Human Aldehyde Dehydrogenase: Kinetic Identification of the Isozyme for Which Biogenic Aldehydes and Acetaldehyde Compete

Michaelis constants and maximal velocities for phenylacetaldehyde (a metabolite of phenylethylamine), 3,4-dihydroxyphenylacetaldehyde (a metabolite of dopamine), 5-hydroxyindole acetaldehyde (a metabolite of serotonin), and 3,4-dihydroxyphenylglycolaldehyde (a metabolite of epinephrine and norepinephrine) have been determined for both cytoplasmic (E1) and mitochondrial (E2) isozymes of human liver aldehyde dehydrogenase (EC 1.2.1.3). Kinetic constants with biogenic aldehydes have never been previously determined for individual homogeneous isozymes of aldehyde dehydrogenase from any species. Mathematical treatment of these constants suggests that competition with acetaldehyde during alcohol metabolism would severely inhibit dehydrogenation of biogenic aldehydes with the mitochondrial and not the cytoplasmic isozyme of human liver aldehyde dehydrogenase.     

Aripiprazole augmentation in treatment-resistant depression.

BACKGROUND: Evidence is accumulating to support the use of atypical neuroleptics as adjunctive treatment for refractory mood disorders, although there are currently no published data on the efficacy of an atypical neuroleptic in treatment-resistant depression when a previous trial of drug from the same class has failed. The authors hypothesized that aripiprazole would be efficacious in augmenting antidepressant treatment in resistant patients with non-psychotic unipolar depression who had previously failed a trial of another atypical neuroleptic. METHODS: This study was a retrospective chart review of the efficacy of aripiprazole augmentation in 30 treatment-resistant unipolar depression patients who had failed multiple previous antidepressant trials and had also failed augmentation with at least one other atypical neuroleptic. Prospective Global Assessment of Functioning and Clinical Global Impressions-Improvement scores were completed on each patient throughout treatment. RESULTS: Utilizing an intent-to-treat analysis (including 9 patients who dropped out prior to completion of 6 weeks), 46.7% (14/30) patients were rated much improved or very much improved with treatment. This improvement negatively correlated with Thase-Rush staging of treatment resistance. GAF scores also showed a significant improvement. Six of the 14 patients who initially improved subsequently relapsed (yielding a long-term net response rate of 26.7%). CONCLUSION: Aripiprazole may be effective as an antidepressant augmentation agent in highly treatment resistant patients who had failed a prior trial of another atypical neuroleptic.     

Lumbosacral glioblastoma and leptomeningeal gliomatosis complicating the course of a cervicothoracic astrocytoma WHO grade II

CASE REPORT: The reported female patient underwent sub-total resection of an intra-medullary cervicothoracic astrocytoma classified as WHO grade II in 1984 at the age of 18 months and received local irradiation. In 1989, a local recurrence was diagnosed and a partial resection was performed. Sixteen years later, a small recurrent cervicothoracic tumour was found and spinal seeding to the equine nerve roots and the left cerebellar cortex was apparent on MRI. The patient was implanted with a ventriculoperitoneal shunt for a pseudo-tumour cerebri producing papilloedema, which eventually lead to amaurosis. After an extended biopsy, the invasive lumbosacral tumour was classified as glioblastoma multiforme. Two months later, the patient died after rapid progression of the caudal cranial nerve dysfunction. DISCUSSION AND CONCLUSION: Anaplastic progression and dissemination of spinal astrocytomas even two decades after initial diagnosis and treatment are rare. Therapies and diagnostic follow-up strategies are discussed.     

Diagnostic subgroups of developmental dyslexia have different deficits in neural processing of tones and phonemes.

The present study addressed auditory processing in 8-11-year-old children with developmental dyslexia by means of event-related brain potentials (ERP). Cortical sound reception was evaluated by recording N250 responses to syllables and tones and cortical sound discrimination by analyzing the mismatch negativity (MMN) to syllable and tone changes. We found that both cortical sound reception and sound discrimination were impaired in dyslexic children. The analysis of the data obtained from two dyslexic subgroups, Dyslexics-1 being impaired in non-word reading (or both non-word and frequent word reading) and Dyslexics-2 in frequent word reading but not in non-word reading, revealed that the MMN was specifically diminished in the latter group whereas it was normal-like in Dyslexics-1. However, no differences were found between these subgroups in sound reception as indicated by the responses elicited by the standard stimuli. These results show that different diagnostic subgroups of dyslexics have different patterns of auditory processing deficits as suggested by similarly impaired sound reception in both dyslexic groups and the sound-discrimination impairment specific to one of the groups.     

