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R Reiter

Publications and source records attributed to R Reiter.

At least 19 recordsLinked to original sources
PubMed2006

In vitro genotoxicity and cytotoxicity of benzalkonium chloride.

Benzalkonium chloride (BAC) acts as a preservative in numerous nasal preparations. Possible genotoxic and cytotoxic effects of BAC in human respiratory epithelial BEAS-2B cells should be investigated in vitro. Cell cultures were exposed for 2h to BAC in concentrations ranging from 0.002% to 0.05%. Methyl methanesulfonate served as positive control, PBS as negative control. The tail moment of single-cell gel-electrophoresis (SCGE) was used to assess BAC-induced DNA damage. Cell viability was measured by trypan blue dye exclusion staining. Additionally, the critical micellar concentration (CMC) of BAC in PBS was detected. The tail moment increased dose dependently with the maximum value at 0.02%, and declined for higher concentrations. Nearly all cells died at low BAC concentrations up to 0.01%. Above this concentration cell viability increased. The CMC of BAC in PBS was estimated to be 0.02%. BAC caused relevant DNA changes in respiratory epithelial cells in vitro at concentrations commonly employed in commercially available nasal preparations. Some of the exposed cells survived. In further studies it could be considered to look whether these cells would still be able to proliferate and possibly fix the damage that they have possibly accumulated into an actual mutation using for example the induction of micronuclei.

Benzalkonium Compounds↗
PubMed2006

Prognostic significance of expression patterns of c-erbB-2, p53, p16INK4A, p27KIP1, cyclin D1 and epidermal growth factor receptor in oesophageal adenocarcinoma: a tissue microarray study.

AIMS: To correlate immunohistochemical expression patterns and prognosis in oesophageal adenocarcinoma. METHODS: The expression of c-erbB-2, p53, p16INK4A, p27KIP1, cyclin D1 and epidermal growth factor receptor (EGFR) was studied in a series of 137 primarily resected oesophageal adenocarcinoma samples. The expression analysis on protein level was performed on routine paraffin wax-embedded material, with immunohistochemical staining of the samples, assembled on a tissue microarray. The results were correlated with clinicopathological features (pT, pN and G) and survival. RESULTS: 22 (16%) tumours showed an overexpression of the c-erbB-2 oncoprotein. Expression of EGFR was observed in 72 (55%) cases, accumulation of p53 in 68 (52%) cases and of cyclin D1 in 102 (77%) cases. Loss of p16INK4A expression was observed in 101 (76%) cases and low expression of p27KIP1 in 91 (71%) cases. Expression of these proteins did not correlate with tumour stage, grade, Lauren's or World Health Organization classification or lymph node status. On univariate survival analysis, more advanced tumour stage (p = 0.002), lymph node involvement (p = 0.003), high tumour grade (p = 0.017) and lack of EGFR expression (p = 0.034) were found to be associated with poorer survival. On multiple regression analysis, only tumour stage (p = 0.03) and lymph node involvement (p = 0.004) were shown to have an association with the survival of the patient. CONCLUSION: The immunohistochemical expression of c-erbB-2 oncoprotein, cylin D1, p16INK4A, p27KIP1, p53 and EGFR in most oesophageal adenocarcinomas suggests their implication in the pathogenesis of this entity. None of the molecular markers assessed, however, was of prognostic value. Identification of any marker superior to or even approaching the prognostic value of conventional histopathological markers (pT and pN) was therefore not possible.

Adenocarcinoma↗
PubMed2005

[Disability-adjusted life years: an instrument for defining public health priorities?].

BACKGROUND: The objective of this paper is the study of a health indicator allowing surveillance and evaluation of the overall health of the Paris population, and providing information to help prioritize possible choices among preventive and curative actions. Moreover, comparison between results obtained for Paris with a global health indicator, "Disability-adjusted life years" (DALYs) and available bibliographical data will enable clarifying some points about summary measures of health. METHODS: The method used is that of the Global Burden of Disease. It allows a ranking of diseases using an indicator called DALYs. This indicator integrates mortality and morbidity components by summing expected years of life lost due to premature mortality and calculated years of healthy life lost. DALYs were calculated using local mortality data and published regional disabilities tables from the World Health Organisation (WHO). RESULTS: There were a total of 242 061 DALYs for Paris for the year 1999. The six leading specific causes are: alcoholic psychosis and dependence (accounting for 6.5% of the total), lung cancers (5.7%), ischaemic hearth disease (4.8%), depression (4.4%), dementias (4.2%), and arthritis (3.9%). Men contributed the majority of DALYs for the first three. For four of the six leading causes, the majority of DALYs came from years lived with disability, rather than mortality. Only for lung cancer and ischaemic hearth disease was the majority of DALYs from years of life lost by mortality. CONCLUSION: The results for Paris are used to illustrate how DALYs can illuminate debates about public health priorities. Such data can inform the population about health condition and provide decision makers with global health indicators. The next step will be to estimate the DALYs from local morbidity data when available, and compare these results to those based on the World Health Organisation tables, which are not sensitive to local results other than those due to mortality. Future steps include further evaluation and development of this method for surveillance, assessment and evaluation of public health actions. However, some of the results obtained with this indicator underline the limits of this kind of analysis.

