Giant cystic lymphangioma of the stomach.
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Adolescent↗
Biomedical subjects
H Müller
Publications and source records attributed to H Müller.
Experimental infection of mice with Borna disease virus (BDV): replication and distribution of the virus after intracerebral infection.
To develop an animal model resembling natural asymptomatic Borna disease virus (BDV) infections, BDV He/80 rat brain homogenate was passaged four times in adult SJL/J mice. Within 12 months of observation, mice did not develop overt signs of disease. Nucleotide sequencing of the rat isolate and the mouse isolates at the fourth passage revealed no difference in the deduced amino acids. Viral RNA was found in brain, heart, kidney, lung, liver, and urinary bladder. Infectious virus was isolated from brain, but also from heart and lung tissue. Immunohistochemically, BDV was demonstrated in nerves in the abdominal cavity, ganglion coeliacum, and adrenal glands, but not in organ parenchyma. Occasionally, viral RNA was detected in mononuclear blood cells.
Animals↗
Loss of N-linked glycans in the V3-loop region of gp120 is correlated to an enhanced infectivity of HIV-1.
We describe mutants of human immunodeficiency virus type-1 (HIV-1) strain NL4-3, which are lacking the thirteenth, fifteenth, or seventeenth sites for N-linked glycosylation (g13, g15, g17) of the envelope protein gp120. All three sites are located within the hypervariable V3 loop region of gp120. Those mutants lacking carbohydrates g15 or combinations of g15/g17 showed markedly higher infectivity for GHOST cells (human osteosarcoma cells) expressing CXCR4 (GHOST-X4), compared to the fully glycosylated NL4-3 wild type virus. In addition, these mutants could also infect cells which exhibits low background expression of CXCR4, corresponding to <10% of that observed for GHOST-X4 cells. In addition to the enhanced infectivity observed, mutants lacking g15 and g17 showed increased resistance to inhibition by SDF-1, the natural ligand of CXCR4. Thus, loss of the oligosaccharides g15 and g17 in the V3 region of gp120 markedly influences CXCR4-specific infection.
Amino Acid Sequence↗
Effects of early postfiltration ocular hypotony on visual acuity, long-term intraocular pressure control, and posterior segment morphology.
PURPOSE: To determine whether hypotony after filtration surgery has any influence on visual acuity and intraocular pressure (IOP) lowering. PATIENTS AND METHODS: We prospectively investigated 43 eyes of 43 patients undergoing trabeculectomy without the use of antimetabolites for 12 months. RESULTS: The lowest postoperative IOP valued 4.9 +/- 3.6 mm Hg (range, 0-14 mm Hg). It correlated statistically significant with the IOP 6 weeks (P = 0.016), 6 months (P = 0.009), and 1 year after surgery (P = 0.027). Eyes with a deterioration of visual acuity 6 weeks after surgery had undergone a stronger postoperative hypotony (correlation with lowest postoperative IOP, P = 0.035). The mean period with an IOP less than 5 mm Hg was 3.5 +/- 8.0 days, and the mean period with an IOP less than 10 mm Hg lasted 45.4 +/- 68.8 days (range, 0-276 days). A hypotony score based on IOP and duration of hypotony was introduced. A correlation was detected between morphologic signs of hypotony, such as tiny retinal folds, at the 6-month follow-up and the duration of hypotony (P = 0.029) and hypotony score (P = 0.001). CONCLUSIONS: Hypotony after filtration surgery may decrease visual acuity in the early postoperative period. Conversely, early postoperative hypotony correlated with better long term IOP control. There was no deleterious effect on visual acuity after 6 months.
Adult↗
Protein import channel of the outer mitochondrial membrane: a highly stable Tom40-Tom22 core structure differentially interacts with preproteins, small tom proteins, and import receptors.
The preprotein translocase of the yeast mitochondrial outer membrane (TOM) consists of the initial import receptors Tom70 and Tom20 and a approximately 400-kDa (400 K) general import pore (GIP) complex that includes the central receptor Tom22, the channel Tom40, and the three small Tom proteins Tom7, Tom6, and Tom5. We report that the GIP complex is a highly stable complex with an unusual resistance to urea and alkaline pH. Under mild conditions for mitochondrial lysis, the receptor Tom20, but not Tom70, is quantitatively associated with the GIP complex, forming a 500K to 600K TOM complex. A preprotein, stably arrested in the GIP complex, is released by urea but not high salt, indicating that ionic interactions are not essential for keeping the preprotein in the GIP complex. Under more stringent detergent conditions, however, Tom20 and all three small Tom proteins are released, while the preprotein remains in the GIP complex. Moreover, purified outer membrane vesicles devoid of translocase components of the intermembrane space and inner membrane efficiently accumulate the preprotein in the GIP complex. Together, Tom40 and Tom22 thus represent the functional core unit that stably holds accumulated preproteins. The GIP complex isolated from outer membranes exhibits characteristic TOM channel activity with two coupled conductance states, each corresponding to the activity of purified Tom40, suggesting that the complex contains two simultaneously active and coupled channel pores.
