["Giant" fibrovascular esophageal polyp]. / "Gigantischer" fibrovaskulärer Polyp des Ösophagus.

Fibrovascular polyps are rare mesenchymal tumors that arise mainly in the cricopharyngeal portion of the esophagus. They may protrude distally to become "giant" pedunculated lesions filling almost the entire esophageal lumen. Histologically they contain varying amounts of adipose, fibrous and vascular tissues and belong to spindle cell lipomas according to the classification of soft tissue tumors. Immediate resection of these benign lesions is warranted as they may be regurgitated and cause asphyxia. These lesions are usually treated by open surgery (left cervicotomy) or, less invasively, by peroral endoscopic surgery. Polyp removal by flexible endoscopy has been described but may be hazardous if its stalk is broad-based. In this report the case of a 73-year-old male with dysphagia is described in whom a "giant" fibrovascular polyp was diagnosed endoscopically and promptly removed surgically by the peroral route. At control endoscopy 14 months later, the asymptomatic patient was free of polyp recurrence.

Extant forest plantations as a potential bridge between social needs and ecological management: a comparative case study analysis.

In the face of global deforestation, there is a challenge to balance the management of areas of high conservation concern and social interests. As a response to the growing human-environment interface and the use of forests for subsistence, plantations became a management tool to provide for wood harvesting during the 1970s. Some plantations were subsequently protected from harvest as conservation of all forests increased. Plantations that are now illegal to harvest can cause local animosities toward forest protection to increase and may also result in concentrated harvesting impacts on surrounding natural forests. In this article, we analyzed case studies of plantations from El Salvador and Niger. By utilizing distinctly disparate case studies, commonalities between the two can illuminate possible management lessons. In the comparison of El Salvador and Niger forest plantations we found the following commonalities: utilizing plantations for sustainable harvest has the to potential to reduce animosity between managers and stakeholders; plantations can serve as a risk-averse testing ground for novel managerial practices; and the sustainable harvest of plantations can reduce deforestation and impacts on biodiversity in natural remnant forests. We argue that extant plantations currently under illegal harvesting legislation could become the epicenters of social and ecological conservation through a management shift to sustainable harvesting. By focusing on these relics, managers could work with stakeholders to change unduly burdening restrictions and promote cooperation between conservationists and local populations.

[Segmental necrotizing colitis in a patient with E. coli O104:H4 infection]. / Segmentale nekrotisierende Kolitis bei einem Patienten mit EHEC-Infektion vom Typ O104:H4.

A 29-year-old man presented with abdominal cramps and bloody diarrhoea. Blood tests revealed elevated C-reactive protein (21.3 mg/dL; normal range 0.01 - 0. 82 mg/dL) and white blood cells (28200/µL, normal range 4000 - 10000/µL). Stool tests were negative for enteropathogenic bacteria and Clostridium difficile toxins A/B. Ultrasound and computed tomography showed massive swelling of the transverse colon and right colonic flexure. At endoscopy, circular necrosis of the mucosa was encountered in the proximal segments of the colon whereas distal parts of the organ showed patchy inflammation of minor severity. Extended stool testing identified Escherichia coli type O104:H4 as the causative microorganism. There was no evidence for haemolytic uraemic syndrome. Under conservative treatment the patient recovered clinically, serologically and endoscopically. At follow-up endoscopy, longitudinal ulcers and vital mucosa were present. In this case report the segmental pattern of mucosal necrosis in a patient with EHEC infection is noteworthy.

Repair of hydantoins, one electron oxidation product of 8-oxoguanine, by DNA glycosylases of Escherichia coli.

