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Biomedical subjects

T Wittmann

Publications and source records attributed to T Wittmann.

At least 19 recordsLinked to original sources
PubMed2004

Complete characterization of a plasma mirror for the production of high-contrast ultraintense laser pulses.

Improving the temporal contrast of ultrashort and ultraintense laser pulses is a major technical issue for high-field experiments. This can be achieved using a so-called "plasma mirror." We present a detailed experimental and theoretical study of the plasma mirror that allows us to quantitatively assess the performances of this system. Our experimental results include time-resolved measurements of the plasma mirror reflectivity, and of the phase distortions it induces on the reflected beam. Using an antireflection coated plate as a target, an improvement of the contrast ratio by more than two orders of magnitude can be achieved with a single plasma mirror. We demonstrate that this system is very robust against changes in the pulse fluence and imperfections of the beam spatial profile, which is essential for applications.

Journal Article↗
PubMed2004

Regional differences in the manifestation of gastrointestinal motor disorders in type 1 diabetic patients with autonomic neuropathy.

OBJECTIVE: The aim of this work was to establish the prevalence and severity of different gastrointestinal symptoms and their relationships to esophageal, gastric and recto-anal motor disturbances by manometry in patients with Type 1 diabetes mellitus and autonomic neuropathy. PATIENTS AND METHODS: Sixteen patients (mean age: 53.4 +/- 14.9 years) with long standing type 1 diabetes mellitus (mean diabetes duration: 22.1 +/- 14.7 years) and autonomic neuropathy (mean Ewing score: 5.73 +/- 2.34) were investigated. The gastrointestinal symptom scores were established by using the Talley dyspepsia questionnaire. The motor function of the digestive tract was tested in the esophagus, in the stomach, and in the ano-rectum by perfusion manometry. RESULTS: Manometric evaluation of the esophagus did not reveal significant abnormalities in the region of the upper sphincter in patients with diabetes mellitus. In contrast, diabetic patients had decreased peristaltic wave amplitude, prolonged duration, decreased wave propagation velocity, and increased number of simultaneous contractions in the esophageal body, and decreased lower esophageal sphincter pressures with prolonged relaxation compared to the age- and sex-matched controls. Symptom analysis showed correlations between reflux symptoms and LES relaxation times, and between dysphagia scores and esophageal body peristaltic wave duration, propagation velocity and the rate of simultaneous contractions. In the gastric antrum, frequent, and often severe, fasting motility disorders were observed, which had no correlation with dyspeptic symptoms. In the ano-rectal region the diabetic patients had a lower squeezing-resting pressure difference, and impaired fecal expulsive function. Motility disorders were simultaneously present at multiple parts of the gastrointestinal tract in 13/16 cases. CONCLUSIONS: In patients with type 1 diabetes mellitus and autonomic neuropathy gastrointestinal motility disorders were observed frequently, and in most of the cases simultaneously. While esophageal and ano-rectal symptoms correlated better with the manometric abnormalities, the lack of correlation between the impaired fasting gastric motility and dyspeptic symptoms shows that, on the basis of the clinical symptom analysis, the prevalence of such motor disorders could be underestimated. The early recognition of gastrointestinal motility disorders may be important for the better long-term management of patients with type 1 diabetes mellitus.

Adult↗
PubMed2003

Influence of sex and experimental protocol on the effect of maternal deprivation on rectal sensitivity to distension in the adult rat.

Neonatal maternal separation induces visceral hyperalgesia before and after stress in male rats. This study compares the effects on sensitivity to rectal distension in adult male and female rats, using two protocols of deprivation. Between postnatal days 1 and 14, maternal deprivation was performed for 2 h per day according to a protocol of type M (removal of all pups from home cage) or type P (separation of half of littermates). Visceral sensitivity was assessed at 12 weeks of age by the number of abdominal contractions induced by rectal distension before and after restraint stress. Calcitonin gene-related peptide (CGRP) was identified in the rectal wall by immunohistochemistry. In basal conditions, both separation protocols induced hyperalgesia, that was greater after type M than type P, and in females than in males for type P separation. Acute restraint stress induced hyperalgesia in control females only, and this effect was similarly enhanced by both type P and M separation. No difference was found between controls and deprived rats in rectal CGRP immunoreactivity which was greater in females and increased after rectal distension. These results indicate that long-term visceral hyperalgesia depends upon the type of maternal deprivation and that females are more sensitive than males.

Animals↗
PubMed2003

Oesophageal acid stimulation in humans: does it alter baroreflex function?