Adolescent↗
PubMed2003

Intima media thickness of carotid arteries is reduced in heterozygous carriers of the Gly972Arg variant in the insulin receptor substrate-1 gene.

BACKGROUND: The Gly972Arg mutation in the IRS-1 gene has been found to be associated with insulin resistance and type II diabetes. A recently published study described an association between the Arg allele and an increased risk for coronary artery disease. In the present study we asked whether the presence of the codon 972 mutation in the IRS-1 gene is associated with higher IMT values of the carotid arteries. MATERIALS AND METHODS: To address this question, genotypes of the codon 972 polymorphism were determined in 1018 healthy unrelated individuals aged 40-65 years. Three homozygous carriers of the mutation were excluded for statistical analysis. In all subjects, intima media thickness (IMT) and B-scores of carotid arteries as well as a large number of metabolic parameters were determined. RESULTS: Heterozygous carriers of the Arg972 allele exhibited significantly lower IMT and B-score values than noncarriers. Total cholesterol, LDL-cholesterol and serum levels of apolipoprotein B were significantly lower in the carriers. Furthermore, a significant interaction between Gly972Arg-carrier status and mean daytime 24-h systolic blood pressure with regard to IMT could be observed; carriers with a systolic blood pressure above the median had lower IMT values than carriers with a systolic blood pressure equal or below the median. All these effects were more pronounced in females and remained significant after adjustment for sex, age, BMI, systolic blood pressure and serum apolipoprotein B levels. No significant differences between the carriers and the noncarriers could be found for BMI, insulin sensitivity or frequency of type II diabetes. CONCLUSIONS: The results of our study demonstrate that the presence of the Arg972 allele is associated with lower IMT values of the carotid arteries. This finding is partly explained by lower serum levels of apolipoprotein B in carriers. The protective effect of the Gly972 Arg mutation seems to be stronger in the presence of a higher systolic blood pressure. Our data contradict previous findings suggesting an increased risk for insulin resistance, type II diabetes and atherosclerotic vascular disease in carriers of the mutation.

Adult↗
PubMed2003

Delayed aortic rupture after radiochemotherapy and esophagectomy for esophageal cancer.

Spontaneous rupture of major vessels is a known though rare complication in treatment of patients with esophageal cancer, but its pathophysiology is not very well understood. We herein report about the sudden death of a 42-year-old man due to spontaneous aortic rupture, 11 days after transthoracic esophagectomy. Because of a locally advanced squamous cell carcinoma of the distal esophagus, which was considered irresectable at the time of presentation, the patient had received one course of chemotherapy followed by synchronous chemoradiation (60 Gy, 5-fluorouracil and cisplatin) prior to surgery. We discuss the patho-anatomic findings of the postmortem examination concerning alterations of the aortic wall and the potential correlations with aggressive radiochemotherapy protocols.

Adult↗
PubMed2002

[Sinugenic metastasis of bilateral renal cell carcinoma (hypernephroma)].

The paranasal sinuses are a rare location of metastases. The most frequent infraclavicular primary tumor is the renal cell carcinoma (hypernephroma). We report a case of a 64-old-woman with a bilateral renal cell carcinoma and metastases in the paranasal sinuses with destruction of the skull base. If symptoms such as progressive indolent periorbital swelling or intermittent epistaxis occur in adults, one should consider a metastasis of a renal cell carcinoma to the paranasal sinuses even 10 years after nephrectomy.

Biopsy↗
PubMed2001

An isoform of the coactivator AIB1 that increases hormone and growth factor sensitivity is overexpressed in breast cancer.

