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Biomedical subjects

R Flückiger

Publications and source records attributed to R Flückiger.

At least 19 recordsLinked to original sources
PubMed2001

Comparative biology of aging in birds: an update.

The long life spans and slow aging rates of birds relative to mammals are paradoxical in view of birds' high metabolic rates, body temperatures and blood glucose levels, all of which are predicted to be liabilities by current biochemical theories of aging. Available avian life-table data show that most birds undergo rapid to slow "gradual" senescence. Some seabird species exhibit extremely slow age-related declines in both survival and reproductive output, and even increase reproductive success as they get older. Slow avian senescence is thought to be coupled evolutionarily with delayed maturity and low annual fecundity. Recent research in our lab and others supports the hypothesis that birds have special adaptations for preventing age-related tissue damage caused by reactive oxygen species (ROS) and advanced glycosylation endproducts, or AGEs, as well as an unusual capacity for neurogeneration in brain. Much of this work is in its early stages, however, and reliable biomarkers for comparing avian and mammalian aging need more thorough development.

Aging↗
PubMed2000

Inhibition of translation initiation mediates the anticancer effect of the n-3 polyunsaturated fatty acid eicosapentaenoic acid.

Eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid that is abundant in the fish-based diets of populations that exhibit a remarkably low incidence of cancer, exerts anticancer activity in vitro and in animal models of experimental cancer. Here we define the molecular basis for the anticancer effects of EPA. EPA inhibits cell division by inhibiting translation initiation. This is a consequence of the ability of EPA to release Ca2+ from intracellular stores while inhibiting their refilling via capacitative Ca2+ influx that results in partial emptying of intracellular Ca2+ stores and thereby activation of protein kinase R. Protein kinase R phosphorylates and inhibits eukaryotic initiation factor 2alpha, resulting in inhibition of protein synthesis at the level of translation initiation, preferentially reducing the synthesis and expression of growth-regulatory proteins, including G1 cyclins, and causes cell cycle arrest in G1. In a KLN-205 squamous cell carcinoma mouse model, daily oral administration of EPA resulted in a significant reduction of tumor size and expression of cyclin D1 in the tumor tissues. Furthermore, EPA-treated tumors showed a significant increase in the proportion of diploid cells, indicative of cell cycle arrest in G0-G1, and a significant reduction of malignant hypertetraploid cells. These results characterize EPA as a member of an emerging new class of anticancer compounds that inhibit translation initiaton.

3T3 Cells↗
PubMed2000

Molecular basis for a link between complement and the vascular complications of diabetes.

Activated terminal complement proteins C5b to C9 form the membrane attack complex (MAC) pore. Insertion of the MAC into endothelial cell membranes causes the release of growth factors that stimulate tissue growth and proliferation. The complement regulatory membrane protein CD59 restricts MAC formation. Because increased cell proliferation characterizes the major chronic vascular complications of human diabetes and because increased glucose levels in diabetes cause protein glycation and impairment of protein function, we investigated whether glycation could inhibit CD59. Glycation-inactivation of CD59 would cause increased MAC deposition and MAC-stimulated cell proliferation. Here, we report that (i) human CD59 is glycated in vivo, (ii) glycated human CD59 loses its MAC-inhibitory function, and (iii) inactivation of CD59 increases MAC-induced growth factor release from endothelial cells. We demonstrate by site-directed mutagenesis that residues K41 and H44 form a preferential glycation motif in human CD59. The presence of this glycation motif in human CD59, but not in CD59 of other species, may help explain the distinct propensity of humans to develop vascular proliferative complications of diabetes.

Amino Acid Sequence↗
PubMed1998

Depletion of intracellular Ca2+ stores, phosphorylation of eIF2alpha, and sustained inhibition of translation initiation mediate the anticancer effects of clotrimazole.

Regulation of translation initiation plays a critical role in the control of cell growth and division in eukaryotic cells. Translation of many growth regulatory proteins including cyclins depends critically on translation initiation factors because their mRNAs are translated inefficiently. We report that clotrimazole, a potent antiproliferative agent both in vitro and in vivo, inhibits cell growth by interfering with translation initiation. In particular, clotrimazole causes a sustained depletion of intracellular Ca2+ stores, which results in activation of PKR, phosphorylation of eIF2alpha, and thereby in inhibition of protein synthesis at the level of translation initiation. Consequently, clotrimazole preferentially decreases the expression of the growth promoting proteins cyclin A, E and D1, resulting in inhibition of cyclin-dependent kinase activity and blockage of cell cycle in G1.