The aim of this study was to investigate if oesophagel acid stimulation (Bernstein test) had an influence on heart rate and blood prsure variability and baroreflex gain. We compared the cardiovascular responses in 10 patients with established gastro-esophageal reflux disease (Group 1) and 10 control subjects (Group 2) during esophageal saline and 0.1 mol/l hydrochloric acid instillation. Indices of heart rate and blood pressure variability and baroreflex gain (derived from linear spontaneous sequences and cross spectral analysis) were calculated. In Group 1 the standard deviation of RR intervals (SDRR: 46 ms vs 51 ms, p=0.030) and the root mean square of successive differences (RMSSD: 24 ms vs. 26 ms p=0.027) were significantly lower during acid infusions, than during saline. We found no significant difference in minimum, maximum and mean RR intervals and systolic blood pressures and in the percentage of RR intervals, which differed from adjacent cycles by more than 50 ms (PNN50). The power spectra of RR intervals in the high frequency band tended to be lower during acid infusion (p=0.055). There was no significant difference in blood pressure spectra, neither in low nor in high frequency band. In Group 2 there was no significant difference between any parameters measured during acid and saline. The baroreflex gain was not changed during the studied conditions in any group. Neither increased vagal tone, nor increased vagal variability occurred and the baroreflex gain was not altered during oesophageal acid simulation.

Adult↗
PubMed2002

Impaired accommodation of proximal stomach in patients with alcoholic liver cirrhosis.

BACKGROUND: Impaired gastric emptying has previously been detected by ultrasonography in cirrhotic patients, and the role of the type of meal has also been discussed. While these earlier studies dealt with the distal part of the stomach, the aim of our study was to examine the effects of three different types of meal on the proximal stomach in cirrhotic patients. METHODS: The proximal stomach was examined by ultrasonography in 15 healthy volunteers and in 21 alcoholic cirrhotic patients. The subjects received a liquid meal with a low calorie content and two different semisolid test meals with a low calorie content or high calorie and fat contents. The proximal gastric size was assessed by ultrasonography in a sagittal area and a frontal diameter. On the basis of assessment of the autonomic nervous function, the cirrhotic patients were divided into two groups: autonomic neuropathy positive and autonomic neuropathy negative. RESULTS: The postcibal gastric size immediately after ingestion of the liquid test meal was significantly lower in the cirrhotic patients than in the healthy controls. In the healthy volunteers, the measures of the proximal gastric size were significantly higher than in either group of cirrhotic patients at to, and at 10, 20 or 30 min after ingestion of a semisolid test meal with low calorie and fat contents. The proximal gastric sizes in the three groups of investigated subjects did not differ when the meal with high fat and calorie contents was tested. When the liquid meal was administered, the proximal gastric size was significantly lower in the cirrhotic patients with autonomic neuropathy. A significant intragroup difference was not observed when the semisolid meals were tested. CONCLUSIONS: This study reveals an impairment of the proximal stomach in alcoholic cirrhotic patients. The low calorie liquid meal distinguishes between the two groups of cirrhotic patients and healthy controls.

Autonomic Nervous System Diseases↗
PubMed2001

[Effect of continuous enteral feeding on pancreas exocrin function in rats].

The aim of this study was to examine the effects of continuous enteral feeding (CEF) on the exocrine pancreas in rats. Eight male Wistar rats were intrajejunally cannulated and CEF was started on postoperative day 6. In 10 control animals, laparotomy was followed by intragastric feeding (GF) with the same nutriment (Osmolite, Abbott, 254 mosm/l) from postoperative day 6. The daily discharge was 24 kcal in both groups. After five days of feeding, the pancreas was removed, its weight and its protein, DNA, trypsin and lipase contents were determined. The results revealed no significant difference in body weight loss between the two groups of animals, whereas the pancreas weight/body weight ratio was lower (p < 0.01) in the CEF group. The pancreatic protein, DNA, trypsin and lipase contents were decreased (p < 0.01) after CEF as compared with the values for the GF group.

Animals↗
PubMed2001

The spindle: a dynamic assembly of microtubules and motors.

In all eukaryotes, a microtubule-based structure known as the spindle is responsible for accurate chromosome segregation during cell division. Spindle assembly and function require localized regulation of microtubule dynamics and the activity of a variety of microtubule-based motor proteins. Recent work has begun to uncover the molecular mechanisms that underpin this process. Here we describe the structural and dynamic properties of the spindle, and introduce the current concepts regarding how a bipolar spindle is assembled and how it functions to segregate chromosomes.

Animals↗
PubMed2001

Continuous enteral feeding has an attenuating effect on the exocrine pancreas in rats.

