Biomedical subjects

Michael Schwarz

Publications and source records attributed to Michael Schwarz.

At least 55 records · Page 3Linked to original sources

PubMed2004

Isolation and identification of novel pyranoanthocyanins from black carrot (Daucus carota L.) juice.

Six novel pyranoanthocyanins were identified by HPLC-ESI-MSn in black carrot (Daucus carota L. ssp. sativus var. atrorubens Alef.) juice. The two major compounds, namely, the vinylcatechol adducts of cyanidin 3-O-(6-O-feruloyl-beta-D-glucopyranosyl)-(1-->6)-[beta-D-xylopyranosyl-(1-->2)]-beta-D-galactopyranoside and cyanidin 3-O-[beta-D-xylopyranosyl-(1-->2)]-beta-D-galactopyranoside, respectively, were isolated by a combination of high-speed countercurrent chromatography with semipreparative HPLC. Their structures were fully elucidated by means of one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry. The four remaining pigments were characterized as the vinylphenol and vinylguaiacol adducts of cyanidin 3-O-[beta-D-xylopyranosyl-(1-->2)]-beta-D-galactopyranoside, the vinylguaiacol adduct of cyanidin 3-O-(6-O-feruloyl-beta-D-glucopyranosyl)-(1-->6)-[beta-D-xylopyranosyl-(1-->2)]-beta-D-galactopyranoside, and the vinylcatechol adduct of cyanidin 3-O-(6-O-sinapoyl-beta-d-glucopyranosyl)-(1-->6)-[beta-D-xylopyranosyl-(1-->2)]-beta-D-galactopyranoside. These compounds are formed during storage of the juice through the direct reaction of either caffeic, ferulic, or coumaric acid with the respective genuine anthocyanins.

Anthocyanins↗

PubMed2004

A constitutively active dioxin/aryl hydrocarbon receptor promotes hepatocarcinogenesis in mice.

The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor regulating transcription of a battery of genes encoding enzymes involved in drug metabolism. Known ligands include polycyclic aromatic hydrocarbons, certain polychlorinated biphenyls, and the polyhalogenated dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin. Both polyhalogenated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin are potent promoters of rodent hepatocarcinogenesis in two-stage initiation-promotion experiments. Although several lines of evidence indicate the involvement of the AhR in toxic effects mediated by polyhalogenated biphenyls and dioxins, its involvement in tumor promotion has not been unequivocally proven. In the present study, a transgenic mouse line expressing a constitutively active AhR (CA-AhR) has been used to investigate the role of the AhR in hepatocarcinogenesis. Male AhR wild-type and CA-AhR-transgenic B6C3F1-mice were treated with a single injection of the hepatocarcinogen N-nitrosodiethylamine at 6 weeks of age and were subsequently kept untreated on control diet. Thirty five weeks after carcinogen treatment, mice were sacrificed, and the prevalence and multiplicity of liver tumors were determined. Whereas only 1 small liver tumor was observed in 15 AhR-wild-type mice, 19 tumors (two >1 cm in diameter) were present in 18 CA-AhR-transgenic mice. This result demonstrates the oncogenic potential of the activated AhR and implicates an important role of the receptor in promotion of hepatocarcinogenesis. A microarray-based gene expression-profiling analysis revealed down-regulation in the liver of CA-AhR-transgenic mice of a cluster of genes encoding heat shock proteins, including GRP78/BiP, Herp1, Hsp90, DnaJ (Hsp40) homologue B1, and Hsp105, which are important for protein folding and quality control.

Animals↗

PubMed2004

Investigations on anthocyanins in wines from Vitis vinifera cv. pinotage: factors influencing the formation of pinotin A and its correlation with wine age.

