Biomedical subjects

M Ebert

Publications and source records attributed to M Ebert.

At least 19 recordsLinked to original sources

PubMed1998

Prenatal stress alters brain biogenic amine levels in primates.

In this study, we assessed behavioral responses to social separation at 8 months of age and cerebrospinal fluid (CSF) concentrations of biogenic amines and metabolites at 8 and 18 months of age in 12 rhesus monkeys derived from either stressed or undisturbed pregnancies. Compared to controls from undisturbed pregnancies, prenatal stress-derived monkeys had higher concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), and 3,4-dihydroxyphenylacetic acid in CSF than controls. Norepinephrine and MHPG response to stress were both correlated between 8 and 18 months of age. There were few group differences in behavior during social separation; however, several behavioral differences between groups were found when monkeys were reunited with cage mates. Prenatally stressed monkeys spent more time clinging to their surrogates and exploring (including eating and drinking), while controls showed more locomotion and social play with their cage mates. Collectively, our findings suggest that chronic unpredictable psychological stress during pregnancy has long-lasting effects on noradrenergic and dopaminergic activity and behavior in the offspring of gestationally stressed primate mothers.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Overexpression of platelet-derived growth factor (PDGF) B chain and type beta PDGF receptor in human chronic pancreatitis.

Platelet-derived growth factors (PDGF) are mitogenic polypeptides that are involved in cellular proliferation and tissue repair. The expression of PDGFs and type beta PDGF receptor was examined in the normal human pancreas and in chronic pancreatitis, a fibrotic disease associated with fibroblastic proliferation, atrophy, and acinar cell dedifferentiation. In the normal human pancreas, PDGF A chain mRNA levels were relatively abundant, whereas PDGF B chain mRNA levels were not detected, and type beta PDGF receptor mRNA transcripts were present at low levels. In the normal pancreas, PDGF immunoreactivity was present in islet cells, whereas type beta PDGF receptor immunoreactivity was present in acinar cells. In chronic pancreatitis, PDGF A chain mRNA transcripts were also abundant, and 11 of 19 samples exhibited the PDGF B chain mRNA transcript. In addition, there was a significant increase in the mRNA levels of type beta PDGF receptor in the pancreatitis samples by comparison with the normal pancreas (P < 0.001). In chronic pancreatitis tissues, PDGF and type beta PDGF receptor immunoreactivity were present in acinar, ductal, islet, and endothelial cells, fibroblasts, and leukocytes. The concomitant overexpression of PDGFs and of the type beta PDGF receptor points to the existence of autocrine and paracrine PDGF-dependent loops in human chronic pancreatitis.

Blotting, Northern↗

PubMed1998

Effector T lymphocyte subsets in human pancreatic cancer: detection of CD8+CD18+ cells and CD8+CD103+ cells by multi-epitope imaging.

Pancreatic cancer is characterized by an increasing incidence and an extremely poor prognosis. It is resistant to most of the conventional treatment modalities. Histomorphologically, it presents with a strong desmoplastic reaction around cancer cells, and lymphocytes are typically localized as aggregates in the fibrotic interstitial tissue. Using the method of multi-epitope imaging with fluorochrome-tagged specific MoAbs which allows the simultaneous localization and characterization of T cells in tissues, we studied phenotypes and distribution of tumour-infiltrating lymphocytes (TIL) in pancreatic cancer. CD3+ T cells comprised up to 90% of the tumour-infiltrating cells which were either CD4+ or CD8+, most of them being memory cells (CD45RO+). In decreasing order of frequency, T lymphocytes carried the markers for CD45RO, CD18, CD103 and TCR gammadelta. Very few natural killer cells (CD56+) were observed. Twenty percent of CD8+ were labelled with CD103. These CD8+CD103+ T cells, analogous to the gut intraepithelial lymphocytes (IEL), were found in the fibrous interstitial tissue. Furthermore, an inverse correlation was found between the expression of CD18, the beta2-integrin, which mediates adhesion of activated lymphocytes, and CD45RO in the CD8+ subset of TIL (P = 0.046). In conclusion, phenotyping of T lymphocytes in pancreatic cancer raises the possibility that pancreatic cancer cells develop several strategies to escape the T cell-induced cytolysis by (i) the aggregation of cytotoxic CD8+CD103+ T cells in the fibrous tissue distant from the tumour cells, and (ii) the presence of CD18-bearing cells which lack the expression of the activation marker CD45RO.

