Analysis of the H-2Kbm8 mutant: correlation of structure with function.

The gene for H-2K class I major histocompatibility antigen on the bm8 variant was cloned and the DNA sequence compared with the parental gene. Sequence analysis demonstrated that seven nucleotides were changed with respect to the parental gene sequence spanning 24 nucleotides. These changes represent an alteration of four amino acids from the parent protein. As this mutation occurred in a single generation, a potential donor gene for such a complex mutation was suggested and identified. The Q4 gene class I-like molecule has a stretch of 95 nucleotides of identity in the region of the bm8 mutation. Genomic Southern analysis of the mutant and parental DNA with a gene-specific oligonucleotide demonstrated that the potential donor gene Q4 is a likely candidate sequence for such an event. The amino acid alterations for the H-2Kbm8 mutation are discussed in consideration of hte three-dimensional structure of the characterized human class I glycoprotein.     

Reactivation of the alpha 1-fetoprotein synthesis in systemic lupus erythematosus

Serum concentrations of AFP have been determined in patients suffering from systemic lupus erythematosus (SLE) or other "collagenoses" using fluorescence ELISA adapted to the chamber analytical technique. 20% of the SLE patients showed elevated AFP levels (range 30-233 ng/ml), some of them repeatedly. Only 2 of the 14 patients without SLE had AFP levels above 30 ng/ml (37 resp. 40 ng/ml). In SLE sera there was a significant correlation of raised AFP to higher anti-dsDNA antibody concentrations (Mann-Whitney U-test: p = 0.042). The mean dosage of azathioprin and prednisone in patients with SLE did not significantly differ from the non-SLE group. We discuss the possible reactivation of AFP synthesis on account of SLE itself.     

External trauma to the larynx: classification, diagnosis, therapy

In contrast to internal trauma to the larynx caused by endolaryngeal procedures, trauma to the larynx caused by external forces is relatively rare. Nevertheless, the great variety of these external traumata warrants a thorough diagnosis and understanding of each case as well as a standardized and accepted method for classifying these injuries. These preconditions will facilitate successful therapy. At our three institutions cases of external trauma to the larynx, including the mechanisms of trauma, were reviewed and analyzed. Cases were classified according to the mechanisms and the sequelae of trauma. The three major categories were (a) external trauma due to the impact of blunt objects, (b) trauma after tearing of the neck and the larynx longitudinally, and (c) external trauma caused by sharp objects and gunshots. In the great majority of cases external trauma to the larynx was caused by blunt pressure and was most often due to strangulation in the course of (attempted) suicide or homicide. In a smaller number of cases sharp instruments caused external traumata. In patients surviving the immediate trauma a meticulous laryngological assessment is necessary. In addition to indirect laryngoscopy, we consider microlaryngoscopy as being indicated for investigating the soft tissues of the endolarynx. The status of the laryngeal skeleton can be determined more precisely via high-resolution computed tomography and ultrasound. Early diagnosis and appropriate therapy have a significant impact on the patient’s condition later, especially as regards scar formation, ease of breathing, and voice quality. Received: 16 August 1999 / Accepted: 19 May 2000     

Discrimination learning of amplitude modulated tones in Mongolian gerbils

Discrimination learning of 100% sinusoidal amplitude modulated tones (AM) was investigated in adult Mongolian gerbils using a footshock motivated shuttle box avoidance go/no go paradigm. AM stimuli to be discriminated had identical carrier frequency (2 kHz) but differed in modulation frequency (fm) by one octave. Six groups of gerbils were trained to discriminate AM-pairs with fm ranging from 10 to 640 Hz. Learning proceeded faster and discrimination performance was slightly better for low fm, up to 80 Hz, than for high fm, above 80 Hz. These results may be related to cortical AM encoding (Schulze, H. and Langner, G., J. Comp. Physiol. A, 181 (1997) 651-663), which is temporal for low fm (synchrony code) and spatial for high fm (rate-place code). This may implicate different neuronal learning strategies or distinct behavioral meanings influencing the discrimination training.     

Effects of the propofol combination anesthesia on the intrinsic blood-clotting system

Fat emulsions can cause changes in blood-clotting and fibrinolysis. The aim of this study was to examine the relation between the use of the short-acting hypnotic propofol and alteration of the blood clotting system. In a double-blind randomized study, 36 patients with an aortocoronary bypass operation were given either midazolam/fentanyl or propofol/alfentanil. Eleven blood samples were taken at fixed times pre-, intra- and postoperatively to determine changes caused by the anesthetic agents on the hemostaseologic parameters during the whole operation. Perioperative blood pressures of both groups were measured at seven fixed points. From the beginning of the extracorporeal circulation (ECC) to the end of the operation, the measured values of the factor XIIa- and kallikrein-like activity in the propofol group were significantly higher than those of the midazolam group. Also the values of the kallikrein inhibition capacity and the indicators of fibrinolysis (t-PA and D-dimers) suggest a stronger activation of the contact phase at the start of the recirculation and as a result of it a stronger fibrinolysis within the propofol group. Besides, the hypotensive side-effect in the propofol group was evident in contrast to the midazolam group. With this investigation, a correlation between the application of propofol/alfentanil, contact phase activation with activation of the kallikrein-kinin-bradykinin system and the observed hypotension can be set up.     

A new principle of injectable depot contraceptives. I Drug selection and studies in monkeys.

The aim of the investigations was to develop a long-acting depot contraceptive on the basis of norethisterone or levonorgestrel. Disappointing results with levonorgestrel nonanoate and levonorgestrel undecylate showed that elongation of the fatty acid, esterified with the steroid, decreased the bioavailability of the latter due to incomplete hydrolysis of the ester. Therefore, several new compounds were synthesized which contained a bifunctional molecule between the steroid and the fatty acid. In vivo studies showed an increase in hydrolysis when glycolic acid was taken as the "bridge", compared to the hitherto known esters. Due to the new principle of the steroid-fatty acid connection, in the case of norethisterone, it was possible to introduce tridecanoic acid as lipophilic release controlling substituent without a loss of bioavailability in the baboon. This compound (called: "norethisterone glycotridecanoate") and the corresponding levonorgestral derivative were chosen for a pharmacokinetic-clinical study in women.     

Clonidine antinociceptive activity: Effects of drugs influencing central monoaminergic and cholinergic mechanisms in the rat

Summary Clonidine is able to increase the threshold for vocalisation during stimulation and the threshold for vocalisation after withdrawal of stimulus (vocalisation afterdischarge). These effects of clonidine were investigated after treatment of rats with drugs influencing central monoaminergic and cholinergic mechanisms.Chlorpromazine, atropine and p-chlorophenyl-alanine increased the activity of clonidine at both thresholds while phenoxybenzamine and reserpine pretreatment increased the activity at the threshold for vocalisation only.Yohimbine decreased clonidine activity at both thresholds while 5-HTP and -methyl-p-tyrosine decreased the effects at the threshold for vocalisation afterdischarge. Naloxone did not change the activity of clonidine at either pain response studied.It is concluded from the present findings that influence from several neuronal systems modulate the antinociceptive action of clonidine.The inhibition of the medullary nociceptive response after clonidine might be connected to a decreased activity of noradrenergic neurons. Endogenous noradrenaline seems to be of minor importance in mediating this effect. It is moreover shown that decreased cholinergic receptor activity enhances clonidine antinociceptive action on both medullary and diencephalic-rhinencephalic pain responses. The possible involvement of serotonin in these functional responses after clonidine is also discussed.Data from this investigation was presented at the International Narcotic Research Club Conference, Airlie, Va. 1975.