The AIB1 (amplified in breast cancer 1) protein is a coactivator that potentiates the transcriptional activity of nuclear hormone receptors, and its gene is amplified in a subset of human breast cancers. Here we report a splice variant of AIB1 mRNA that lacks the exon 3 sequence. We determined that the AIB-Delta3 mRNA encoded a 130-kDa protein that lacks the NH(2)-terminal basic helix-loop-helix and a portion of the PAS (Per-Arnt-Sim homology) dimerization domain. The 130-kDa protein was detected in MCF-7 breast cancer cells at levels that were 5-10% of the full-length protein, whereas in non-transformed mammary epithelium lines, the AIB-Delta3 protein was present at significantly lower levels compared with the full-length AIB1. Consistent with this finding, the abundance of AIB1-Delta3 mRNA was increased in human breast cancer specimens relative to that in normal breast tissue. To determine whether there were phenotypic changes associated with the overexpression of the AIB-Delta3 isoform, we performed functional reporter gene assays. These revealed that the ability of AIB1-Delta3 to promote transcription mediated by the estrogen or progesterone receptors was significantly greater than that of the full-length protein. Surprisingly, the AIB1-Delta3 isoform was also more effective than AIB1 in promoting transcription induced by epidermal growth factor. Overexpression of AIB1-Delta3 may thus play an important role in sensitizing breast tumor cells to hormone or growth factor stimulation.

Acetyltransferases↗
PubMed2001

Negative cooperativity and aggregation in biphasic binding of mastoparan X peptide to membranes with acidic lipids.

The change of Trp fluorescence intensity when large vesicles with 10% acidic lipid are added to mastoparan X solutions reflects a fast and a slow binding process. By means of a novel procedure of data analysis that takes advantage of so-called mass conservation plots we have separated association isotherms related to: (i) the apparent fast pre-equilibrium; and (ii) the final equilibrium, respectively. This approach also reveals that the intrinsic fluorescence signal of the slow binding is considerably raised against that of the fast binding, presumably indicating a penetration of bound peptide from the lipid/water interface into the apolar lipid core. The shape of either binding curve discloses a pronounced tendency of aggregation. Furthermore, it turns out that in the slow process the final binding ratio decreases markedly compared with the initial fast binding ratio. Accordingly the occupation of final binding sites must exert a substantial effect of negative cooperativity on the affinity of the interfacial binding states.

Acids↗
PubMed2001

Ribozyme targeting demonstrates that the nuclear receptor coactivator AIB1 is a rate-limiting factor for estrogen-dependent growth of human MCF-7 breast cancer cells.

Human breast tumorigenesis is promoted by the estrogen receptor pathway, and nuclear receptor coactivators are thought to participate in this process. Here we studied whether one of these coactivators, AIB1 (amplified in breast cancer 1), was rate-limiting for hormone-dependent growth of human MCF-7 breast cancer cells. We developed MCF-7 breast cancer cell lines in which the expression of AIB1 can be modulated by regulatable ribozymes directed against AIB1 mRNA. We found that depletion of endogenous AIB1 levels reduced steroid hormone signaling via the estrogen receptor alpha or progesterone receptor beta on transiently transfected reporter templates. Down-regulation of AIB1 levels in MCF-7 cells did not affect estrogen-stimulated cell cycle progression but reduced estrogen-mediated inhibition of apoptosis and cell growth. Finally, upon reduction of endogenous AIB1 expression, estrogen-dependent colony formation in soft agar and tumor growth of MCF-7 cells in nude mice was decreased. From these findings we conclude that, despite the presence of different estrogen receptor coactivators in breast cancer cells, AIB1 exerts a rate-limiting role for hormone-dependent human breast tumor growth.

Animals↗
PubMed2001

Expression of the nuclear coactivator AIB1 in normal and malignant breast tissue.

The gene of the nuclear receptor coactivator AIB1 (amplified in breast cancer 1) is amplified in breast cancer cell lines as well as in breast tumor tissues. AIB1 mRNA is often highly expressed (>60%) in primary breast tumors and it has been shown that AIB1 enhances estrogen and progesterone dependent transcription in vitro. Therefore, it has been postulated that AIB1 contributes to the development of breast cancer. However, to date, it has not been shown that AIB1 amplification and overexpression correlates with elevated protein levels in breast cancer tissues. In this study we analyzed protein levels of AIB1 in normal and breast tumor tissues by immunohistochemistry. We compared 41 human breast tumor tissues with 24 normal breast tissue samples and found that AIB1 stained in the nuclei of approximately 46% of the tumors and 30% of the normal tissues. Overall, AIB1 protein levels were significantly higher in tumor tissue than in normal tissue and the highest levels of nuclear staining were found exclusively in breast tumor tissues in 9.8% of the cases. These data suggest that increased AIB1 mRNA expression does not always translate into elevated protein levels and that AIB1 most likely will be relevant to the etiology of a subset of about 10% of breast carcinomas.

Adult↗
PubMed2001

Do human platelets express COX-2?