Adolescent↗

PubMed1998

T-cell receptor Valpha gene expression of infiltrating T cells in pancreatic cancer.

BACKGROUND: T lymphocytes play a central role in the immune response to cancer, with specific T-cell reactivity provided by the T-cell receptor (TCR) alphabeta-chain heterodimer. Whereas human pancreatic adenocarcinoma is characterized by a massive infiltration of T lymphocytes, to date no analysis of the TCR Valpha-gene expression of the tumor-infiltrating lymphocytes in pancreatic cancer has been performed. METHODS: Using reverse transcriptase polymerase chain reaction (RT-PCR) followed by dot blot hybridization, we determined the TCR alpha-chain repertoire at the mRNA level in pancreatic carcinoma and compared our findings with the TCR Valpha repertoire in the normal pancreas and chronic pancreatitis. RESULTS: A heterogeneous lowly restricted TCR Valpha repertoire was observed in pancreatic carcinomas, different from the TCR Valpha repertoire in chronic pancreatitis. CONCLUSIONS: Pancreas-infiltrating T cells show a distinct TCR Valpha gene expression profile in normal pancreas, chronic pancreatitis, and pancreatic cancer.

Adenocarcinoma↗

PubMed1998

Monte Carlo simulation of electron cones used in electron beam therapy.

A Siemens Mevatron KV2 accelerator installed at the Royal Adelaide Hospital employs cylindrical solid-walled electron cones for some electron collimation. The cones being used at present result in treatment fields that do not always conform with the International Electrotechnical Commission (IEC) Standards (particularly at high energies). The aim of this project was to simulate the existing cones using Monte Carlo methods in order to evaluate potential cone modifications required to overcome the field irregularities. Simulations were performed using the EGS4 (Electron Gamma Shower version 4, distribution II) Monte Carlo code installed on a DEC Alpha workstation at the University of South Australia. To rigorously simulate the existing electron cones it was necessary to also simulate various components within the treatment head of the linear accelerator. Results of simulations for existing cones were found to be consistent with experimental data. (obtained from Royal Adelaide Hospital beam quality assurance measurements). Two proposed changes to the cones were then simulated and the effects of these alterations were assessed. This study has shown how treatment head simulation techniques can be used to assess the changes in dose distribution that result from alterations to the treatment head and accessories. Within practical engineering constraints modifications to an existing electron collimation system were proposed and theoretically evaluated.

Biophysical Phenomena↗

PubMed1997

Inhibition of elastase improves myocardial function after repetitive ischaemia and myocardial infarction in the rat heart.