Fungal Proteins↗
Cell cycle dependent DNA break increase in ataxia telangiectasia lymphoblasts after radiation exposure.
The most striking feature of ataxia telangiectasia (AT) cells is their profound sensitivity to ionising radiation. A deficiency in the rejoining of radiation induced DNA breaks has been suggested to be responsible for AT radiosensitivity; however, the existing literature is controversial. A subpopulation, which is present in irradiated AT lymphoblasts, but rarely in controls, has been reported previously. The cells that make up this subpopulation harbour highly fragmented DNA and are responsible for the overall increase in DNA breaks soon after irradiation in AT lymphoblasts. This study examines the influence of the cell cycle on the highly damaged subpopulation. The frequency of highly damaged cells was highest when AT lymphoblasts were irradiated during the G2/M phase. In contrast, AT lymphoblasts irradiated during the G0/G1 phase displayed a frequency similar to control cells. Thus, only G2/M and to some extent S phase cells contribute to an increased DNA break number in AT lymphoblasts early after irradiation. These findings might explain several inconsistencies reported in the literature.
Adult↗
Healing of active, non-atrophic autoimmune gastritis by H. pylori eradication.
BACKGROUND AND AIMS: The antigastric antibodies present in Helicobacter pylori infection act as a marker for an ongoing antigastric autoimmune process in the gastric mucosa, which can already be diagnosed in the non-atrophic stage. In a retrospective, uncontrolled study, therefore, we investigated the question as to whether this type of gastritis can be healed by the eradication of H. pylori. PATIENTS AND METHODS: In 80 patients with an active, not yet atrophic autoimmune gastritis, we analysed a maximum of four investigations per patient over a period of up to 39.5 months. The following parameters were graded in the antral and corpus mucosa prior to and after H. pylori eradication treatment: grade and activity of the gastritis, H. pylori colonization, atrophy, parietal cell hypertrophy, and incidence of intestinal metaplasia. In addition, the typical parameters for this type of gastritis, such as grade of the periglandular lymphocytic infiltration, grade of glandular destruction and incidence of nodular ECL cell proliferates in the corpus mucosa were determined. RESULTS: In 64 patients (80%), H. pylori eradication treatment was followed by healing of the active autoimmune corpus gastritis, that is, the activity of the gastritis disappeared, and lymphocytic infiltration of the glands, glandular destruction and parietal cell hypertrophy was found to be significantly reduced. CONCLUSIONS: Our uncontrolled, retrospective study confirms the existence of an active, not yet atrophic autoimmune gastritis as a sequela of H. pylori infection.
Adult↗
Healing of lymphocytic gastritis by eradication of Helicobacter pylori.
BACKGROUND: It is not yet clear whether lymphocytic gastritis might not be a sequela of Helicobacter pylori (Hp) infection. The aim of the present pilot study was, therefore, to investigate whether lymphocytic gastritis can be cured by Hp eradication, which, if affirmed, would provide indirect evidence for an etiopathogenic relationship. PATIENTS AND METHODS: 98 of 220 patients with lymphocytic gastritis diagnosed between 1988 and 1998 were investigated at least twice, with 61 of them undergoing Hp eradication treatment. In 29 of these patients, the pretreatment histological work-up using the Warthin-Starry silver stain revealed Hp colonisation, while in the remaining 32 patients the biopsies from the antrum and corpus were negative for Hp. The other 37 patients received no treatment, and served as a control group. RESULTS: Both in the group with Hp-positive, and in the group with Hp-negative histology prior to treatment, eradication treatment led to healing of the gastritis, i.e. to regression of the gastritis parameters including normalisation of the intra-epithelial lymphocyte count, in 93.1% and 84.3% of the cases, respectively. In the control group the histological findings did not change. CONCLUSIONS: The results of our retrospective study support the notion that most cases of lymphocytic gastritis might be a consequence of Hp infection. This, however, needs to be clarified definitively by a prospective, randomized, double-blind study.
Aged↗
Effectiveness of Trastuzumab (Herceptin) in a patient with locally recurrent breast cancer after cardiac failure caused by severe cytotoxic pretreatment.
