Biomedical subjects

R Thul

Publications and source records attributed to R Thul.

8 recordsLinked to original sources

PubMed2006

Frequency of elemental events of intracellular Ca(2+) dynamics.

The dynamics of intracellular Ca(2+) is driven by random events called Ca(2+) puffs, in which Ca(2+) is liberated from intracellular stores. We show that the emergence of Ca(2+) puffs can be mapped to an escape process. The mean first passage times that correspond to the stochastic fraction of puff periods are computed from a novel master equation and two Fokker-Planck equations. Our results demonstrate that the mathematical modeling of Ca(2+) puffs has to account for the discrete character of the Ca(2+) release sites and does not permit a continuous description of the number of open channels.

Calcium↗

PubMed2005

Reactive clusters on a membrane.

We investigate the reaction dynamics of diffusive molecules with immobile binding partners. The fixed reactants build clusters that are comprised of just a few tens of molecules, which leads to small cluster sizes. These molecules participate in the reaction only if they are activated. The dynamics of activation is mapped to a time-dependent size of an active region within the cluster. We focus on the deterministic description of the dynamics of a single cluster. The spatial setup accounts for one of the most important determinants of the dynamics of a cluster, i.e. diffusional transport of reaction partners towards or away from the active region of the cluster. We provide numerical and analytical evidence that diffusion influences decisively the dynamic regimes of the reactions. The application of our methods to intracellular Ca2+ dynamics shows that large local concentrations saturate the Ca2+ feedback to the channel state control. It eliminates oscillations depending on this feedback.

Animals↗

PubMed2004

Stability of membrane bound reactions.

We present a novel approach to the dynamics of reactions of diffusing chemical species with species fixed in space, e.g., by binding to a membrane. The nondiffusing reaction partners are clustered in areas with a diameter smaller than the diffusion length of the diffusing partner. The activated fraction of the fixed species determines the size of an active subregion of the cluster. Linear stability analysis reveals that diffusion is one of the major determinants of the stability of the dynamics. We illustrate the model concept with Ca2+ dynamics in living cells, which has release channels as fixed reaction partners. Our results suggest that spatial and temporal structures in intracellular Ca2+ dynamics are caused by fluctuations due to the small number of channels per cluster.

Calcium↗

PubMed2004

Release currents of IP(3) receptor channel clusters and concentration profiles.

We simulate currents and concentration profiles generated by Ca(2+) release from the endoplasmic reticulum (ER) to the cytosol through IP(3) receptor channel clusters. Clusters are described as conducting pores in the lumenal membrane with a diameter from 6 nm to 36 nm. The endoplasmic reticulum is modeled as a disc with a radius of 1-12 microm and an inner height of 28 nm. We adapt the dependence of the currents on the trans Ca(2+) concentration (intralumenal) measured in lipid bilayer experiments to the cellular geometry. Simulated currents are compared with signal mass measurements in Xenopus oocytes. We find that release currents depend linearly on the concentration of free Ca(2+) in the lumen. The release current is approximately proportional to the square root of the number of open channels in a cluster. Cytosolic concentrations at the location of the cluster range from 25 microM to 170 microM. Concentration increase due to puffs in a distance of a few micrometers from the puff site is found to be in the nanomolar range. Release currents decay biexponentially with timescales of <1 s and a few seconds. Concentration profiles decay with timescales of 0.125-0.250 s upon termination of release.

Animals↗

PubMed2003

[Heterotopic gastric pancreas: a rare cause of abdominal complaints].

Heterotopic pancreas is an uncommon cause of gastrointestinal complaints such as epigastric pain, nausea, vomiting, and upper gastrointestinal bleeding. Despite the development of modern diagnostic procedures, it is still difficult to differentiate heterotopic pancreatic tissue from other benign or malignant gastric tumors. Local excision of the gastric wall is regarded as the diagnostic and therapeutic procedure of choice. We present two cases and an overview of the literature.

Choristoma↗

PubMed1998

EUS-guided, fine-needle aspiration biopsy using a new mechanical scanning puncture echoendoscope.