INTRODUCTION: Recent clinical observations suggest that continuous enteral feeding (CEF) may exert a beneficial effect in the management of inflammatory pancreatic diseases. Its effects on the exocrine pancreas, however, remain only partially investigated. AIM: To examine the effects of CEF on the exocrine pancreas in rats. METHODOLOGY: Eight male Wistar rats were intrajejunally cannulated, and CEF was started on postoperative day 6. In 10 control animals, laparotomy was followed by intragastric feeding (GF) with the same nutriment (Osmolite, Abbott) from postoperative day 6. The daily discharge was 24 kcal in both groups. After 5 days of feeding, the pancreas was removed; its weight and its protein, DNA, trypsin, and lipase contents were determined; and the exocrine pancreas was also examined for structural changes. RESULTS: The results revealed no significant difference in body weight loss between the two groups of animals, whereas the pancreas weight/body weight ratio was lower (p < 0.01) in the CEF group. The pancreatic protein, DNA, and enzyme contents were decreased (p < 0.01) after CEF as compared with the values for the GF group. Histologic examinations demonstrated clear decreases in acinar size and in the zymogen content of the pancreas in the CEF animals. CONCLUSION: This study clearly indicates that CEF reduces the enzyme production of the pancreas.

Animals↗
PubMed2001

Cell motility: can Rho GTPases and microtubules point the way?

Migrating cells display a characteristic polarization of the actin cytoskeleton. Actin filaments polymerise in the protruding front of the cell whereas actin filament bundles contract in the cell body, which results in retraction of the cell's rear. The dynamic organization of the actin cytoskeleton provides the force for cell motility and is regulated by small GTPases of the Rho family, in particular Rac1, RhoA and Cdc42. Although the microtubule cytoskeleton is also polarized in a migrating cell, and microtubules are essential for the directed migration of many cell types, their role in cell motility is not well understood at a molecular level. Here, we discuss the potential molecular mechanisms for interplay of microtubules, actin and Rho GTPase signalling in cell polarization and motility. Recent evidence suggests that microtubules locally modulate the activity of Rho GTPases and, conversely, Rho GTPases might be responsible for the initial polarization of the microtubule cytoskeleton. Thus, microtubules might be part of a positive feedback mechanism that maintains the stable polarization of a directionally migrating cell.

Actins↗
PubMed2000

TPX2, A novel xenopus MAP involved in spindle pole organization.

TPX2, the targeting protein for Xenopus kinesin-like protein 2 (Xklp2), was identified as a microtubule-associated protein that mediates the binding of the COOH-terminal domain of Xklp2 to microtubules (Wittmann, T., H. Boleti, C. Antony, E. Karsenti, and I. Vernos. 1998. J. Cell Biol. 143:673-685). Here, we report the cloning and functional characterization of Xenopus TPX2. TPX2 is a novel, basic 82.4-kD protein that is phosphorylated during mitosis in a microtubule-dependent way. TPX2 is nuclear during interphase and becomes localized to spindle poles in mitosis. Spindle pole localization of TPX2 requires the activity of the dynein-dynactin complex. In late anaphase TPX2 becomes relocalized from the spindle poles to the midbody. TPX2 is highly homologous to a human protein of unknown function and thus defines a new family of vertebrate spindle pole components. We investigated the function of TPX2 using spindle assembly in Xenopus egg extracts. Immunodepletion of TPX2 from mitotic egg extracts resulted in bipolar structures with disintegrating poles and a decreased microtubule density. Addition of an excess of TPX2 to spindle assembly reactions gave rise to monopolar structures with abnormally enlarged poles. We conclude that, in addition to its function in targeting Xklp2 to microtubule minus ends during mitosis, TPX2 also participates in the organization of spindle poles.

Amino Acid Sequence↗
PubMed2000

Motor proteins regulate force interactions between microtubules and microfilaments in the axon.

It has long been known that microtubule depletion causes axons to retract in a microfilament-dependent manner, although it was not known whether these effects are the result of motor-generated forces on these cytoskeletal elements. Here we show that inhibition of the motor activity of cytoplasmic dynein causes the axon to retract in the presence of microtubules. This response is obliterated if microfilaments are depleted or if myosin motors are inhibited. We conclude that axonal retraction results from myosin-mediated forces on the microfilament array, and that these forces are counterbalanced or attenuated by dynein-mediated forces between the microfilament and microtubule arrays.

Actin Cytoskeleton↗
PubMed1999

[Helocobacter heilmannii (Gastrospirillum hominis)-associated gastritis: first reported cases in Hungary].