In HER2-positive breast cancer patients, the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) may improve overall survival. No reports exist regarding the application of trastuzumab in patients with cytotoxically induced cardiac failure and decreased left ventricular ejection fraction or about locally recurrent and advanced disease. In this case report, trastuzumab resulted in a complete and long-lasting response of recurrent and locally advanced breast cancer and was well tolerated in a severely cytotoxically pretreated patient with cardiac failure. We encourage other oncologists to offer trastuzumab also to severely cytotoxically pretreated patients with conditions after cardiac insufficiency or with locally advanced breast cancer.
Antibodies, Monoclonal↗
[Persistence of FDMV and its effects on disease control strategies].
It is well-known that foot-and-mouth disease virus (FMDV) causes a persistent infection, lasting for more than 28 days, in cattle, sheep, goat as well as some other ruminant species, but not in pigs. Although convincing evidence for virus transmission is missing, these carrier animals have to be considered as a potential risk of infection. Some aspects of FMDV persistence are presented and discussed with regard to disease control strategies.
Animals↗
A polymorphism in the ATM gene modulates the penetrance of hereditary non-polyposis colorectal cancer.
Germ-line mutations in MLH1 and MSH2 genes predispose to hereditary non-polyposis colorectal cancer (HNPCC) syndrome, but they do not predict a specific phenotype of the disease. We speculated that the ataxia-telangiectasia mutated gene (ATM) was a candidate gene to modulate the phenotypic expression of HNPCC, as heterozygous individuals for germ-line ATM mutations have been considered at higher risk of developing epithelial malignancies. The frequency of the ATM D1853N polymorphism was evaluated in 167 individuals from 20 HNPCC families in which MLH1 or MSH2 germ-line mutations co-segregated with the disease. Among the 67 MLH1 or MSH2 mutation carriers, the ATM 1853N variant was associated with a significantly higher incidence of colorectal and other HNPCC-related cancers, when compared with individuals carrying the ATM 1853D variant [12/13 (92%) vs. 31/54 (57.5%); p = 0.02]. MLH1 and MSH2 mutation carriers who concomitantly carried the ATM 1853N variant, had an 8 times increased risk of developing colorectal and other HNPCC-related cancers (OR: 8.9; p = 0.02), when compared with MLH1 or MSH2 mutation carriers with the ATM 1853D variant. Our results suggest that the ATM D1853N polymorphism modulates the penetrance of MLH1 and MSH2 germ-line mutations.
Adaptor Proteins, Signal Transducing↗
Effects of adjuvant tamoxifen on the endometrium in postmenopausal women with breast cancer: a prospective long-term study using transvaginal ultrasound.
PURPOSE: To study the value of transvaginal ultrasound (TVS) in endometrial screening of postmenopausal breast cancer patients treated with tamoxifen. PATIENTS AND METHODS: In 247 tamoxifen-treated (20 to 30 mg/d for >/= 2 years) women and 98 controls, the endometrium was prospectively followed-up by means of TVS every 6 months for up to 5 years. Patients with homogeneous endometrium of more than 10-mm thickness were then scanned repeatedly every 3 months. RESULTS: The mean endometrial thickness was 3.5 +/- 1.1 mm before treatment and increased to a maximum of 9. 2 +/- 5.1 mm after 3 years of tamoxifen application (P: <.0001), which was significantly (P: <.0001) thicker compared with controls. Fifty-two asymptomatic patients with thickened or morphologically suspect endometrium underwent hysteroscopy and dilatation and curettage (D&C), resulting in four uterine perforations. Histopathologically, atrophy was found in 38 patients (73.1%), polyps in nine, hyperplasia in four, and endometrial cancer in one case. In 20 screened patients who reported vaginal bleeding, five atrophies (25%), five polyps, four hyperplasias, and two endometrial cancers were found. Before hysteroscopy and D&C were performed, 36 (69.2%) of 52 asymptomatic and four (20%) of 20 symptomatic patients were scanned by repeated TVS over 2 to 30 months. Invasive diagnostic procedures were significantly (P: <.05) more frequent in younger and obese patients. In the controls, one asymptomatic polyp and one symptomatic hyperplasia were found. CONCLUSION: In tamoxifen-treated patients, TVS offered a high false-positive rate, even with a cutoff value of 10 mm for endometrial thickness and repeated TVS scans. Increased iatrogenic morbidity and only one asymptomatic endometrial carcinoma do not warrant endometrial screening by TVS in tamoxifen-treated patients.
Adult↗
Experimental and natural borna disease virus infections: presence of viral RNA in cells of the peripheral blood.