3T3 Cells↗
PubMed1998

[Duplication cyst of the stomach antrum as the cause of an acute gastric emptying disorder in an adult].

HISTORY AND CLINICAL FINDINGS: A 35-year old woman without previous history of gastrointestinal complaints developed increasing upper abdominal pain with nausea and postprandial vomiting over 2 days during which she had been unable to take any food. She had no fever; her general physical condition was slightly reduced. While her abdomen felt soft on palpation, she had epigastric pain on pressure but no resistance to palpation. INVESTIGATIONS: Blood picture and routine laboratory tests were unremarkable. Plain film of the abdomen demonstrated marked gastric retention. Abdominal ultrasound showed an invagination in the gastric antrum suggesting a layering phenomenon. Gastroscopy revealed a submucosal tumour-like lesion with central ulceration which obstructed gastric exit. TREATMENT AND COURSE: After conclusion of the diagnostic tests on the first hospital day partial gastric resection (Billroth I) was performed as, in the absence of any surrounding reaction, a leiomyoma had been suspected. The further course was without complication and she was discharged on the 13th hospital day. The surgical specimen revealed a duplication cyst of the gastric antrum. CONCLUSION: (Endo)sonography, computed tomography and endoscopy make it possible to diagnose duplication cyst, as long as it is included in the differential diagnosis of acute abdomen in an adult. Emergency resection of the cyst is indicated because of the acute nature of the symptoms. But even in less urgent cases or as an incidental finding it is the treatment of choice.

Abdomen, Acute↗
PubMed1998

[Diverticulitis of the cecum and ascending colon].

Right colon diverticulitis, representing 1-3.6% of cases of diverticular disease is an uncommon cause of right lower quadrant pain. Its presentation is difficult to distinguish from acute appendicitis. Patients are between 35 and 50 years old, have a history of 2-3 days of abdominal pain and few gastrointestinal symptoms. The diagnosis is best confirmed by computed tomography and colonoscopy. Conservative treatment is justified in uncomplicated disease, whereas perforations, abcesses and inflammatory tumors require resection. We describe the cases of six patients treated at our institution from 1991 to 1996. Presentation, geographic variations, diagnostic procedures and management are discussed.

Abdomen, Acute↗
PubMed1996

The catalysis of redox cycling by pyrroloquinoline quinone (PQQ), PQQ derivatives, and isomers and the specificity of inhibitors.

Pyrroloquinoline quinone (PQQ) is a widely distributed redox-active cofactor and essential nutrient. For its detection in protein-free ultrafiltrates or dialysates, a highly sensitive amplification assay was developed on the basis of PQQ's ability to catalyze redox cycling at pH 10 in the presence of excess glycine, oxygen, and nitro blue tetrazolium. Herein, we examine the propensities of PQQ, PQQ triester, and its various isomers, and certain PQQ triester derivatives, to catalyze glycine-fueled redox cycling and show that PQQ is the most capable of catalyzing redox cycling. Furthermore, PQQ has a unique pattern of inhibition induced by a series of PQQ antagonists of different potencies. The data indicate that putative PQQ from a biological sample, separated by HPLC and detected by the glycine-fueled redox-cycling assay, can be further identified as PQQ based on the profile of inhibition it displays with the antagonists such as those employed in this study. The methodology presented here should facilitate the specific detection of PQQ in biological samples.

Animals↗
PubMed1996

[Tumor of the gastrointestinal autonomic nervous system (GAN-tumor or plexus sarcoma)].

GAN-tumors or plexosarcomas, first described by Herrera et al. in 1984, are uncommon neurogenic stromal spindle cell tumors of the intestinal tract mainly located in the stomach and the small intestine. The distinctive immunohistochemical pattern is the positive staining for vimentin and neuron-specific-enolase. Ultrastructural features are neuron-like cells with interdigitating cytoplasmic processes, dense-core neurosecretory granules, the lack of basement membranes and the presence of interstitial skeinoid fibers. Pain, chronic and acute bleeding are the most frequent but not specific symptoms and the diagnostic delay is reflected by a large average diameter of these tumors. For even smaller tumors and those with a low mitotic rate may metastasize, GAN-tumors must be considered malignant and need a radical surgical resection.

Aged↗
PubMed1996

[True aneurysm of the femoral profunda artery].