We found a tightly coiled bacterium, Helicobacter heilmannii that is distinct from Helicobacter pylori in the gastric mucosal biopsy of a 55-year-old man and a 30-year-old woman, both of whom had previous history of intermittent epigastric pain. The organisms were distributed in the antral mucosa, which was endoscopically interpreted as demonstrating chronic gastritis in one case, and being normal in the other. Histologically, the affected mucosa presented a mild chronic gastritis without activity and a moderate chronic gastritis with marker activity, respectively. The bacteria seen on haematoxylin eosin stained slides were strongly Giemsa positive, and were also visualized with Warthin-Starry stain. They were negative with the anti-Helicobacter pylori immunohistochemistry, although a few spots of staining could represent some cross reaction. Electron microscopy revealed fragments of bacterium, with its characteristic spiral shape and length of 4-7 mm in the plane of the section. One of the patient was treated medically and the control examination revealed normal antral mucosa without spiral bacteria. Detection of these organisms may provide a new insight into the pathogenesis of human gastritis.

Adult↗
PubMed1999

[Effectiveness of pinaverium bromide therapy on colonic motility disorders in irritable bowel syndrome].

The special patterns of the slow wave activity in irrittable bowel syndrome by means of surface electromyography were examined and the effect of pinaverium bromide on the symptoms and on the colonic motility in this disease was estimated. Twenty two patients with irritable bowel syndrome and 7 healthy controls were selected to the study. The clinical symptoms were abdominal pain and bloating in all patients, constipation in 9, and diarrhoea in 6 cases. Surface electromyography was carried out before and on the 14th day of the treatment with pinaverium bromide (50 mg t. i. d). The colonic motility was analysed in a 2 hour fasting and a 2 hour postprandial period following a standard (800 kCal) meal. The slow wave frequency of 0.01-0.04 Hz were selected and analysed. The mean frequency of activity peaks (n/10 min) and power-index (area under curve, microV 10 min) were measured. For statistical analysis Student's t-test was applied. Electromyogram of patients with irritable bowel syndrome showed a significant increase of the measured colonic motility parameters both in fasting and postprandial states. Fourteen days of pinaverium bromide treatment was able to significantly reduce the intensity of the colonic motor activity. Administration of pinaverium bromide completely released in 6 and significantly improved the abdominal pain in other 12 patients, while the bloating disappeared in 12 and was significantly improved in 5 from 22 patients. Pinaverium bromide was able to normalise the stool frequency: the weekly number of stools was decreased from 16 to 7 in the patients complaining diarrhoea ant it was increased from 2 to 6 in the patients with constipation.

Calcium Channel Blockers↗
PubMed1998

Localization of the kinesin-like protein Xklp2 to spindle poles requires a leucine zipper, a microtubule-associated protein, and dynein.

Xklp2 is a plus end-directed Xenopus kinesin-like protein localized at spindle poles and required for centrosome separation during spindle assembly in Xenopus egg extracts. A glutathione-S-transferase fusion protein containing the COOH-terminal domain of Xklp2 (GST-Xklp2-Tail) was previously found to localize to spindle poles (Boleti, H., E. Karsenti, and I. Vernos. 1996. Cell. 84:49-59). Now, we have examined the mechanism of localization of GST-Xklp2-Tail. Immunofluorescence and electron microscopy showed that Xklp2 and GST-Xklp2-Tail localize specifically to the minus ends of spindle pole and aster microtubules in mitotic, but not in interphase, Xenopus egg extracts. We found that dimerization and a COOH-terminal leucine zipper are required for this localization: a single point mutation in the leucine zipper prevented targeting. The mechanism of localization is complex and two additional factors in mitotic egg extracts are required for the targeting of GST-Xklp2-Tail to microtubule minus ends: (a) a novel 100-kD microtubule-associated protein that we named TPX2 (Targeting protein for Xklp2) that mediates the binding of GST-Xklp2-Tail to microtubules and (b) the dynein-dynactin complex that is required for the accumulation of GST-Xklp2-Tail at microtubule minus ends. We propose two molecular mechanisms that could account for the localization of Xklp2 to microtubule minus ends.

Animals↗
PubMed1998

[Food allergy in patients with respiratory allergy. Diagnostic possibilities and problems].