8-oxoguanine (8-oxoG), induced by reactive oxygen species and arguably one of the most important mutagenic DNA lesions, is prone to further oxidation. Its one-electron oxidation products include potentially mutagenic guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) because of their mispairing with A or G. All three oxidized base-specific DNA glycosylases of Escherichia coli, namely endonuclease III (Nth), 8-oxoG-DNA glycosylase (MutM) and endonuclease VIII (Nei), excise Gh and Sp, when paired with C or G in DNA, although Nth is less active than the other two. MutM prefers Sp and Gh paired with C (kcat/K(m) of 0.24-0.26 min(-1) x nM(-1)), while Nei prefers G over C as the complementary base (k(cat)/K(m) - 0.15-0.17 min(-1) x nM(-1)). However, only Nei efficiently excises these paired with A. MutY, a 8-oxoG.A(G)-specific A(G)-DNA glycosylase, is inactive with Gh(Sp).A/G-containing duplex oligonucleotide, in spite of specific affinity. It inhibits excision of lesions by MutM from the Gh.G or Sp.G pair, but not from Gh.C and Sp.C pairs. In contrast, MutY does not significantly inhibit Nei for any Gh(Sp) base pair. These results suggest a protective function for MutY in preventing mutation as a result of A (G) incorporation opposite Gh(Sp) during DNA replication.

Lovastatin blocks basic fibroblast growth factor-induced mitogen-activated protein kinase signaling in coronary smooth muscle cells via phosphatase inhibition.

We have recently reported that the activation of mitogen-activated protein kinase (MAPK) through specific protein kinase C (PKC) isoforms is required for basic fibroblast growth factor (bFGF)-induced proliferation of coronary smooth muscle cells (cSMC). In this study, we investigated the effects of the 3hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin on bFGF-induced signal transduction in cSMC. The present study shows that lovastatin inhibits bFGF-stimulated DNA synthesis in cSMC, and that this inhibition is reversed by mevalonate (50 micromol/l) and by geranylgeranyl-pyrophosphate (1-5 micromol/l). Although lovastatin prevented Ras farnesylation the amount of bFGF-stimulated MAPK phosphorylation decreased only partially after lovastatin treatment. In addition, lovastatin pretreatment resulted in a sustained phosphorylation of MAPK. We observed a dose-dependent lovastatin-dependent increase in PKC activity, which could be prevented by mevalonate. This increase was comparable to the one induced by calyculin A (2 nmol/l), an inhibitor of protein phosphatase PP-1 and PP-2A. Lovastatin inhibited the expression of the PP-1 protein, which is involved in bFGF-induced DNA synthesis in cSMC. Thus, our data suggest that, lovastatin possibly affects the dephosphorylation processes of PKC and MAPK by inhibition of PP-1/PP-2A protein phosphatases which are involved in the bFGF-induced mitogenesis in cSMC.

Differences in the effects of HMG-CoA reductase inhibitors on proliferation and viability of smooth muscle cells in culture.

We investigated the influence of lovastatin, simvastatin and pravastatin on proliferation and viability of vascular smooth muscle cells (SMC) in vitro and studied the effects of lovastatin on a mouse SMC line transgenic for a temperature-sensitive mutant of SV40 large T antigen (TAg), known to inhibit the function of p53 and pRb family members. We found that lovastatin and simvastatin inhibited cell proliferation by provoking G0/G1 phase arrest with concomitant depression of the proliferation antigen Ki-67/MIB-1. Lovastatin at high concentrations of 20 micromol/l caused cell death in the presence of serum but not under serum starved conditions, which was verified on the basis of increased DNA strand breaks, decreased DNA content and morphological alterations seen by electron microscopy. Cell death was also found for simvastatin, whereas pravastatin did not exhibit antiproliferative or cytotoxic effects. Mouse SMC transgenic for TAg did not show any impaired sensitivity to the antiproliferative and cell death inducing effect of lovastatin, but both effects could be antagonized by the supplementation of mevalonate. The data indicate that antiproliferative and cytotoxic effects of lovastatin are caused by the using up of products of mevalonate metabolism and do not require the presence of p53 or pRb.