Pinotage red wines were found to contain a reaction product of malvidin 3-glucoside and caffeic acid, the so-called pinotin A. A total of 50 Pinotage wines from the vintages 1996-2002 were analyzed for the content of pinotin A, malvidin 3-glucoside, caffeic acid, and caftaric acid. Statistical analyses were performed to reveal variations in the content of these compounds and to determine the factors that influence pinotin A formation during wine aging. An exponential increase of the concentration of this aging product was observed with prolonged storage time. The most rapid synthesis of pinotin A was observed in 2.5-4 year old wines, although at this age malvidin 3-glucoside is already degraded to a large extent. This phenomenon is explained by the increased ratio of caffeic acid/malvidin 3-glucoside, which strongly favors the formation of pinotin A and makes side reactions less likely. Pinotin A formation proceeds as long as a certain level of malvidin 3-glucoside is maintained in the wines. In wines >5-6 years old degradation or polymerization of pinotin A finally exceeds the rate of its de novo synthesis.

Anthocyanins↗

PubMed2004

Recovery of semantic word processing in global aphasia: a functional MRI study.

One important issue concerning the recovery of higher cognitive functions-such as word comprehension in aphasia-is to what extent impairments can be compensated for by intact parts of the network of areas normally involved in a closely related function ("redundancy recovery"). In a previous functional MRI investigation, we were able to show that left hemispheric redundancy recovery within a distributed system of related lexical-semantic functions was the most probable basis of recovery of comprehension from transcortical sensory aphasia. The question remained, however, whether redundancy recovery may play a more general role in the recovery of comprehension after large left hemispheric lesions and severe aphasia. We had the possibility, using the same fMRI paradigm, to study seven cases with left middle cerebral artery (MCA) infarction and partial recovery of comprehension > or =6 months after presentation with global aphasia on acute assessment. Lateralization of activation did not differ significantly between patients and controls. The most consistent regions of activation included the left extrasylvian posterior temporal and the right posterior parietal cortex. Recovery of language comprehension was associated predominantly with activations in regions, which were also activated in several normal subjects. We suggest that a redundancy recovery mechanism within multiple representations of closely related functions was more important than take-over of function by previously unrelated areas (vicariation) as the basis of recovery of word comprehension in our patients in spite of extensive left hemispheric damage. We conclude that redundancy within the lexical-semantic system seems to make an important contribution to recovery of comprehension even in severe aphasia.

Acoustic Stimulation↗

PubMed2004

Sound lateralization in Parkinson's disease.

The symptoms primarily associated with Parkinson's disease (PD) are of a motor and cognitive nature, but sensory deficits may also be involved. Previous studies have reported disturbed spatial perception in visual and tactile tasks. We have investigated whether PD patients show deficits in auditory spatial perception. For this purpose, we employed a simple task involving left/right judgments about dichotic stimuli presented with various interaural time differences (ITD). The acuity of sound lateralization was significantly reduced in PD: the just noticeable difference (JND) in interaural time seen in PD patients was about twice that seen for age-matched healthy controls. We propose that this deficit may be related to a potential role of the basal ganglia in spatial hearing functions, as has been suggested by neurophysiological and neuroanatomical studies on animals.

Acoustic Stimulation↗

PubMed2004

Familial thymic cyst.

Thymic cysts are rare lesions of the anterior mediastinum or neck. The majority are asymptomatic, and the remainder are associated mainly with symptoms of dysphagia or dyspnea. Diagnosis is difficult before surgery. Cervical thymic cysts are relatively rare; age at presentation ranges from the neonatal period to adulthood, and the most frequent presenting sign is a lateral neck mass. Mediastinal thymic cysts are more common and account for 1% of all mediastinal masses. They tend to occur in the older age group and are usually detected incidentally on chest X-ray film or computed tomography scans. Dysphagia and dyspnea are the main symptoms. We describe two brothers, aged 5 and 8 years, with mediastinal thymic cysts that presented as low cervical masses and review the embryology, diagnosis and management of thymic cysts.

Child↗

PubMed2004

3-hydroxypropionic acid as a nematicidal principle in endophytic fungi.

3- Hydroxypropionic acid was isolated by bioactivity-guided fractionation of extracts obtained from submerged cultures of several endophytic fungi isolated from above-ground plant organs. This compound showed selective nematicidal activity against the plant-parasitic nematode Meloidogyne incognita with LD50 values of 12.5-15 microg/ml. Activity against the saprophytic Caenorhabditis elegans was fivefold lower. No antimicrobial, cytotoxic or phytotoxic effects were observed. Propionic acid and D- and L-lactic acids were not active against either nematode species. Based on morphological features and ITS, 18S and 28S rDNA analyses, the producing strains were identified as Phomopsis phaseoli isolated from the leaf of a tropical tree, and four strains of Melanconium betulinum isolated from twigs of Betula pendula and B. pubescens in Germany. This is the first report of 3-hydroxypropionic acid in fungi, and of the nematicidal activity of this metabolite.

