zusammenfassung     

Clusterlike Headache as a First Sign of Brain Metastases of Lung Cancer

We report on a patient with clusterlike headache and multiple brain metastases of lung cancer. Initially, cluster headache was suggested clinically by characteristic symptoms without any focal central nervous system signs. However, magnetic resonance imaging demonstrated multiple brain metastases. It is possible that tumor necrosis factor may have played a role in initiating the clusterlike headache.     

High-dose intravenous immunoglobulin therapy improved muscle strength in a patient with multifocal motor neuropathy and antibodies against the glycolipid LK1

We report improvement in muscle strength in a patient with multifocal motor neuropathy (MMN) when given high-dose intravenous immunoglobin (i.v.-Ig) treatment. The patient had asymmetrical limb weakness, atrophy and absent or weak reflexes, but no sensory disturbances. Neurography showed multiple conduction blocks in peripheral motor nerves but no sensory nerve abnormalities. Serum and anti-GM1 antibodies were not found, however, the patient had serum antibodies against the glycolipid LK1, an epitope found both in glycolipid and also in some glycoproteins in peripheral nerve myelin. Muscle strength improved 5 days after i.v.-Ig therapy, and lasted about 10 weeks. Repeated courses of treatment resulted in similar improvement. This is, to our knowledge, the first patient reported with MMN found to have antibodies against the glycolipid LK1.     

The role of microsomal oxidation processes in the development of haloperidol tolerance during melatonin administration and epiphysectomy in rats

A pineal hormone melatonin (1 mg/kg, 24 days) facilitated the formation of tolerance to haloperidol and eliminated the changes produced by it in the processes of microsomal oxidation in rats. Pinealectomy yielded the opposite result. After pinealectomy the normalizing effect of the hormone on the condition of the liver monoxygenase system and the effects of haloperidol weakened.