BACKGROUND: A new mechanical sector scanning echoendoscope designed for EUS-guided, fine-needle aspiration biopsy (FNAB) was prospectively evaluated. The technical feasibility, safety, and histocytologic FNAB results are reported. METHODS: Eighty-six patients underwent 106 FNAB procedures. The new echoendoscope has a 2.8 mm accessory channel and an elevator. Target sites: pancreas 58, lymph nodes 43, and miscellaneous lesions 5. Lesions were punctured with a 0.7 mm needle and submitted for cytologic and histologic examination. Definitive diagnosis was by surgery or clinical follow-up. RESULTS: The wide scanning field (250 degrees) enabled easy sonographic orientation for FNAB. Longitudinal needle visibility was "good" in 93% and 71% of transesophageal and transgastric procedures, respectively, but were compromised during most transduodenal procedures. Needle penetration of indurated pancreatic lesions failed in two patients, and in four additional patients pancreatic sampling succeeded only after a second attempt using an automated spring-loaded device. The mean number of passes was three. Ten percent of FNAB specimens were "inadequate"; excluding these, the diagnostic accuracy rate was 97%; sensitivity for malignancy was 88.5% and specificity was 100%. CONCLUSION: EUS-guided FNAB is feasible, safe, and accurate using the new mechanical puncture echoendoscope. Needle visibility needs to be improved, particularly for transduodenal FNAB.

Adult↗

PubMed1998

Endoscopic ultrasound-guided, 18-gauge, fine needle aspiration biopsy of the pancreas using a 2.8 mm channel convex array echoendoscope.

BACKGROUND: Previous studies have reported on endoscopic ultrasound-guided, fine needle aspiration biopsy using 22- to 25-gauge needles. We evaluated the histologic and cytologic yield of endoscopic ultrasound-guided, fine needle aspiration biopsy of the pancreas using an 18-gauge, Menghini-type core needle. METHODS: Fine needle aspiration biopsy was performed in conjunction with a prototype 2.8 mm channel convex array echoendoscope. The core specimen was placed in formalin for cell block, and residual material was expelled on slides for cytology. Definitive diagnosis was established by surgery or clinical follow-up. RESULTS: Of 45 patients who underwent fine needle aspiration biopsy, the needle failed to penetrate indurated pancreatic lesions in five. An average of 2.6 passes were performed in the remaining patients. Sufficient material for a histologic and/or cytologic diagnosis was obtained in 40 patients (histologic and cytologic yield of 68% and 75%, respectively). Combining the results of histology and cytology, the sensitivity and specificity for detection of malignancy was 76% and 100%, respectively. Histology confirmed the cytologic findings in 35 patients, providing additional tissue specific information. In three cases histology established a diagnosis of malignancy where cytology was not conclusively malignant. However, in three cases of surgically confirmed malignancy histology failed to detect malignancy, whereas cytology showed suspicious or malignant cells. The sensitivity of histology and cytology alone in detecting malignancy was 53% and 70%, respectively. Mild pancreatitis occurred after pancreatic fine needle aspiration biopsy in one patient. CONCLUSION: Core specimens for histology can be safely obtained using an 18-gauge needle. Histology provides tissue-specific information that complements cytology, but histology is less sensitive than cytology in detecting malignancy.

Adenocarcinoma↗

PubMedDate not supplied

Analysis of K-ras mutations in pancreatic tissue after fine needle aspirates.

The majority of pancreatic carcinomas contain a mutation at codon 12 of the K-ras oncogene. We have analysed 87 samples from 76 patients who underwent surgery because of different pancreatic diseases to evaluate whether the detection of K-ras mutations may be helpful to discriminate between chronic inflammation and neoplastic growth. Mutation analysis was performed using a semi-nested PCR followed by a selective restriction enzyme digestion. The correlation of clinical follow ups with the results of the molecular analysis was performed from 47 patients. K-ras mutations were detected in 50% of adenocarcinomas and no point mutation was found in normal pancreatic tissue and in tumor tissue from entities other than pancreas. Otherwise, K-ras mutations were detected in tissue samples from two patients with chronic pancreatitis, and one patient was found to have an adenocarcinoma after additional clinical investigation. Further studies especially follow ups will be helpful to get a better insight into the pathogenesis of pancreatic tumors and may be useful as an early diagnostic test.

Adenocarcinoma↗