Animals↗

PubMed2003

Vitisin A content in Chilean wines from Vitis vinifera Cv. Cabernet Sauvignon and contribution to the color of aged red wines.

Vitisin A was prepared from malvidin 3-glucoside and pyruvic acid in model wine medium, isolated by countercurrent chromatography, and purified by preparative high-performance liquid chromatography (HPLC). The synthesized compound was used as a reference standard to quantify vitisin A in Chilean wines from Vitis vinifera cv. Cabernet Sauvignon, including a vertical row of wines from the same vineyard over 16 years. Maximum vitisin A content was reached within the first year of storage. Importantly, up to half of the initial amount of vitisin A in young wines was still present in 15 year old wines. Although vitisin A was found to be much more stable as compared to other monomeric C-4 underivatized anthocyanins, it also slowly degrades after reaching its peak concentration. The "color activity concept" was applied to vitisin A, malvidin 3-glucoside, malvidin 3-(6' '-acetylglucoside), and polymeric pigments isolated by countercurrent chromatography in order to estimate their contribution toward the overall color expression of wines. It was found that vitisin A is only a minor contributor to the visually perceived color of aged red wines (color contribution approximately 5%). The major contributor is the polymeric fraction (color contribution approximately 70-90%).

Benzofurans↗

PubMed2003

WY-14,643-mediated promotion of hepatocarcinogenesis in connexin32-wild-type and connexin32-null mice.

Connexin32 (Cx32) is the major gap junction forming protein in liver and lack of functional Cx32 enhances hepatocarcinogenesis. Many tumour-promoting agents block gap junctional intercellular communication, which may favour clonal expansion of neoplastic cells. We recently demonstrated that liver tumourigenesis is accelerated in Cx32-wild-type but not in Cx32-null mice by the model tumour promoter phenobarbital (PB). In the present study, male Cx32-wild-type and Cx32-null mice were treated with a single injection of 90 micro g/g body wt of N-nitrosodiethylamine (DEN) at 6 weeks of age and were subsequently kept on a diet containing the peroxisome proliferator [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) or on control diet. Thirty-eight weeks after DEN treatment, mice were killed, frozen liver sections were prepared and (pre)-neoplastic lesions were identified by alterations in glucose-6-phosphatase (G-6-Pase) and glutamine synthetase (GS) staining. G-6-Pase-deficient lesions were generally small in size and were observed in all groups of mice. Large focal pre-neoplastic and benign neoplastic lesions, however, which demonstrated increased rather than decreased activity in G-6-Pase were exclusively present in DEN/Wy-14,643-treated mice. G-6-Pase-positive lesions were strongly promoted by Wy-14,643, both in Cx32-wild-type and Cx32-null mice without significant difference in response between mice of the two genotypes. This contrasts G-6-Pase-negative lesions and lesions over-expressing GS, which were both increased by WY-14,643 treatment in number and size in Cx32-wild-type but not in Cx32-null mice. GS-positive lesions from WY-14,643-treated mice harboured beta-catenin mutations, a hallmark of lesions selected during promotion by PB, while G-6-Pase-positive lesions, which displayed negative or diffuse GS staining, did not show beta-catenin mutations. Our results demonstrate significant differences between mouse liver lesions of differing phenotype and genotype in their response towards selection by Wy-14,643 during the promotional phase of hepatocarcinogenesis.

Animals↗

PubMed2003

Pathway leading to the formation of anthocyanin-vinylphenol adducts and related pigments in red wines.