The rate-limiting enzyme in prostaglandin (PG)- and thromboxane (TX)-synthesis is known as cyclooxygenase (COX). The COX-enzyme family consists of the classical COX-1 and the inducible COX-2-enzyme. To investigate whether platelets contain COX-2, we measured thiobarbituric acid reactive substances (TBARS) after either blocking COX-1 or COX-2 or adding compounds known to affect COX-expression. To stimulate platelets' different reagents such as collagen, thrombin and arachidonic acid (AA) were used. The inhibitors used in this study were acetylsalicylic acid (ASA), indomethacin and NS-398. Using the western-blot technique, we failed to detect COX-2 in platelets while COX-1 was detectable. We were not able to discover COX-2 in platelets using the methods we applied. As the amount of COX-2 in platelets might be below the detection limit of the methods used, the biological relevance COX-2 in platelets, if even existing at low amounts, remains to be established.

Adult↗
PubMed2000

Deletion in the promoter region and altered expression of Pitx3 homeobox gene in aphakia mice.

Mouse aphakia (ak) is a recessive phenotype that spontaneously occurs in the 129/Sv-SlJ strain and is characterized by small eyes that lack a lens. We have recently identified a homeobox-containing gene, Pitx3, and have shown that it is expressed in the developing lens and maps to chromosome 19 close to ak in mouse. Human PITX3 gene was found to underlie anterior segment dysgenesis and cataracts. We have now obtained the entire sequence of the mouse Pitx3 gene including 10 kb of the 5' region and 5 kb of the 3' region. Of several microsatellite repeat regions identified within the Pitx3 sequence, one was informative for linkage analysis. No recombination was observed between ak and the Pitx3 marker, indicating that these two loci are closely linked (0.2 +/- 0.2 cM). Additionally, Pitx3 transcripts were not detected in the ak/ak mice either in the lens placode or at later developmental stages of the lens by in situ hybridization. Since no differences were previously found between ak/ak and wild-type sequences in the Pitx3 coding region, we hypothesized that an etiologic mutation is located in the promoter or other regulatory regions. To test this hypothesis we studied the 5' flanking region of the Pitx3 gene. This analysis revealed a deletion of 652 bp located 2.5 kb upstream from the start point of the Pitx3 5' UTR sequence in ak/ak mice. The deletion co-segregated with the ak mutation and was not detected in 16 samples from 10 different mouse strains including the founder strains. Analysis of the 652 bp region identified sequences similar to consensus binding sites for transcription factors AP-2 and Maf that were shown to play a critical role in lens determination. These lines of evidence suggest that the abnormal ocular development in the aphakia mouse is due to the deletion upstream of the Pitx3 gene.

Acetyltransferases↗
PubMed1999

Aminoguanidine inhibits albuminuria, but not the formation of advanced glycation end-products in skin collagen of diabetic rats.

Aminoguanidine, an inhibitor of advanced glycation reactions in vitro, inhibits the development of diabetic complications in animal models of diabetes, suggesting that it acts by inhibition of advanced glycation reactions in vivo. However, effects of aminoguanidine on the formation of specific advanced glycation end-products (AGEs) in vivo have not been rigorously examined. Therefore, we studied the effects of aminoguanidine on the formation of pentosidine and N(epsilon)-(carboxymethyl)lysine (CML), measured by analytical chemical methods, in collagen of streptozotocin-diabetic Lewis rats at doses which ameliorated urinary albumin excretion, an index of diabetic nephropathy. At 12 weeks, diabetic animals had fivefold higher blood glucose, threefold higher glycated hemoglobin and fivefold higher collagen glycation, compared to metabolically healthy controls; pentosidine and CML in skin collagen were increased by approximately 30 and 150%, respectively. Administration of aminoguanidine, 50 mg/kg by daily intraperitoneal injection, significantly inhibited the development of albuminuria (approximately 60%, P < 0.01) in diabetic rats, without an effect on blood glucose or glycation of hemoglobin or collagen. Surprisingly, aminoguanidine failed to inhibit the increase in pentosidine and CML in diabetic rat skin collagen. Similar results were obtained in an independent experiment in which aminoguanidine was administered in drinking water at a dose of 0.5 g/l. We conclude that the therapeutic benefits of aminoguanidine on albuminuria may not be the result of inhibition of AGE formation.

Albuminuria↗
PubMed1999

Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma.