We investigated the potential of inhibition of elastase, a granulocyte-derived proteolytic enzyme, in ameliorating the effects of myocardial stunning caused by repetitive ischaemia (RI) and myocardial infarction (MI) for the first time in an in situ, perfused, rat heart model. The effects of the elastase-inhibitors Elafin (EL, 10 mg/kg/h) and ICI 200,880 (ICI,5 mg/kg/h) on myocardial blood flow (MBF, H2 clearance), regional myocardial function (FT, pulsed doppler) and neutrophil extravasation (myocardial myeloperoxidase activity, MPO) were investigated in RI (5x10 min ligature of the anterior descending ramus (LAD), 5x20 min reperfusion) and MI (50 min LAD ligature, 60 min reperfusion). Under control conditions, MBF and FT were significantly reduced and MPO was significantly increased after RI (n=8) and MI (n=8) in the ischaemic area compared with baseline. Pretreatment with EL (n=7) or ICI (n=7) did not improve MBF significantly and did not influence the successive attenuation of peak values of reactive hyperaemia. However, both EL and ICI significantly improved FT and significantly reduced MPO after RI and MI compared with control conditions. Additionally, both the area at risk and MI size were reduced significantly by both inhibitors. These results demonstrate that elastase inhibitors significantly improve the reduction of FT both in myocardial stunning and in myocardial infarction in the rat without significant improvement of MBF. It is concluded that elastase inhibitors exert a cardioprotective effect against reperfusion injury, probably by inhibition of leukocyte extravasation as indicated by the decrease in MPO activity.

Animals↗

PubMed1997

Absence of K-ras mutations in the pancreatic parenchyma of patients with chronic pancreatitis.

BACKGROUND: Human pancreatic cancers exhibit a high frequency of K-ras mutations. METHODS: In this study we used oligonucleotide specific hybridization to compare the frequency of K-ras mutations in genomic DNA samples prepared from 21 normal pancreatic tissues, 26 chronic pancreatitis tissues, and 24 pancreatic cancers. RESULTS: None of the DNA samples from normal or chronic pancreatitis tissues exhibited a K-ras mutation at codons 12 or 13 of K-ras. In contrast, 17 of 24 DNA pancreatic cancers harbored a K-ras mutation. Validity of the methodology was confirmed by genotyping 7 human pancreatic cancer cell lines. Analysis of focal areas of proliferation from 5 chronic pancreatitis and 5 pancreatic cancer samples processed by selective ultraviolet radiation fractionation (SURF), a procedure used to enrich DNA isolation from foci of proliferating cells, revealed complete concordance with total genomic DNA analysis. CONCLUSIONS: These findings indicate that the pancreatic parenchyma in patients with chronic pancreatitis most frequently does not possess a K-ras mutation.

Adolescent↗

PubMed1997

[The helium-3 MRT of pulmonary ventilation: the initial clinical applications].

PURPOSE: of the study is the visualisation of normal pulmonary ventilation in healthy volunteers and the evaluation of abnormalities in patients with different lung diseases using 3He magnetic resonance imaging (3He-MRI). MATERIAL AND METHODS: Hyperpolarized 3He gas (V = 300 ml, p = 3 x 10(5) Pa, polarised to 35-45% by optical pumping, provided in special glass cells) was inhaled by eight healthy volunteers and ten patients with different lung diseases. A 3D FLASH sequence (TR = 11.8 ms; TE = 5 ms; matrix 144 x 256, FOV 350 mm, section thickness 7-10 mm, coronal orientation) was performed in a single breath-hold (22-42 s). Clinical and radiological examinations were available for correlation. RESULTS: The studies were successfully carried out in 8/8 volunteers and in 8/10 patients. The central airways were constantly visualised with intermediate to high signal intensity. The lung parenchyma of volunteers with normal ventilatory function showed rather homogeneous intermediate to high signal, whereas patients with chronic obstructive lung disease and/or pneumonia presented severe signal inhomogeneities. Space-occupying lesions and pleural effusion caused large areas with little or no signal. The represented the lesion and adjacent ventilatory disturbances whose extent had not been presumed from chest x-ray or CT. The spatial resolution was higher than in ventilation scintigraphy. CONCLUSION: 3He MRI is a promising new modality for the assessment of pulmonary ventilation and its anomalies.

Administration, Inhalation↗

PubMed1997

Hyperpolarized gases--a new type of MR contrast agents?