On the basis of observations from Vitis vinifera cv. Pinotage wines and experiments performed in model wine medium, a new chemical pathway responsible for the formation of anthocyanin-vinylphenol adducts in red wines is described. Until now, these pigments have been considered to be reaction products of anthocyanins and vinylphenols, the latter being generated during fermentation by enzymatic decarboxylation of the respective cinnamic acids. The mechanism of the novel pathway, involving intact hydroxycinnamic acid and anthocyanin, is explained. Only cinnamic acids with electron-donating substituents on the aromatic ring, such as coumaric acid, ferulic acid, caffeic acid, and sinapic acid, undergo this conversion, as they stabilize an intermediately formed carbenium ion. Decarboxylation and oxidation of the pyran moieties are the final steps in the generation of the corresponding 4-vinylphenol, 4-vinylguaiacol, 4-vinylcatechol, and 4-vinylsyringol adducts of anthocyanins in red wine.

Anthocyanins↗

PubMed2003

Involvement of the mediodorsal thalamic nucleus in mediating recollection and familiarity.

The mediodorsal (MD) thalamic nucleus is thought to play an important role in memory processes. Distinct hippocampal-thalamic-prefrontal connections have been described as the potential neural substrate for both, recollection and familiarity. The aim of this study was to investigate whether the MD is part of the circuits underlying these two memory components. We assessed the effects of ischemic thalamic lesions with or without MD involvement on performance in a word list discrimination task and standard tests of memory and executive function. Estimates of recollection and familiarity were derived using the dual-process signal-detection model (DPSD). The results revealed impairments in both, recollection and familiarity, after unilateral thalamic damage, with recollection being more affected than familiarity. There were no significant differences in the memory performance of patients with MD lesions compared to patients with ventrolateral-thalamic lesions except for familiarity estimates, which were lower for the latter group. Lesions involving the MD led to recollection deficits, although inspection of individual cases suggested a decrease in both memory components after damage in the medial part of this nucleus. Executive dysfunction was associated with lateral MD lesions and also ventrolateral-thalamic damage. The findings suggest that MD contributes to recollection, with some preliminary evidence of a contribution of the medial MD to familiarity. The small sample size does, however, not yet allow any clear conclusions in this regard. Since damage in the ventrolateral thalamus leads to memory and executive dysfunction, further research is needed to elucidate the role of this thalamic region in cognition.

Brain Ischemia↗

PubMed2003

High incidence of early cholelithiasis detected by ultrasonography in children and young adults with hereditary spherocytosis.

OBJECTIVES: Retrospective cholecystography studies in adults with hereditary spherocytosis (HS) suggested detectable gallstones in 37% to 43% of patients. Since longitudinal studies using biliary ultrasonography are unavailable, the aim of the present study was to determine the incidence of gallstone disease, as detected by biliary ultrasonography, in children and young adults with HS. As individuals with HS who co-inherit Gilbert syndrome have a greater risk of developing gallstones, uridine diphosphate-glucuronyl transferase (UGT-1A) gene polymorphism was also determined. PATIENTS AND METHODS: The authors retrospectively evaluated 44 patients aged 1.4 to 22 years with HS, 12 (27%) of whom underwent splenectomy. Ultrasonography was performed annually starting at the age of 4 years or at the time of diagnosis, if later. RESULTS: Of the 44 patients, 18 (41%) developed cholelithiasis as demonstrated by gallbladder ultrasonography. In most patients (94%) the test first proved positive at age 4 to 13 years. Patients with HS and Gilbert syndrome tended to be younger at the time of cholelithiasis. CONCLUSIONS: Early cholelithiasis was detected in children and young adults with HS. To identify this complication, the authors recommend early annual biliary ultrasonography in HS children, starting at about 4 years of age. In patients with Gilbert syndrome, closer follow-up may be indicated.

Adolescent↗

PubMed2003

Pituitary size in patients with Laron syndrome (primary GH insensitivity).

OBJECTIVE: The purpose of the present study was to investigate whether lifelong secretion of high levels of GH, characteristic of Laron syndrome, leads to an increase in the size of the pituitary gland. METHODS: Eleven patients (six females, five males) with Laron syndrome underwent magnetic resonance imaging of the pituitary region with a system operating at 0.5 T. There were nine adults aged 36-68 Years and two children, a 4-Year-old boy and a 9-Year-old girl. The latter patient had been treated with IGF-I (150-180 mg/kg per day) since the age of 3 Years; all the other patients were untreated. The height of the adenohypophysis was measured on the sagittal images and compared with reference values for age and sex. RESULTS: The height of the adenohypophysis was within the normal range for age and gender in all patients, except for one male, who had a small gland. No congenital anomalies of the pituitary-hypothalamic region were detected. CONCLUSION: Despite the lifelong high levels of GH, no pituitary hypertrophy was detected. The anatomy of the pituitary-hypothalamic region in Laron syndrome is normal.

