Search PubMed⌕ Search

Biomedical subjects

A Schönberger

Publications and source records attributed to A Schönberger.

At least 19 recordsLinked to original sources
PubMed2001

The first polymer-assisted solution-phase synthesis of deoxyglycosides.

[reaction--see text] A glycosylation protocol for the synthesis of 2-deoxyglycosides has been developed which is based on the use of polymer-bound reagents. Glycals are transformed into 2-iodoglycosyl acetates using polymer-bound bis(acetoxy)iodate(I) complex (1). Activation of the anomeric center is achieved by employing polymer-bound silyl triflate (2). In the presence of different glycosyl acceptors, 2-deoxy-2-iodoglycosides are generated in very good yields. Furthermore, it is shown that this method can be embedded in multistep sequences toward glycosylated testosterone and rhodinosyl-olivosyl-olivoside.

Carbohydrate Sequence↗
PubMed1996

Inhibitory effect of ethyl oleate hydroperoxide and alcohol in photosensitized oxidative DNA damage.

Xanthone-sensitized photo-oxidation of guanine in calf thymus DNA and in the nucleoside 2'-deoxyguanosine has been investigated in the presence of various additives, with major emphasis on hydroperoxides. The formation of the guanine oxidation products 7,8-dihydro-8-oxoguanine (8-oxoGua), which is a marker for oxidative DNA damage, and 2,2-diamino-4-[(2-deoxy-beta-D-erythro-pentofuranosyl)amino]-5(2H)-oxazo lone (oxazolone) was monitored quantitatively by high performance liquid chromatography electrochemical or fluorescence analysis. Irradiation (350 nm) of calf thymus DNA in the presence of xanthone as sensitizer afforded 8-oxoGua in 1.4% yield. The ethyl oleate hydroperoxide 1a and its alcohol 1b inhibit the formation of 8-oxoGua very efficiently (up to 85%). Even the structurally simple t-butyl hydroperoxide and the physiologically relevant hydrogen peroxide exhibit strong inhibition of photosensitized oxidation of guanine in DNA and in the nucleoside, while t-butanol and the allylic alcohols 3b and 4 do not. Hydroperoxides in general quench type I-sensitized (benzophenone, xanthone) photo-oxidation of guanine, but not that of rose bengal, a predominant type II sensitizer. The inhibiting effect is explained by H abstraction of the electronically excited carbonyl chromophore from the additive. The biological relevance of these findings should be seen in the potential protecting role of lipid hydroperoxides and their corresponding alcohols against oxidative stress.

Animals↗
PubMed1995

Formation of 7,8-dihydro-8-oxoguanine in the 1,2-dioxetane-induced oxidation of calf thymus DNA: evidence for photosensitized DNA damage by thermally generated triplet ketones in the dark.

Isolated calf thymus DNA was treated with the 1,2-dioxetanes 3-acetoxymethyl-3,4,4-tri-methyl-1,2-dioxetane, 2,3-dimethylbenzofuran dioxetane, 3-hydroxymethyl-3,4,4-trimethyl-1,2-dioxetane (HTMD), 3,3,4,4-tetramethyl-1,2-dioxetane and 3,4,4-trimethyl-1,2-dioxetane (TrMD), which on thermal decomposition generate triplet-excited carbonyl products. To monitor quantitatively the formation of the mutagenic oxidation product 7,8-dihydro-8-oxoguanine (8-oxoGua), a sensitive and selective HPLC electrochemical assay was used after acidic hydrolysis (HF/pyridine) of the dioxetane-treated DNA. High yields of 8-oxoGua (up to ca 4% of the available guanine) were obtained for HTMD and TrMD. Both were investigated in detail with respect to effects of concentration, time and temperature. The oxidative reactivity of 1,2-dioxetanes was compared with several type I (benzophenone and riboflavin) and type II (methylene blue and rose bengal) photooxidants and disodium 1,4-etheno-2,3-benzodioxin-1,4-dipropionate as a chemical source of singlet oxygen. The persistence of 8-oxoGua towards oxidation by HTMD was examined in the reaction with 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodGuo) and with oxidized DNA. It was shown that, indeed, 8-oxoGua is consumed in the oxidized DNA on prolonged exposure to an excess of HTMD. The reaction of 8-oxodGuo with HTMD afforded the two 4R* and 4S* diastereomers of 9-(2-deoxy-beta-D-erythropentofuranosyl)-4, 8-dihydro-4-hydroxy-8-oxoguanine as main oxidation products. Trapping experiments with tert-butanol confirmed that hydroxyl radicals are not involved, whereas the use of the triplet quenchers sodium 9,10-dibromo-anthracene-2-sulfonate and 2,3-diazabicyclo[2.2.1]hept-2-ene established that triplet-excited states are mainly responsible for the observed DNA oxidation through type I action (electron transfer chemistry). The role of singlet oxygen was tested by means of deuterium isotope effects in D2O versus H2O, but no definitive conclusion could be reached in regard to the involvement of 1O2 in these oxidations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Genotoxicity studies of benzofuran dioxetanes and epoxides with isolated DNA, bacteria and mammalian cells.