The nuclear spin polarization of noble gases can be strongly enhanced by laser optical pumping followed by electron-nuclear polarization transfer. Direct optical pumping of metastable 3He atoms has been shown to produce enormous polarization in the order of 0.4-0.6. This is about 10(5) times greater than the polarization of water protons at thermal equilibrium used at conventional MR imaging. We demonstrate that hyperpolarized 3He gas can be applied to nuclear MR imaging of human organs with air-filled spaces. In vivo 3He MR experiments were performed in a whole-body MR scanner with a superconducting magnet ramped down to 0.8 T and at 1.5 T using a double resonant Helmholtz coil operating at 63.6 and 48.6 MHz for 1H and 3He, respectively. Anatomical details of the lungs of a volunteer were visualized with the FLASH technique demonstrating the potential of the method for fast imaging of airways in the human body and for pulmonary ventilation studies.

Contrast Media↗

PubMed1997

Optimisation in radiotherapy. II: Programmed and inversion optimisation algorithms.

This is the second article in a three part examination of optimisation in radiotherapy. The previous article established the bases of optimisation in radiotherapy, and the formulation of the optimisation problem. This paper outlines several algorithms that have been used in radiotherapy, for searching for the best irradiation strategy within the full set of possible strategies. Two principle classes of algorithm are considered--those associated with mathematical programming which employ specific search techniques, linear programming-type searches or artificial intelligence--and those which seek to perform a numerical inversion of the optimisation problem, finishing with deterministic iterative inversion.

Algorithms↗

PubMed1997

Optimisation in radiotherapy. III: Stochastic optimisation algorithms and conclusions.

This is the final article in a three part examination of optimisation in radiotherapy. Previous articles have established the bases and form of the radiotherapy optimisation problem, and examined certain types of optimisation algorithm, namely, those which perform some form of ordered search of the solution space (mathematical programming), and those which attempt to find the closest feasible solution to the inverse planning problem (deterministic inversion). The current paper examines algorithms which search the space of possible irradiation strategies by stochastic methods. The resulting iterative search methods move about the solution space by sampling random variates, which gradually become more constricted as the algorithm converges upon the optimal solution. This paper also discusses the implementation of optimisation in radiotherapy practice.

Algorithms↗

PubMed1996

Nuclear magnetic resonance imaging with hyperpolarised helium-3.

BACKGROUND: Magnetic resonance imaging (MRI) relies on magnetisation of hydrogen nuclei (protons) of water molecules in tissue as source of the signal. This technique has been valuable for studying tissues that contain significant amounts of water, but biological settings with low proton content, notably the lungs, are difficult to image. We report use of spin-polarised helium-3 for lung MRI. METHODS: A volunteer inhaled hyperpolarised 3He to fill the lungs, which were imaged with a conventional MRI detector assembly. The nuclear spin polarisation of helium, and other noble gases, can be greatly enhanced by laser optical pumping and is about 10(5) times larger than the polarisation of water protons. This enormous gain in polarisation easily overcomes the loss in signal due to the lower density of the gas. FINDINGS: The in-vivo experiment was done in a whole-body MRI scanner. The 3He image showed clear demarcation of the lung against diaphragm, heart, chest wall, and blood vessels (which gave no signal). The signal intensity within the air spaces was greatest in lung regions that are preferentially ventilated in the supine position; less well ventilated areas, such as the apices, showed a weaker signal. INTERPRETATION: MRI with hyperpolarised 3He gas could be an alternative to established nuclear medicine methods. The ability to image air spaces offers the possibility of investigating physiological and pathophysiological processes in pulmonary ventilation and differences in its regional distribution.

Adult↗

PubMed1996

Nuclear magnetic resonance imaging of airways in humans with use of hyperpolarized 3He.