Adult↗

PubMed2003

[Value of spiral CT and MRI (1.5 T) in preoperative diagnosis of tumors of the head of the pancreas].

OBJECTIVE: Prospective comparison study of helical computed tomography (HCT) and magnetic resonance imaging (MRI, 1.5-tesla field strength) with regard to their role in planning surgical therapy in a defined, homogeneous patient collective with tumors of the pancreatic head. PATIENTS AND METHODS: Sixty-one patients with clinical/ultrasound evidence of tumor were examined by HCT and MRI. Findings were compared with surgical anatomy and histology using a data documentation sheet. Factors evaluated included the malignancy of the tumors and the probability of correct diagnosis in relation to tumor size, as well as the occurrence of lymph node and distant metastases, arterial and portal-venous infiltration, extrapancreatic infiltration, determination of resectability and tumor staging (TNM classification). These factors were compared on the basis of their respective sensitivity, specificity, negative and positive predictive value and accuracy. RESULTS: Malignancy was correctly diagnosed by HCT and MRI in 82% and 77%, respectively, with a corresponding sensitivity for malignancy of 86% and 68%. Tumors with diameters > 2 cm were detected in 100% of cases by HCT and in 88% by MRI, while tumors with diameters < 2 cm were correctly diagnosed by HCT and MRI in 60% and 40% of cases. Respective rates of correct diagnosis by HCT and MRI were 80% and 66% for extrapancreatic infiltration; 76% and 79% for pancreatic cysts; 87% and 87% for calcifications; and 77% and 92% for atrophy. The diagnostic accuracy for vascular infiltration by HCT and MRI stood at 59% and 77% with sensitivities of 88% and 75%, respectively. Local resectability was correctly determined by HCT in 71%, by MRI in 62% of cases. Lymph node metastases were correctly identified by HCT and MRI with an accuracy of 76% and 72%, while distant metastases were correctly diagnosed by HCT and MRI with an accuracy of 93% and 93%. Correct T stage was identified by HCT in 66%, by MRI in 60%. HCT tended to assign patients to a higher T stage than later determined by surgery and/or histology. CONCLUSION: Our data do not indicate a clear superiority for either HCT or MRI in the diagnosis of pancreatic malignancies.

Adult↗

PubMed2002

Overexpression of glutamine synthetase is associated with beta-catenin-mutations in mouse liver tumors during promotion of hepatocarcinogenesis by phenobarbital.

Phenobarbital (PB) is an antiepileptic drug that promotes hepatocarcinogenesis in rodents when administered subsequent to an initiating carcinogen like N-nitrosodiethylamine (DEN). In the mouse, the promotional effect of PB on liver tumor development results from a selective stimulation of clonal outgrowth of hepatocytes harboring activating mutations in the beta-catenin gene. Because glutamine synthetase (GS) has recently been shown to be a putative transcriptional target of beta-catenin, expression of GS during PB-mediated promotion of mouse hepatocarcinogenesis was investigated. Preneoplastic and neoplastic liver lesions were induced in 6-week-old male mice by a single injection of 90 micro g/g body weight of DEN, and groups of mice were subsequently kept on PB-containing (0.05%) or control diet for 39 weeks. In PB-treated mice, 46 of 51 lesions ( approximately 90%) were GS-positive in contrast to only 16 of 46 ( approximately 35%) in mice not treated with PB. Approximately 33% of liver was occupied by neoplastic tissue in PB-treated mice, of which >80% was GS positive. By contrast, only approximately 3.5% of liver consisted of neoplastic tissue in mice treated with DEN only, and approximately 25% of this was GS positive. We have previously shown that beta-catenin mutations are present in approximately 80% of liver tumors from PB-treated mice but are absent in liver tumors from mice treated with DEN only. By analyzing a panel of larger liver tumors, we now observed that tumors harboring beta-catenin mutations were GS positive, whereas tumors without beta-catenin mutations were GS negative. Similarly, tumors from an additional mouse carcinogenicity experiment where PB inhibited rather than promoted hepatocarcinogenesis were mostly GS negative. These data suggest that promotion of hepatocarcinogenesis by PB confers beta-catenin-mutated tumor cells with a selective advantage by up-regulation of GS expression.