Early activation and proliferation of T cells in simian immunodeficiency virus-infected rhesus monkeys.

To longitudinally determine T cell activation and turnover in early simian immunodeficiency virus (SIV) infection of macaques, immunological and virological parameters were monitored in 10 SIV-infected animals starting before infection until 40 weeks postinfection (wpi). Lymphocyte subsets in blood and lymph nodes (LNs) were characterized by three-color flow cytometry for expression of markers of activation, proliferation, and differentiation. As early as 1 wpi, CD69 expression was upregulated both on CD4+ and CD8+ T cells, indicative of an early activation of these cells. Whereas this activation led to increased proliferation, determined by expression of Ki-67, and absolute numbers of CD8+ T cells, CD4+ T cells showed a decreased expression of Ki-67 and reduced counts in blood at 2 wpi. Later, the percentage of Ki-67-expressing CD4+ T cells in blood and LNs increased again above preinfection levels in most animals but remained low in two monkeys progressing to AIDS. These findings suggest that T cells are activated after SIV infection, leading to increased T cell proliferation already in the early asymptomatic phase. In addition, we found a correlation between the capacity to regenerate CD4+ T cells by peripheral proliferation and the disease course. Moreover, our data indicate that the increased peripheral T cell proliferation during immunodeficiency virus infection is probably not caused by the effort of the immune system to maintain T cell homeostasis but may be a reflection of the ongoing immune response against the virus.

The pH-dependent role of superoxide in riboflavin-catalyzed photooxidation of 8-oxo-7,8-dihydroguanosine.

[reaction: see text]. The riboflavin-catalyzed photooxidation of 2',3',5'-tri-O-acetyl-8-oxo-7,8-dihydroguanosine generates a radical intermediate that is competitively trapped by H(2)O, O2(-)(*), or O(2). The products of H(2)O trapping have been previously described as the spiroiminodihydantoin (pH >or= 7) and iminoallantoin/guanidinohydantoin (pH < 7) nucleosides. Trapping by O2(-)(*) leads to the oxaluric acid (pH or= 8.6) pathways (R' ', R' ' = H or 2,3,5-tri-O-Ac-ribofuranosyl). The pH-dependent role of superoxide was probed using Mn-SOD and compared to guanosine and 8-methoxyguanosine photooxidation.

Characterization of spiroiminodihydantoin as a product of one-electron oxidation of 8-Oxo-7,8-dihydroguanosine.

[reaction: see text] Further oxidation of the common DNA lesion 8-oxo-7,8-dihydroguanosine by one-electron oxidants such as IrCl6(2-), Fe(CN)6(3-), or SO4-* leads to two major products, depending upon reaction conditions. In nucleosides at pH 7, 22 degrees C, the principal product is shown herein to be a spiroiminodihydantoin nucleoside, as a diastereomeric mixture, that can be characterized by NMR, ESI-MS/MS, and independent synthesis.

DNA-ploidy, G2M-fractions and prognosis of stages B and C prostate carcinoma.

Paraffin embedded tissue of 49 stage C and 27 stage B prostate adenocarcinomas was investigated by flow cytometry. All patients were treated by radical prostatectomy with pelvic lymphadenectomy and followed up for 5-10 years. The tumour was separated from the benign tissue to increase the proportion of tumour cells. Ten stage C and seven stage B carcinomas had to be excluded because of poor fixation. Six of the 39 (15%) stage C and 1/20 (5%) stage B carcinomas were aneuploid. Cell cycle analysis was done with correction for sliced nuclei and background subtraction. The threshold between carcinomas with low and with increased ("tetraploid") G2M-fraction was determined by comparing carcinomas with and without tumour progression. Sixty-seven percent of the patients with non-euploid stage C carcinomas and 11% of those with euploid carcinomas suffered from tumour progression (P < 0.01). The respective values for the stage B carcinomas were 67% and 6% (P < 0.01). These results demonstrate the strong prognostic impact of DNA-ploidy and G2M-fractions for each individual patient.