Untersuchungen über die Coccidieninfektion bei Nestlingen

Zusammenfassung Eine größere Anzahl von Nestlingen (269) wurde auf Coccidien-Befall hin untersucht. Es handelt sich vorwiegend um Vertreter von Singvogelarten (206) und Haustauben (63). Die Nestjungen waren hier bis zu 17,1% von Coccidien befallen. Die Infektionen erwiesen sich durchweg als sehr schwach. Unter normalen Verhältnissen treten akute Coccidiose-Fälle bei Nestlingen nicht auf.     

Histopathologic changes in metabolic bone disease

Metabolic bone disease encompasses a heterogeneous group of disorders that influence skeletal metabolism and structure. They are generally diagnosed at an advanced stage and manifest clinically with stunted skeletal growth in children and pathologic fractures in adults. Biochemical markers for bone metabolism are equivocal and microscopic examination of labeled bone remains the gold standard for the diagnosis and accurate monitoring of the response to therapy. This article reviews the role of microscopic bone changes in the diagnosis and management of metabolic bone disease.     

New x-ray tube performance in computed tomography by introducing the rotating envelope tube technology

The future demands of computed tomography imaging regarding the x-ray source can be summarized with higher scan power, shorter rotation times, shorter cool down times and smaller focal spots. We report on a new tube technology satisfying all these demands by making use of a novel cooling principle on one hand and of a novel beam control system on the other hand. Nowadays tubes use a rotating anode disk mainly cooled via radiation. The Straton x-ray tube is the first tube available for clinical routine utilizing convective cooling exclusively. It is demonstrated that this cooling principle makes large heat storage capacities of the anode disk obsolete. The unprecedented cooling rate of 4.8 MHU/min eliminates the need for waiting times due to anode cooling in clinical workflow. Moreover, an electronic beam deflection system for focal spot position and size control opens the door to advanced applications. The physical backgrounds are discussed and the technical realization is presented. From this discussion the superior suitability of this tube to withstand g-forces well above 20 g created by fast rotating gantries will become evident. Experience from a large clinical trial is reported and possible ways for future developments are discussed.     

Immature B cells from human and mouse bone marrow can change their surface light chain expression

The capacity of bone marrow-derived surface immunoglobulin-positive (sIg⁺) human and mouse immature B cells, generated either in vitro or in vivo, to change their light (L) chain expression, has been assayed by the number of cells which change in vitro from one type of L chain to the other type, or to no sIg at all. Immature sIg⁺ B cells were generated in vitro from sIg^? precursor cells from human or mouse bone marrow. The immature sIg⁺ cells expressed RAG-1. Human sIg⁺ cells expressed xfr; and λ L chains in ratios between 1:1 and 3:1, whereas in mouse cells, this ratio ranged from 10:1 to 20:1. Upon reculture of the human and mouse xfr;⁺sIg⁺ cells, about half of them remained xfr;⁺, a quarter became λ⁺, and another quarter became sIg^?. Between 1 and 3% expressed both xfr; and λ chains. Of the human λ⁺ cells, about two-thirds remained λ⁺, only 1 to 2% became xfr;⁺, while the other third became sIg^?. Again, between 1 and 3% expressed both xfr; and λ L chains. These results indicate that expression of sIgM in the B cell membrane does not terminate L chain gene rearrangement, and that some order exists in xfr; versus λ gene rearrangements. Hence, human and mouse xfr;⁺ immature B cells can become λ⁺, but very few of the λ⁺ cells can become xfr;⁺, and both can become sIg^?. Further, human CD10⁺/sIg⁺ xfr;⁺ and λ⁺ cells and mouse B220^low/sIg^low xfr;⁺ cells enriched from bone marrow, i.e. immature B cells differentiated in vivo, changed their Ig phenotype upon in vitro culture, but in lower frequencies. By contrast, human and mouse mature B cells did not change their L chain or Ig phenotype. Hence, at least a part of the sIg⁺ immature B cells in bone marrow retain the capacity to change their L chain and Ig phenotype, and this capacity is lost when they become mature, peripheral B cells.     