Cells of the peripheral blood of experimentally and naturally borna disease virus (BDV)-infected animals and of human psychiatric patients and healthy individuals were analyzed for the presence of viral RNA using a BDV-p40-specific nested reverse transcription-polymerase chain reaction (RT-PCR). The assay proved to be highly sensitive as 10 RNA molecules were reproducibly amplified. BDV RNA was detected in blood cells of experimentally infected immunocompetent mice and rats. Mice were persistently infected without showing clinical signs of borna disease (BD), whereas the rats suffered from acute BD. Among 19 horses examined, five were positive for viral RNA in the blood. In a flock of sheep with a history of BD, 1 out of 25 clinically healthy animals was positive. BDV RNA was also detected in cells of the peripheral blood of 10 out of 27 selected humans with psychiatric disorders, and in 2 out of 13 healthy individuals. Remarkably, BDV-specific RNA was present in some cases in the absence of BDV-specific antibodies. Sequence analysis of PCR products confirmed the specificity of the amplification system. The presence of BDV RNA in the blood of naturally and experimentally BDV-infected individuals may point to an incidental but relevant role of blood for the spread of BDV in the infected organism, as well as for the transmission of BDV to other individuals.
Animals↗
Germline alterations in the cyclooxygenase-2 gene are not associated with the development of extracolonic manifestations in a large swiss familial adenomatous polyposis kindred.
Familial adenomatous polyposis (FAP) is an autosomal dominant condition leading to the development of multiple colorectal polyps and other features. Intrafamilial variation in phenotype is known to occur in FAP; despite carrying the same causing mutation in the APC gene, disease expression may considerably differ in affected individuals, likely due to the existence of modifier genes. Several lines of evidence suggest the cyclooxygenase-2 (COX-2) gene to be a candidate modifier in FAP. Since COX-2 appears to be expressed in tissues prone to be affected in FAP, it might influence the occurrence of extracolonic manifestations in this disorder. Herein, we investigated whether alterations in the COX-2 gene are involved in the development of extracolonic polyps and extragastrointestinal features. Mutational analysis using single-strand conformation polymorphism (SSCP) in 130 members of a FAP family displaying strong phenotype variation revealed 3 polymorphic sites within the coding region of the COX-2 gene. None of these allelic variants, however, segregated with a particular disease phenotype. In addition, expression analysis was performed in 31 family members with representative phenotypes. Neither of the two polymorphisms detected within the COX-2 promoter was associated with a given phenotype nor was there a significant difference in quality or quantity of COX-2 mRNA in lymphocytes as measured by reverse transcription- and real time quantitative reverse transcription PCR (RT-PCR and TaqMan). In conclusion, germline alterations in the COX-2 gene are unlikely to account for the development of extracolonic disease in FAP patients.
Adenomatous Polyposis Coli↗
Microsatellite instability in colorectal cancer.
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Colorectal Neoplasms↗
[Hereditary cancer syndromes in gynecology: what the practitioner needs to know!].
During the last 5 years progress in molecular genetics has offered the possibility of genetic testing for inherited mutations of cancer-predisposing genes. The exact cellular function and carcinogenic potential of these genes is yet not completely understood. Only in 5-20% of all cancers inherited genetic mutations play an important role in the polygenic and multifactorial nature of the disease. Identification of inherited cancer syndromes, predictive genetic testing, and counselling of women and family members at increased risk is of clinical importance. The debate surrounding presymptomatic diagnostic testing and adequate programmes for early cancer detection, prevention or clinical follow-up continues.
Breast Neoplasms↗
The E2F transcription factors: key regulators of cell proliferation.
Ever since its discovery, the RB-1 gene and the corresponding protein, pRB, have been a focal point of cancer research. The isolation of E2F transcription factors provided the key to our current understanding of RB-1 function in the regulation of the cell cycle and in tumor suppression. It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked. Certain aspects of RB-1 function, for instance its role in differentiation, cannot be easily explained by the current models of pRB-E2F interaction. One reason is that pRB has targets different from E2F, molecules like MyoD for instance. Another reason may be that we have not completely understood the full complexity of E2F function, itself. In this review, we will try to illuminate the role of E2F in pRB- and p53-mediated tumor suppression pathways with particular emphasis on the aspect of E2F-mediated transcriptional regulation. We conclude that E2F can mediate transcriptional activation as well as transcriptional repression of E2F target genes. The net effect of E2F on the transcriptional activity of a particular gene may be the result of as yet poorly understood protein-protein interactions of E2F with other components of the transcriptional machinery, as well as it may reflect the readout of the different ways of regulating E2F activity, itself. We will discuss the relevance of a thorough understanding of E2F function for cancer therapy.
Animals↗
Natural products in drug discovery.
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Biological Products↗