Animals↗

PubMed2002

Modification of a functional motor task by non-consciously perceived sensory stimuli.

In recent years it has been suggested that processing of visual information is divided between a ventral stream, responsible for object recognition and conscious processing of object properties, and a dorsal stream mediating automatic integration of visual information into a motor task. We used metacontrast masking to prevent conscious perception of visual cues concerning the load of an object to be lifted in a precision grip. It was found that when such non-consciously perceived cues warned of a load change, they allowed the subjects to produce the grip force profile appropriate to the new load. It is concluded that non-consciously perceived visual information can be utilised to adapt a functional motor task to actual conditions.

Adult↗

PubMed2002

Recovery of semantic word processing in transcortical sensory aphasia: a functional magnetic resonance imaging study.

In a previous functional magnetic resonance imaging (fMRI) study with normal subjects, we demonstrated regions related to conceptual-semantic word processing around the first frontal sulcus (BA 9) and the posterior parietal lobe (BA 7/40) in agreement with several previous reports. We had the possibility, using the same fMRI paradigm, to study two consecutive cases with left middle cerebral artery (MCA) infarction (RC and HP) and lesions affecting either solely the pre-frontal (HP) or both the pre-frontal and posterior parietal part of the network activated in normal subjects (RC). Both patients showed transcortical sensory aphasia (TSA) on acute assessment. This contradicts classical disconnection accounts of the syndrome stating intact conceptual representations in TSA. Their recovery of language comprehension was associated with activation of a left hemispheric network. Mainly activations of left perilesional pre-frontal regions (RC), left Wernicke's area (RC and HP) or the left posterior middle and inferior temporal cortex (HP) were demonstrated in the TSA patients. The latter findings suggest that in our cases of TSA functional take-over has occurred in regions with related functions ('redundancy recovery') rather than in previously unrelated areas ('vicarious functioning'). Our data support distributed models of conceptual-semantic word processing and multiple left hemispheric representations of closely related functions.

Adult↗

PubMed2002

Laron syndrome abnormalities: spinal stenosis, os odontoideum, degenerative changes of the atlanto-odontoid joint, and small oropharynx.

BACKGROUND AND PURPOSE: Patients with Laron syndrome have an inborn growth hormone resistance. We investigated abnormalities in the upper airways and cervical spine in patients with Laron syndrome. METHODS: We prospectively examined 11 patients (one child aged 9 years and 10 adults aged 36-68 years), 10 of whom underwent MR imaging of the spine or head; nine, radiography of the cervical spine; and four, CT of C1-C2. The width of the spinal canal was evaluated visually and quantitatively and compared with reference values. The smallest diameter of the oropharynx and the thickness of the palate were measured and compared with reference values. Nine age-matched female patients referred for MR imaging for unrelated reasons served as control subjects. RESULTS: Cervical spinal stenosis was present in seven of the adult patients, within a confidence interval of 95%. Anomaly of the dens compatible with os odontoideum was present in three patients, causing focal myelomalacia in two. The atlanto-odontoid joint showed osteoarthritic changes in six of the adult patients. The mediolateral diameter of the oropharynx was significantly smaller in the patients with Laron syndrome than in the control subjects (P <.005). There was no difference in the thickness of the soft palate. CONCLUSION: Patients with Laron syndrome develop significant narrowing of the cervical spinal canal and early degenerative changes of the atlanto-odontoid joint. Laron syndrome is associated with os odontoideum causing myelomalacia. The dimensions of the oropharynx are small. Patients may be prone to neurologic morbidity and sleep disturbances. Routine MR imaging of the cervical spine is recommended in these patients.

Adult↗