Der Einfluss von Trijodthyropropionsäure und Trijodthyroessigsäure auf den Jodumsatz der Schilddrüse des Menschen

Zusammenfassung 1. Der Jodumsatz gesunder Schilddrüsen und blander Strumen wurde durch eine ein- bis dreiwöchige Medikation von täglich 0,5–2,0 mg Trijodthyropropion- oder Trijodthyroessigsäure per os gehemmt. Kleinere Dosen ließen diesen Einfluß bis auf eine Ausnahme vermissen, bei zwei blanden Strumen blieben auch 1,0 mg des Essigsäurederivates täglich ohne Wirkung. Der Sauerstoffverbrauch und Hormonjodgehalt des Blutes wurden durch die Zufuhr der beiden Metaboliten in keinem dieser Fälle wesentlich verändert.2. Zwei Kranke mit extrathyreoidalem Hypometabolismus wiesen insofern noch besondere Verhältnisse auf, als durch 0,1 mg Trijodthyropropionsäure bzw. 1,0 mg Trijodthyroessigsäure täglich der Sauerstoffverbrauch eindeutig zunahm und der Hormonjodspiegel einmal abfiel.3. Der thyreoidale Jodumsatz von Hyperthyreosen, einer euthyreotischen endokrinen Ophthalmopathie und einer Struma mit Rückstoß-Phänomen wurde durch die beiden Verbindungen nicht beeinflußt.Zwischen der Rückwirkung von genuinen Schilddrüsenhormonen und ihren Metaboliten auf den Jodumsatz der Schilddrüse bestehen erhebliche quantitative und gelegentlich auch qualitative Unterschiede. Deren Bedeutung wird erörtert.Die Untersuchungen wurden mit freundlicher Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt.     

Vom Werden und Wesen des Ärztlichen Berufes

Ohne ZusammenfassungDer Tag eines überlasteten Klinikers ist von zwingenden Pflichten restlos besetzt. Nur in kargen, seinem Beruf mühsam abgerungenen Abendstunden beschäftigte sich ERICH MEYER jahrelang mit dem Problem der vorliegenden Schrift: Vom Werden und Wesen des ärzbtlichen Berufes.Immer wieder unterbrach die gesetzesstarke menschliche Pflicht seines Berufes die ersehnte Sammlung zu seinem geplanten Werk, das er in der Stellungnahme zu den vielartigen Auffassungen der Gegenwart eine Entgegnung nannte. Alle Wege der Klärung wollte er gehen. Oft saß er bis in die Nacht hinein an dieser Arbeit, las eine Fülle historischer und philosophischer Bücher; nur weniges von den gewonnenen Anregungen und Zitaten konnte in diese Schrift aufgenommen werden. Vor allem beabsichtigte er ein stärkeres Gewicht auf die philosophischen Ausführungen zu legen. So hat er in letzter Zeit über das Verhältnis von mechanistisch-kausaler und teleologischer Betrachtungsweise des menschlichen Körpers eindringlich forschend, neue Anschauungen gewonnen. Er betonte als Gegengewicht gegen die aus philosophischer Halbbildung entstandenen Modeanschauungen über das Wesen der Medizin die Notwendigkeit einer philosophischen Durchbildung des Mediziners, durch die er sich ein schärferes Bewußtsein von der Tragweite und der Bedeutung klarer Begriffe erwerben müsse.Ein tragisches Geschick, das sein tatenreiches und tatenbereites Leben zerstörte, ließ ihn auch diese Arbeit nicht beenden. Er hinterließ nur Bruchstücke und Skizzen, die noch nicht zu einem organischen Ganzen durchgearbeitet waren. So blieb diese Schrift nur ein Entwurf, der aber dennoch seinen innerlichen Standpunkt klarstellt, der seine Stimme trägt, die nicht verstummen soll, die lebendig werben soll in dem Sinne des Mottos, das er zu dieser seiner Arbeit wählte:Wer aber durchschaut in das vollkommene Gesetz der Freiheit, und darin beharrt, und ist nicht ein vergeßlicher Hörer, sondern ein Täter, derselbe wird selig sein in seiner Tat. Buch Jacobi 1–2.