1,2-Dioxetanes, very reactive and high energy molecules, are involved as labile intermediates in dioxygenase-activated aerobic metabolism and in physiological processes. Various toxicological tests reveal that dioxetanes are indeed genotoxic. In supercoiled DNA of bacteriophage PM2 they induce endonuclease-sensitive sites, most of them are FPG protein-sensitive base modifications (8-hydroxyguanine, formamidopyrimidines). Pyrimidine dimers and sites of base loss (AP sites) which were probed by UV endonuclease and exonuclease III are minor lesions in this system. While the alkyl-substituted dioxetanes do not show any significant mutagenic activity in different Salmonella typhimurium strains, heteroarene dioxetranes such any significant mutagenic activity in different Salmonella typhimurium strains, heteroarene dioxetanes such as benzofuran and furocoumarin dioxetanes are strongly mutagenic in S. typhimurium strain TA100. DNA adducts formed with an intermediary alkylating agent appear to be responsible for the mutagenic activity of benzofuran dioxetane. We assume that the benzofuran epoxides, generated in situ from benzofuran dioxetanes by deoxygenation are the ultimate mutagens of the latter, since benzofuran epoxides are highly mutagenic in the S. typhimurium strain TA100 and they form DNA adducts, as detected by the 32P-postlabelling technique. Our results imply that the type of DNA damage promoted by dioxetanes is dependent on the structural feature of dioxetanes. Furthermore, the direct photochemical DNA damage by energy transfer, i.e., pyrimidine dimers, plays a minor role in the genotoxicity of dioxetanes. Instead, photooxidation dominates in isolated DNA, while radical damage and alkylation prevail in the cellular system.

Alkylating Agents↗
PubMed1988

Alterations of melatonin secretion in atopic eczema.

The circadian rhythm of melatonin secretion of the pineal gland can be disturbed in a variety of clinical conditions and diseases including some psychic disorders. To study the rhythmic behaviour of melatonin secretion in atopic eczema (AE), melatonin serum levels were measured every 2 h, starting at 8 a.m. in 18 patients suffering from severe AE. In 6 patients exhibiting low serum levels of melatonin, the circadian melatonin rhythm was found to be abolished. In 8 patients a diminished nocturnal melatonin increase was observed compared with the controls (n = 40). Only 4 patients showed a normal secretion pattern of melatonin. The results provide some evidence of a dysfunction of the pineal gland in AE, possibly due to a partially reduced activity of the sympathetic nervous system being involved in the control of melatonin secretion.

Adolescent↗
PubMed1988

[Are shifts in circadian cortisol rhythm an endocrine symptom of atopic eczema?].

Marked nocturnal pruritus in patients with atopic eczema (AE) may depend partly on alterations in circadian neuroendocrine rhythms, e.g. cortisol rhythm. We analysed the serum cortisol levels every 2 h between 8 p.m. and 8 a.m. and at 2 p.m. (profile I) in 20 adult in-patients with florid AE not pretreated with any systemic corticosteroid or ACTH therapy (profile I). The results were compared with those recorded in 19 healthy women. In 14 patients we checked the profiles again after marked improvement of AE (profile II). On profile I, the lowest cortisol levels were after midnight for 9 of the 20 patients, while on profile II this was true for 12 of the 14 tested. The mean cortisol levels over the period examined were found to be approximately the same for patients and controls for profile I, yet the mean level on profile II was found to be lower. The mean time interval between minimum and maximum cortisol levels was shorter in patients with AE than in controls (8.5 h), and was shorter still on profile II (4.6 h). The shift in the serum cortisol minimum after midnight resulted in an extremely steep rise in the cortisol level between the level in the late hours of the night, and the 24 h-maximum in the early morning hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

[Disorders of thermoregulation in adaptation to external cold and heat stimuli in patients with atopic eczema].

Patients suffering from atopic eczema (AE) often exhibit disturbances of various neurovegetative (in particular, vasomotoric) skin functions. Thus, in 21 patients with AE we studied the response of the skin of one forearm to standardized 15-min exposure of the other arm to a cold and a warm bath (17 degrees-18 degrees C and 40 degrees-41 degrees C respectively). The results were compared with those in 23 age- and sex-matched healthy controls under similar environmental conditions. In most patients, during exposure of one forearm to warmth the skin temperature of the contralateral forearm remained unchanged or decreased slightly, whereas exposure to cold induced either a slight rise in skin temperature or an almost indiscernible decrease. In contrast to the normal temperature reaction of the non-exposed forearm to warmth exposure of the contralateral arm in most controls, our findings in atopic patients indicated a "rigid" or even "paradoxical" response to thermic stimuli. This abnormal pattern of thermoregulation may reflect an intrinsic disturbance of the peripheral and hypothalamic autonomous system involved in the pathogenetic conditions of AE.