PURPOSE: Families with von Hippel-Lindau disease have variable risk of pheochromocytoma. Patients with von Hippel-Lindau disease and pheochromocytoma identified by screening can have no characteristic signs or symptoms. Families with von Hippel-Lindau disease were screened and followed to describe the natural history of von Hippel-Lindau pheochromocytoma, and to correlate these findings with von Hippel-Lindau germline mutation. MATERIALS AND METHODS: Between 1988 and 1997, 246 individuals with von Hippel-Lindau disease were identified (von Hippel-Lindau group). Between August 1990 and June 1997, 26 consecutive patients with sporadic pheochromocytoma were evaluated (sporadic group). RESULTS: A total of 64 patients with von Hippel-Lindau disease had manifestations of pheochromocytoma, including 33 newly diagnosed during screening at the National Institutes of Health and 31 previously treated (93 adrenal and 13 extra-adrenal pheochromocytomas). Germline von Hippel-Lindau gene missense mutation was associated with extra-adrenal pheochromocytoma, younger age at presentation and the only patient with metastases. Of the 33 newly diagnosed patients with von Hippel-Lindau disease 4 had pheochromocytoma 2 times (37 pheochromocytomas) during followup. Of these pheochromocytomas 35% (13 of 37) were associated with no symptoms, normal blood pressure and normal catecholamine testing. Comparison of urinary catecholamines in the von Hippel-Lindau and sporadic groups demonstrated increased epinephrine, metanephrines and vanillylmandelic acid in the sporadic group. Analysis of urinary catecholamine excretion in the von Hippel-Lindau and sporadic groups together demonstrated a correlation between tumor size, and urinary metanephrines, vanillylmandelic acid, norepinephrine, epinephrine and dopamine. In 12 patients without signs or symptoms of pheochromocytoma 17 newly diagnosed pheochromocytomas were followed for a median of 34.5 months without morbidity. Median tumor doubling time was 17 months. CONCLUSIONS: Von Hippel-Lindau gene missense mutation correlated with the risk of pheochromocytoma in patients with von Hippel-Lindau disease. These findings support a von Hippel-Lindau disease clinical classification, wherein some families are at high risk for manifestations of pheochromocytoma. Von Hippel-Lindau disease pheochromocytomas identified by screening were smaller and less functional than sporadic pheochromocytomas.

Adrenal Gland Neoplasms↗
PubMed1998

Nerve growth factor evokes hyperalgesia in mice lacking the low-affinity neurotrophin receptor p75.

Endogenous nerve growth factor (NGF) has been shown to be an important mediator of inflammatory pain and exogenous application of recombinant human NGF (rhNGF) produces pain and hyperalgesia in animals and humans. Since NGF can act through two receptors types, the high affinity tyrosine kinase A (trkA) receptor and the low affinity p75 receptor, we used transgenic mice lacking p75 to analyse the relative importance of these receptors. After systemic injection of rhNGF (5 mg/ kg), pharmacokinetic studies revealed similar serum levels and elimination profiles of exogenously administered rhNGF in both strains of mice. Although animals lacking p75 have increased mechanical and thermal withdrawal thresholds they developed both heat and mechanical hyperalgesia after systemic injection of rhNGF whose magnitude did not differ significantly from wildtype animals. This means that NGF-induced hyperalgesia can occur in the absence of the p75 receptor and suggests that the trkA receptor is sufficient to mediate the acute noxious action of NGF.

Animals↗
PubMed1998

Nerve growth factor (NGF) and diabetic neuropathy in the rat: morphological investigations of the sural nerve, dorsal root ganglion, and spinal cord.

A number of functions for nerve growth factor (NGF) have been described over the past years, including its role for neuronal function and regeneration during toxic or metabolic neuropathies. In order to further assess the effects of NGF on the somatosensory system in diabetic neuropathy, the sural nerve, dorsal root ganglia (DRG), and dorsal horn of the spinal cord were investigated by morphological and quantitative methods in rats after 12 weeks of uncontrolled streptozotocin-induced diabetes mellitus. The results from our study suggest a twofold effect of NGF: (1) In sural nerve treatment with NGF (0.1 or 0.5 mg/kg) for 12 weeks was able to reverse distinct diabetes-related alterations in myelinated nerve fiber morphology, such as myelin thickness. These changes occurred in the entire myelinated population of sensory nerves and were not restricted to nociceptive nerve fibers. (2) The NGF effect on neurotransmitters of the sensory, nociceptive system was reflected by increased CGRP and substance P content in the DRG and in the dorsal horn of the spinal cord. No change of trkA receptor immunostaining was seen in DRGs of diabetic rats; however, a reduction of trkA immunoreactivity of DRG neurons was noted after long-term NGF treatment of healthy controls. The data demonstrate that NGF regulates a number of neuronal parameters along peripheral and central parts of the somatosensory pathway in the adult. This neurotrophic support may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy.

Animals↗