Vaginal clear cell carcinoma in a young patient with ectopic termination of the left ureter in the vagina.

The association of clear cell adenocarcinoma of the vagina and vaginal adenosis with prenatal exposure to diethylstilbestrol (DES) is well-documented in the United States. In Europe, however, DES was never used in the therapy of threatened abortion and, therefore, clear cell adenocarcinoma and vaginal adenosis remained rare diseases. We report on the clinical and pathological features of a case of clear cell adenocarcinoma of the upper vagina in a 17-year-old German girl, who had a history of hypoplasia of the left kidney with an ectopic termination of the ureter in the upper vagina, removed surgically 2 years before. No previous report of a similar coincidence of vaginal clear cell carcinoma and a congenital disorder of the genitourinary tract exists. Congenital anomaly of the ureter interfering with the development and the differentiation of the distal Müllerian tract and its epithelium might have provided a similar histological basis for carcinogenesis in our patient to that in those provided exposed to DES.

The cytomorphological spectrum of mantle cell lymphoma is reflected by distinct biological features.

Mantle cell (centrocytic) non-Hodgkin's lymphoma (MCL) is a malignant tumour with unique biological features. The pathogenesis of MCL seems to be strongly associated with aberrant function of the cell cycle. 110 cases of MCL have been analysed for their cytomorphological features, mitotic and proliferation indices, bcl-1 rearrangements, p53 expression patterns and DNA content by both interphase cytogenetic as well as DNA flow cytometric analyses. According to cytomorphology, three subtypes were recognized: a common, a lymphoblastoid and a pleomorphic variant of MCL. Blastic MCL subtypes were characterized by distinctly elevated mitotic and proliferation indices, frequent bcl-1 rearrangements at the MTC locus, and overexpression of p53. The most interesting finding, however, was a striking tendency of blastoid MCL subtypes to harbour chromosome numbers in the tetraploid range, a feature clearly separating these neoplasms from other types of B-cell NHL and possibly being related to its unphysiological expression of cyclin D1. Although characterised by a uniform immunophenotype and common biological background, MCL shows a broad spectrum of morphological features ranging from small cell to blastic types, and this spectrum is mirrored by distinct biological features.

Prognostic relevance of p53 in node negative breast cancer.

In a retrospective study, immunohistochemical determinations of p53 were performed on paraffinised tissue sections of 243 patients with node negative breast cancer. These patients were primary treated in the years 1980-1986 at the UFK-Würzburg. A complete follow up could be performed in 92% of all cases. The median follow up is at 102 month. The results have been correlated to other prognostic criteria and to the clinical course of the patients. In 77 of the 243 cases a positive immunohistochemical staining for p53 (31.7%) could be found. In 42 (17.3%) cancer specimens the p53 expression was over 5%. A significant correlation was found between p53 and tumour size (p = 0.05), ploidy (p < 0.001) and dynamic parameters of the cell cycle (S-phase-fraction, MIB1: p < 0.001). In univariate and multivariate analysis the expression of p53 did not effect disease-free or over-all survival of patients with node negative breast cancer.

Histological changes in the colonic mucosa following irrigation with short-chain fatty acids.

OBJECTIVES: Short-chain fatty acids (SCFAs) derived from bacterial fermentation of complex carbohydrates are preferred luminal nutrients of the colonic mucosa. Starvation of colonocytes through lack or impaired metabolism of luminal SCFAs may be a cofactor in the pathogenesis of ulcerative colitis. DESIGN: A detailed histological evaluation of colonic biopsy specimens was performed in patients with active distal ulcerative colitis who were treated with rectal enemas containing a mixture of SCFAs, n-butyrate alone or saline placebo. Together with light microscopic parameters of mucosal inflammation, the pattern of crypt cell proliferation (proliferating cell nuclear antigen) and the mucosal activity of factor XIII were assessed. RESULTS: Butyrate reduced the density of polymorphonuclear leucocytes in the lamina propria (4 weeks: P = 0.063; 8 weeks: P = 0.091); other inflammatory parameters remained unchanged. Both butyrate and the SCFA mixture reduced significantly the number of proliferating cells in the upper 40% of crypts. Tissue factor XIII activity in active ulcerative colitis was significantly lower than in mucosa from normal colons; however, it was not affected by SCFA or butyrate irrigation. CONCLUSION: SCFAs and butyrate have a more marked effect on crypt cell proliferation than on parameters of inflammation in patients with active ulcerative colitis.