The nuclear spin polarization of noble gases can be enhanced strongly by laser optical pumping followed by electron-nuclear polarization transfer. Direct optical pumping of metastable 3He atoms has been shown to produce enormous polarization on the order of 0.4-0.6. This is about 10(5) times larger than the polarization of water protons at thermal equilibrium used in conventional MRI. We demonstrate that hyperpolarized 3He gas can be applied to nuclear magnetic resonance imaging of organs with air-filled spaces in humans. In vivo 3He MR experiments were performed in a whole-body MR scanner with a superconducting magnet ramped down to 0.8 T. Anatomical details of the upper respiratory tract and of the lungs of a volunteer were visualized with the FLASH technique demonstrating the potential of the method for fast imaging of airways in the human body and for pulmonary ventilation studies.

Adult↗

PubMed1995

Induction of platelet-derived growth factor A and B chains and over-expression of their receptors in human pancreatic cancer.

Expression of platelet-derived growth factor (PDGF) and PDGF receptors was examined in cultured human pancreatic cancer cells, in the normal human pancreas and in pancreatic adenocarcinomas. mRNA transcripts encoding PDGF A and B chains, and PDGF receptor beta (PDGFR beta) were present in PANC-I and HPAF human pancreatic cancer cells. Transforming growth factor beta I (TGF-beta I), but not PDGF-AA or -BB, enhanced PDGF A and B chain mRNA levels in both cell lines. In the normal human pancreas PDGF A chain mRNA levels were relatively abundant, whereas PDGF B chain mRNA levels were not detected and PDGF receptor alpha (PDGFR alpha) and beta mRNA transcripts were present at low levels. PDGF immunoreactivity was present in islet cells, and PDGFR alpha was present in acinar cells, whereas PDGFR beta was present in acinar cells and in the connective tissue. In the pancreatic cancers, PDGF A chain mRNA transcripts were also abundant, and 6 of 13 samples exhibited the PDGF B chain mRNA transcript. In addition, there was a 7-fold increase in the levels of PDGFR alpha and PDGFR beta in the cancer samples by comparison with the normal pancreas. By immunohistochemistry, PDGF and both PDGF receptors were present in the cancer cells, and PDGFR beta was abundant in fibroblasts and endothelial cells within the connective tissue.

Base Sequence↗

PubMed1995

Differential distribution of human epidermal growth factor receptor family in acute pancreatitis.

Using northern blot analysis and immunohistochemistry, we assessed the expression and distribution of human epidermal growth factor receptor-1 (HER-1), HER-2, and HER-3 in pancreatic tissues obtained from patients with acute pancreatitis (AP). Overall, HER-1, HER-2, and HER-3 mRNA levels were similar in the normal pancreas and in the pancreas of AP patients. However, three patients exhibited a significant increase in HER-1 mRNA levels. Furthermore, the distribution of the receptors differed with respect to the various cell types in the human pancreas. In the normal pancreas, moderate HER-1 and strong HER-3 immunoreactivity was present predominantly in the cytoplasm of acinar cells and to a lesser extent in the ductal cells, whereas strong HER-2 immunoreactivity was present in the islet cells. In the AP tissues, there was a marked increase in HER-1 immunoreactivity in acinar and ductal-like cells, whereas HER-3 immunoreactivity was less prominent in acini and increased in ductal-like cells. HER-2 immunoreactivity was again mainly evident in islet cells, but was also present in the ductal-like cells. These findings indicate that there is altered distribution of HERs in the pancreas following AP and raise the possibility that HERs may be involved in the process of pancreatic regeneration during recovery from AP.

Acute Disease↗

PubMed1995

Diagnosis of pancreatic cancer by 2[18F]-fluoro-2-deoxy-D-glucose positron emission tomography.