Adolescent↗
PubMed1988

[Quantified determination of dermographism in patients with atopic eczema].

The usual method of checking dermatographism (D), which is typically white in atopic eczema (AE), allows only a qualitative rating. To allow reproducible quantification of D we have developed an easily used instrument, called a Dermographometer. This can be fitted with one to three blunt tapered metal bars of different weights applying a constant stretching pressure over the whole skin areas to be examined or different pressures at isolated points. We used this device to study D in 27 patients with AE and in 20 healthy controls. Of the 27 patients, 21 had white D, 2, red D, and 4, none at each pressure applied. In 18 of the controls D was red. In addition, the two groups differed significantly in the time to onset and the duration of the D elicited, which was much longer in patients with AE. Simultaneous and constant application of distinct grades of pressure for quantitative dermatographometry is a method that can reliably be used for the study of inter- and intraindividual variation in vascular reactivity in the course of various dermatoses, especially.

Adolescent↗
PubMed1987

[Classification and scope of clinical variations of Melkersson-Rosenthal syndrome].

Apart from the apparent trias of oro-facial swellings, facial paresis, and lingua plicata (LP), Melkersson-Rosenthal syndrome (MRS) comprises a variety of complex signs and symptoms. During the last 18 years, 73 patients suffering from MRS were admitted to our hospital. Re-examination of 42 out of these patients and evaluation of all data available proved preceding facial paresis(es) in only 34% of all cases and LP of various degrees in 52%. In more than 80%, however, we found vasomotoric, sialo-secretory, or other neurovegetative "minor signs", locally and/or temporally connected with swellings of either skin or mucosa. Since such minor signs are essential for the diagnosis and the understanding of both "complete" and "incomplete" forms of MRS (either associated with or without typical cheilitis granulomatosa), we worked out a classification of MRS considering the dermal, neurological, and neurovegetative affections observed in our cases and according to the relevant literature. A systematic classification like this, which takes into account the diagnostic signification of the findings, allows exact recognition of "incomplete" forms of MRS and represents a conditio sine qua non with regard to family studies and the follow-up of patients concerned.

Diagnosis, Differential↗
PubMed1987

[Site-specific incidence of benign and precancerous leukoplakias and cancers of the oral cavity].

The distribution patterns of benign and precancerous oral leukoplakias as well as oral cancer were investigated in 547 patients. The most frequently affected site was the buccal mucosa, the rarest localization was the floor of mouth. 96% of buccal lesions were benign, 4% were precancerous or cancerous. In contrast, 68% of the lesions on the floor of the mouth were precancerous or cancerous. Our results indicate, that the localization of leukoplacic lesions in the oral cavity is an important hallmark of their dignity.

Adolescent↗
PubMed1986

[Glossodynia--indication for patch testing?].

100 patients suffering from glossodynia without pathologic changes of the oral mucosa and 16 patients with suspected allergic contact stomatitis underwent patch testing using standard patch test and dental materials. The results were compared with those of patients in dental occupations suffering from hand eczema. As there is no clinical relevance of allergens in patients with glossodynia, patch testing seems to be unnecessary. On the other hand, patch test results of patients with stomatitis and dentures often suggest a causal allergy. In most of those cases, this was confirmed by complete healing after changing the denture bases, whereas in glossodynia such replacements never brought about a convincing improvement of the symptoms.

Dentures↗
PubMed1986

[Thermographico-histologic study of the lymph drainage areas in malignant melanoma].

In an investigation including 176 patients with malignant melanoma (MM) of the skin, the preoperative infrared telethermograms (IR-TT) obtained from the draining lymph node area were compared with the clinical and histologic data on lymph nodes removed by dissection. In 19 out of 92 cases with high-risk MM subjected to primary tumor excision and draining lymph node dissection, metastatic involvement of one or more lymph nodes was found histologically. In 18 of 19 cases (= 95%) with metastatic spread of MM, there was a considerable degree of hyperthermic radiation in the respective axillary or inguinal area. On palpation, only 13 of 19 patients (= 68%) showed conspicuous lymph node enlargement. The histologic sections of the lymph nodes of the above 18 patients with both regional spread of MM and hyperthermia were reexamined in order to compare the extent of tumor involvement with the q-classification of IR-TT. There was a remarkable correlation between an increase in the number of macrometastases (and conversely, a drop in the number of micrometastases) and the grades of regional hyperthermia.

Carcinoma in Situ↗