DNA modification promoted by water-soluble nickel(II) salen complexes: a switch to DNA alkylation.

Reaction of a 17-base hairpin-forming oligonucleotide with [N,N'-bis(salicylaldehyde)-meso-1,2-bis(4- trimethylaminophenyl)ethylenediimino]nickel(II) perchlorate, 2, and KHSO5 produced two types of high molecular weight products, an alkaline-labile species and a nonalkaline-labile species, which co-migrated on gel electrophoresis. Upon treatment with piperidine, the base-labile derivative led to strand scission products only at accessible guanine residues that were not part of a Watson-Crick duplex. The formation of higher molecular weight species is proposed to occur via a highly reactive ligand-centered radical acting as a DNA alkylating agent.

Automated ST-segment monitoring.

Automated ST-segment monitoring expands the ability of the anesthesiologist to detect ischemia intraoperatively. However, improvements in technology are required before significant advances in patient care and safety can be ascribed to such monitoring. Until then, the clinician must abide by the adage that monitoring is an extension of the physical examination and that data must therefore be interpreted in the context of the total clinical picture presented by the patient.

[Fatty liver in adult celiac disease]. / Fettleber bei adulter Sprue.

HISTORY AND ADMISSION FINDINGS: A 31-year-old woman was admitted because of heptomegaly and abnormal liver functions. For years she had suffered from diarrhoea but its cause had never been elucidated. She was underweight and had mild ankle edema. The liver margin was palpable at 20 cm below the midcostal margin, but the abdominal examination was otherwise unremarkable. INVESTIGATIONS: Sonography revealed a very large fatty liver. Biopsy showed fatty infiltration of nearly all the hepatocytes, without significant inflammation and fibrosis. Small-intestinal biopsy showed the typical histology of coeliac disease. Laboratory tests indicated abnormal liver function with increased transaminases, alkaline phosphatase, GPT and LDH, but no sign of inflammatory aetiology. These findings suggested that the liver changes were due to the coeliac disease. TREATMENT AND COURSE: After the patient had been put on a gluten-free diet the diarrhoea stopped and she started to gain weight. The liver function tests briefly became worse, but over the following 6 weeks normalized completely. The patient gained 5 kg in the subsequent 18 months and the liver became sonographically normal. The small-intestinal biopsy now showed merely discrete villar atrophy. CONCLUSION: Coeliac disease should be considered in any case of fatty liver of unknown cause. Strict gluten-free dietary treatment of the underlying cause can quickly lead to complete regression of the hepatic changes.

[Immunity to diphtheria of African guest workers and students]. / Diphtherieimmunität afrikanischer Gastarbeiter und Studenten.

This study investigated the immuno-protective diphtheria antitoxin titres of 38 guest workers from Mozambique and 44 students from Cameroon 18 to 35 years of age. Two methods were used to analyse the sera: the cell culture method and the indirect haemagglutination test. The results of both methods were comparable. Approximately 69% of the guest workers from Mozambique showed protective diphtheria antitoxin levels (> or = 0.1 IE/ml), 24% had a boosterrequiring basic immunity (> or = 0.01-0.09 IE/ml), whereas 7% showed no protective diphtheria antitoxin levels. This compared with 46, 35 and 19% respectively among the students from Cameroon.