The detection of pancreatic cancer or the discrimination between pancreatic cancer and chronic pancreatitis remains an important diagnostic problem. The increased glucose metabolism in malignant tumours formed the basis for this investigation, which focused on the role of positron emission tomography (PET) with 2[18F]-fluoro-2-deoxy-D-glucose (FDG) in the detection of pancreatic cancer and its differentiation from chronic pancreatitis. Eighty patients admitted for elective pancreatic surgery received preoperatively 250-350 mBq FDG intravenously and emission scans were recorded 45 minutes later. Intense focal activity in the pancreatic region was taken at the time of scanning as showing the presence of pancreatic cancer. The presence of cancer was later confirmed by histological examination of the surgical specimens and histological findings were compared with the preoperative PET results. Forty one patients with pancreatic cancer (group I: n = 42) had a focally increased FDG uptake in the pancreatic region. Two patients with a periampullary carcinoma (group II: n = 6) failed to develop FDG accumulation. In 28 patients with chronic pancreatitis (group III: n = 32) no FDG accumulation occurred. Overall sensitivity and specificity of PET for malignancy (group I + II) were 94% (45 of 48) and 88% (28 of 32), respectively. The standard uptake value of the patients with pancreatic carcinoma was significantly higher than in patients with chronic pancreatitis (3.09 (2.18) v 0.87 (0.56); p < 0.001; median (interquartile range)). These findings show that FDG-PET represents a new and non-invasive diagnostic procedure for the diagnosis of pancreatic cancer and to differentiate pancreatic cancer from chronic pancreatitis. However, the diagnostic potential of this technique requires further evaluation.

Adult↗

PubMed1995

[Chronic pancreatitis with inflammatory enlargement of the pancreatic head].

A number of patients with chronic pancreatitis develop an inflammatory enlargement of the head of the pancreas leading to complications such as common bile duct, duodenal, pancreatic duct, and/or vascular obstruction. The duodenum preserving pancreatic head resection has been developed to treat these lesions and to avoid a Whipple procedure in chronic pancreatitis. Between 1972 and 1992 280 patients (231 male, 49 female, mean age 44, range 22-76 years) underwent a duodenum preserving pancreatic head resection for chronic pancreatitis. The indication to operate was a cholestases syndrome in 50% of the patients, a duodenal compression in 36% and an obstruction of the portal vein in 16% of the patients. 94% suffered from pain, 53% had recurrent severe pain attacks and 72% had daily pain. Hospital mortality was 1.1% (3/280). Pancreatic fistula, leakage of pancreatic anastomosis and postoperative bleeding occurred in 4.6%, 1.8% and 3.2% of the patients, respectively. A relaparotomy needed 16 patients (5.7%). With respect to glucose tolerance in the early postoperative period 88% of the patients, showed no change in comparison with the preoperative glucose tolerance analysis. In a long-term follow-up (mean follow-up time was 3.7 years (3 months to 18 years)) 219 patients were included. The late mortality within the follow-up period was 5.0% (11/219). 90% of the patients had no or rare pain in the long-term follow-up. 63% of the patients were full rehabilitated professionally. The duodenum preserving pancreatic head resection represents a new standard procedure which solves most surgical problems in chronic pancreatitis. It does not lead to diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Coexpression of the c-met proto-oncogene and hepatocyte growth factor in human pancreatic cancer.

The c-met proto-oncogene encodes a transmembrane tyrosine kinase receptor (MET) that has the capacity to modulate cell proliferation and differentiation; it is activated by the hepatocyte growth factor. Using a highly specific anti-MET antibody we found mild MET immunoreactivity in acinar, ductal, and islet cells in the normal human pancreas and intense MET immunoreactivity in many of the duct-like cancer cells in 14 of 16 human pancreatic adenocarcinomas. Intense MET immunoreactivity was also evident in the ductal cells in regions adjacent to the cancer cells. Northern blot analysis of total RNA revealed that, by comparison with the normal pancreas, pancreatic cancers exhibited a 7-fold (P < 0.01) increase in c-met mRNA levels. Hepatocyte growth factor mRNA levels were increased 10-fold (P < 0.05) in the same cancers. The concomitant over-expression of c-met and hepatocyte growth factor in human pancreatic cancers suggests that there is excessive activation of c-met-dependent signaling pathways that may contribute to pancreatic cancer cell growth in vivo.

Adolescent↗