UNLABELLED: In the past two years the authors examined 28 patients with abdominal complaints and allergic respiratory symptoms. Detailed internal, gastroenterological, allergological examinations were made. METHODS: 1 skin Prick-test (SPT) with inhalative and nutritive panel 2. measuring of food-specific (gliadin, alpha-lactalbumin beta-lactoglobulin, ovalbumin) IgG-antibody level detecting with ELISA method, 3. leukocyte migration inhibition (LMI) test against the same foodstuffs, 4. histological examination of the stomach and the duodenum especially for mucosal mastocytes (MMCs). RESULTS: 1. SPT was positive in 23/28 patients for inhalative, but in the 5 cases we did not identify any inhalative allergen. The SPT for the main foodstuffs were positive in 18 patients while in 3 other patients there was urtica only for the other antigens. 2. The food-specific IgG-antibody level was increased in 18/27 patients against one or more antigens. The SPTs and the antibody determination showed identity in 8/18 cases. 3. The LMI tests were positive against one or more main food-products in 23/27 cases. There was common positivity in respect of antigens (between LMI test and antibody identification) in 17 cases. Pathological immunological reactions were presented against the same main foodstuffs with at least two methods for flour in 11, for egg in 10 and for milk in 12 patients. Endoscopic examinations were performed in 27 cases. The number of the MMCs were increased in 22/27 patients. After a specific elimination diet open-food challenges were performed and they confirmed the results of the in vitro and in vivo examinations. CONCLUSION: It is common that the respiratory allergic symptoms in atopic patients accompanied with food allergy for the main foodstuffs caused not only more severe respiratory symptoms, but abdominal complaints too. In respect to the many positive LMI tests the late-type hypersensitivity have important pathogenetical role in it. This three methods together define well the main food-products, which can be antigens as well. The examination of the MMCs supports the local disturbance in the immunoregulatory system.

Adolescent↗
PubMed1998

[Drug therapy of gastroesophageal reflux (a prospective controlled clinical trial)].

One year follow up(1.5, 3, 6, 12 months) study was established to examine the role of several classes of drugs in the treatment of reflux disease in 40 patients on the basis of objective control parameters (pH-metry, endoscopy, histology). The therapy was initiated, respectively, the different stage of severity (Savary-Miller): in stage 0 sucralfate + domperidone, in stage I and II: ranitidine + domperidone and in stage III-IV omeprazole was introduced. Our results proved that sucralfate + domperidone is curative on reflux oesophagitis in stage 0 cases. In stage I sucralfate and domperidone were effective in 3 of 9 cases, ranitidine + domperidone was optimal in 5 of 9, and omeprazole was required in 1 of 9 patients. In stage II, ranitidine + domperidone was effective only in 4 of 11 patients, and the initial therapy was modified to omeprazole in 7 of 11 patients to find the optimal drug in this stage. In stage III and IV only omeprazole showed curative effect and the doses required were 20 mg in 8 of 13 and 40 mg in 5 of 13 patients. The complaints improved in 34 of 40 patients after 6 weeks treatment, while histological healing of reflux oesophagitis was observed in 12 of 40 cases. After 3 months the endoscopic healing rate was 28/40, but histological healing could be reached after 6 months of optimal treatment in 30 of 40 cases. We can conclude, that the optimal drug selection may result a rapid improvement of complaints, but endoscopic and histological regeneration of the oesophageal mucosa is more graduated with time. The healing process of the reflux oesophagitis requires 3 months. Proton pump inhibitor drugs have an enhanced role in the treatment of gastrooesophageal reflux disease, and our results proved that the efficient and safety treatment of mild form (stage II) of disease requires the administration of proton pump inhibitors.

Adult↗
PubMed1997

Purification and characterization of full-length mammalian poly(A) polymerase.

Bovine poly(A) polymerase was purified from overexpressing strains of Escherichia coli and from Spodoptera frugiperda Sf21 cells infected with a recombinant baculovirus. The E. coli-expressed enzyme had an apparent molecular mass of 85 kDa in SDS gels, as anticipated from the cDNA sequence. Poly(A) polymerase from insect cells consisted of several species with higher apparent molecular weights due to phosphorylation. The two preparations showed minor differences in their catalytic properties. The insect cell-expressed enzyme had a 5-fold higher Km for the primer in a nonspecific Mn(2+)-dependent polyadenylation reaction and a lower activity in specific AAUAAA-dependent polyadenylation and generated shorter poly(A) tails during the processive phase of polyadenylation. Both recombinant poly(A) polymerases stimulated 3'-cleavage of the SV40 late mRNA precursor. Neither preparation contained ATPase or poly(A) degrading activity. The enzyme polymerized adenosine 5'-O-(1-thiotriphosphate), SP-diastereomer, with inversion of configuration. Thus, poly(A) synthesis proceeds via an SN2-in-line mechanism without covalent intermediate.

Adenosine Triphosphate↗