In vivo and in vitro correlates of food allergy.

Sera of 86 patients clinically sensitive to foods were tested by passive sensitization of human and/or monkey lung (127 tests) and the radioallergosorbent test (RAST) (72 tests), using whole-food antigens; the results were compared with skin (prick) testing. Results of the prick test correlated with history in 76% of cases; lung sensitization correlated with history in 37% and with prick test in 57%; and RAST correlated with history in 54% and prick test in 72%. It is concluded that a very large percentage of adverse reactions to foods are IgE-mediated. The prick test is of use in diagnosis, particularly when combined with RAST; the lung sensitization test is technically impractical and not a reliable indicator. The best diagnostic method is careful history with food challenge and withdrawal and rechallenge; the latter is safe except in patients with a history of violent reaction.     

An excitatory action of 5-Hydroxytryptamine on sympathetic preganglionic neurones

Summary Preganglionic neurones in the fourth thoracic segment of anaesthetized cats fired spontaneously at a rate of about 2/sec. The effects of micro-electrophoretic administration of 5-hydroxytryptamine, noradrenaline, acetylcholine and DL-homocysteic acid on this spontaneous firing were determined. Many cells were excited by 5-hydroxytryptamine (5HT) and DL-homocysteic acid (DLH), a few were depressed by noradrenaline (NAdr), but acetylcholine (ACh) was inactive. The data are consistent with the view that 5HT and NAdr may function as excitatory and inhibitory transmitters which are released from the terminals of descending pathways in the spinal cord.National Science Foundation Postdoctoral Fellow, Riker Fellow.     

Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides

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Immunohistochemical analysis of thymidylate synthase, p16(INK4a), cyclin-dependent kinase 4 and cyclin D1 in colorectal cancers receiving preoperative chemotherapy: significance of p16(INK4a)-mediated cellular arrest as an indicator of chemosensitivity to 5-fluorouracil

High expression of thymidylate synthase (TS) is allegedly associated with the chemoresistance to 5-fluorouracil (5-FU) in colorectal cancers. However, low TS expression does not necessarily imply chemosensitivity. Inactivation of p16(INK4a) correlates with poor prognosis in various cancers. We immunohistochemically evaluated the relationship between the expression of TS, p16(INK4a), CDK4 and cyclin D1 and the effect of 5-FU-based chemotherapy in colorectal cancers. After antigen retrieval, immunoperoxidase staining was performed on the paraffin-embedded, biopsy and surgical specimens of 37 advanced colorectal cancers preoperatively treated with peroral administration of 5-FU derivatives. As a control group, 31 colorectal cancers without preoperative treatment were analyzed. High TS expression was found in 23 (74%) of 31 tumors resected from histological non-responders and in 19 (61%) of 31 controls but in none of six responders. High p16(INK4a) expression was seen in 83% of the responders, 52% of the non-responders and 32% of the controls. The TS-low/p16(INK4a)-high phenotype was noted in 83% of the responders, but only in 3% of the non-responders (P = 0.0001). Induction of p16(INK4a) expression after chemotherapy was predominantly seen in the responders. Neither CDK4 nor cyclin D1 expression was related to the chemotherapeutic effects. In conclusion, the combination of low expression of TS and induction of p16(INK4a) after chemotherapy can be important indicators of the sensitivity to 5-FU-based chemotherapy in colorectal cancers.     

Desensitization of acetylcholine induced inositol 1,4,5-trisphosphate formation in neuroblastoma SH-SY5Y cells following repetitive acetylcholine stimulations

In this study, the desensitization of acetylcholine-induced inositol 1,4,5-trisphosphate [I(1,4,5)P₃] formation, upon short-time prestimulations, was investigated in cultures of human neuroblastoma SH-SY5Y cells. Four repeated stimulations for 10 seconds with 10 μM acetylcholine were necessary to induce a desensitization of the I(1,4,5)P₃ formation. The desensitization was observed 4 hours after the initiation of repetitive stimulations. The same effect was obtained by a single prestimulation with 1 mM acetylcholine. Preincubation of the cells with phorbol 12-myristate 13-acetate (PMA) markedly down-regulated the acetylcholine-induced I(1,4,5)P₃ formation. However, the protein kinase C (PKC) inhibitors H7 and staurosporine did not influence the desensitization induced by four repeated stimulations with 20 μM acetylcholine. These results indicate that the signal transduction can be desensitized following repeated stimulations with sub-maximal concentrations of receptor agonist and although activation of PKC can induce the same down-regulation, PKC is most likely not involved in the desensitization induced by repetitive acetylcholine-stimulations.     

Präkanzerosen des Urothels

Zusammenfassung In der Fluoreszenzdiagnostik [Lichtanregung nach Gabe des physiologischen Hämmetaboliten 5-Aminolävulinsäure (ALA)] erscheinen Präneoplasien und Neoplasien rot fluoreszierend, was wahrscheinlich auf eine tumorzellselektive Anreicherung des intrazellulär aus ALA gebildeten Metaboliten Protoporphyrin IX zurückzuführen ist. Die mit dieser Methode mögliche frühe Detektion von Tumoren und Präneoplasien erlaubt deren genetische Analyse und damit Vergleiche von Aussagen der Fluoreszenz-in-situ-Hybridisierung und Loss-of-heterozygosity-Analyse hinsichtlich Deletionsnachweis und Gensequenzierung. Neue Daten zu Deletionen und Chromosomenaberrationen sowie eine etwa 30%ige Oligoklonalität von Tumoren werden dargestellt. Die tumorselektive Fluoreszenz scheint biochemisch durch Unterschiede im Hämmetabolismus bedingt zu sein. Durch Gen- und Proteinexpressionsanalysen können evtl. weitere, mit dem Hämmetabolismus assoziierte, tumorspezifische Moleküle identifiziert werden.Die geschilderten Arbeiten erfolgten im Rahmen von Unterstützungen durch die Deutsche Krebshilfe 10-1096-Ha und 70.2200-Ba sowie Industriekooperationen von Medac GmbH und metaGen Pharmaceuticals.     

Study on the mechanism of the appearance of noise effects

Summary This study was undertaken to investigate the dose-response relationship between the biological effect and noise exposure, and to consider the mechanism of the appearance of noise effects. Rats were exposed to noise at intensities of 60 dB (A), 80 dB (A) and 100 dB (A) for 240 min and examined for the change of activities of dopamine--hydroxylase (DBH) in serum and adrenal glands. Plasma cyclic adenosine 3,5-monophosphate (c-AMP) levels were also measured. Some rats were given 6-hydroxydopamine (6-OHDA) as a chemical sympathectomyzing agent 20 h before noise exposure in order to consider the mechanism of the appearance of noise effects. By noise exposure, serum DBH activity was significantly (P<0.01) increased at each intensity compared with the control group, but there were no remarkable changes in adrenal DBH activity. Plasma c-AMP level was also significantly elevated in response to the noise stress. When the rats, which had been pretreated with 6-OHDA, were exposed to noise with an intensity of 100 dB (A), the response of serum DBH activity was no longer observed. Therefore it is suggested that the effect due to noise exposure appears through the post-ganglionic sympathetic nerve fiber.     

Changes in glutamate-related enzyme activities in the striatum of the rat following lesion of corticostriatal fibres

Summary The behaviour of enzymes putatively involved in glutamate/aspartate transmitter metabolism (glutamate dehydrogenase, aspartate aminotransferase, alanine aminotransferase,-glutamyltranspeptidase) was studied in the striatum 3, 7, 14 days and 7 weeks after mechanical destruction of corticostriatal fibres. For a period of up to seven days after unilateral lesion, enzyme activities were significantly diminished (by up to 13% based on protein) in the ipsilateral striatum as compared to the striatum of the intact side. Later, the enzyme activities in the ipsilateral striatum recovered. After seven weeks, an increase was observed for glutamate dehydrogenase activity, whereas the activity of alanine aminotransferase showed a transient rise at the end of the second week. The decrease in enzyme levels is interpreted as being attributable to the destruction of nerve endings which are considered to be glutamatergic, interfering with various compensating processes (e.g. glial cell proliferation) which occur with advancing times after lesion.     

Interstitial deletion of band q12 of chromosome 5

A six-months-old girl is presented with psychomotor retardation and multiple congenital malformations. The karyotype done on peripheral blood lymphocytes and skin fibroblasts was found to be 46,XX del(5)(411q13). The parents are consanguineous. Their karyotypes were normal.
The genes for Arylsulphatase B and Hexosaminidase B are not located in band 5q12.     

Polyamines in Trichomonas vaginalis

Trichomonas vaginalis was grown in a modified Bushby's medium and putrescine, spermidine and spermine levels were determined in extracts from 24- and 48-h cultures and also in the culture media. All three polyamines were present in T. vaginalis extracts; the putrescine level and putrescine/spermidine ratio were much higher than those reported for other protozoa or for mammalian tissues. There were no significant differences between 24-h and 48-h amine levels per mg protein in these extracts, but amine levels per cell were higher at 24 than at 48 h. The spent culture media had a much higher putrescine content than corresponding uninoculated media and it was concluded that T. vaginalis secreted putrescine into the culture medium.