Aneurysms of arteriosclerotic origin in the profunda femoris artery are rare. Twenty-nine cases were reported in the world literature. In addition two own cases are presented. This total of 31 patients with 34 true aneurysms of the profunda femoris artery is analyzed. The risk of complications such as rupture, thrombosis and embolization amounts to above 50% and seems to be higher than in popliteal or femoral aneurysms. Acute dilatation and rupture occurred in 34.5%. Nearly half of the patients suffered from one or more additional arterial aneurysms. This number emphasizes the need of a complete angiological investigation in patients with aneurysms of the profunda femoris artery. The treatment of choice consists of aneurysm resection and reconstruction by an autologous vein bypass. In selected cases with patent superficial femoral artery, a simple resection may be sufficient.

Aged↗
PubMed1995

[Sigmoid volvulus--clinical, radiological and therapeutic aspects of rare disease].

Volvulus of the sigmoid colon is a common cause of colonic obstruction in many parts of the world, mainly in developing countries and in Scandinavia, but is rare in the Western Hemisphere, where it occurs in elderly patients who often have serious coexisting diseases, especially cardiovascular and neuropsychiatric disorders. Although many patients present with the typical triad of abdominal pain, distension and constipation, the disease is correctly diagnosed only in about 62%. Diagnostic delay is due in part to the relative rarity of the illness, in part to the variety of the clinical and radiologic presentation, and it might contribute to the high mortality. Treatment consists in endoscopic decompression, whenever there are no compromised intestines, followed by an elective, sigmoid resection in otherwise healthy patients, because the risk of recurrence is high after nonoperative decompression alone. Hartmann's procedure is the safest procedure in patients with ischemic necrosis of the sigmoid colon. The site of primary resection and anastomosis with viable bowel remains controversial. Knowledge of sigmoid volvulus is of general interest with respect to the growing number of elderly patients, especially those residing in nursing homes and psychiatric institutions.

Aged↗
PubMed1994

Oral hairy leukoplakia in a patient with ulcerative colitis.

A 30-year-old man with ulcerative colitis developed oral hairy leukoplakia (OHL). Serological examination for human immunodeficiency virus (HIV)-1 and HIV-2 infection showed no abnormalities. Biopsy specimen of the lateral tongue showed ballooned prickle cells, and electron microscopy revealed herpes-type viruses. Immunologic investigation of the patient showed a marked decrease in T-helper cells as a result of immunosuppressive regimen. The present report appears to be the first well-documented case of OHL in an HIV-negative patient with ulcerative colitis. OHL may be a marker for severe immunosuppression but is not necessarily associated with HIV infection. Patients with iatrogenic immunosuppression should be monitored for OHL. Concerning the marked decrease in T-helper cells in this case, the presence of OHL may imply the examination of T-lymphocyte subsets in patients such as HIV-infected individuals or in organ transplant recipients.

Adult↗
PubMed1994

Recurrent pyogenic granuloma with satellitosis--a localized variant of bacillary angiomatosis?

A 27-year-old male patient had recurrent pyogenic granuloma with satellitosis. Histologically, Warthin-Starry staining of the lesions revealed clumps of dark bacilli as found in patients with bacillary angiomatosis. IgG antibodies against Bartonella (Rochalimaea) henselae were elevated as shown by an indirect immunofluorescence assay. The patient did not present an obvious risk for HIV infection or immunosuppression, and no antibodies against HIV-1 and HIV-2 were found. Recurrent pyogenic granuloma with satellitosis may be a localized variant of bacillary angiomatosis.

Adult↗
PubMed1993

Characterization of the glycine-dependent redox-cycling activity in animal fluids and tissues using specific inhibitors and activators: evidence for presence of PQQ.

Pyrroloquinoline quinone, a redox cofactor first isolated from bacteria, efficiently catalyzes the nonenzymatic oxidation of glycine in the presence of nitroblue tetrazolium. We report that certain metallic cations and heterocyclic aromatic cations, like the N-methyl phenazonium cation and aryl-iodonium compounds, strongly and specifically inhibit this redoxcycling activity. The inhibition by metal cations is reversed by Tiron and that of the aromatic cations by Tiron and thyroxine. These inhibitors and activators affect authentic PQQ and the redox-activity of putative PQQ isolated from biological sources in a similar manner. This indicates that pyrroloquinoline quinone occurs naturally in animal tissues and fluids.

Animals↗
PubMed1993

Oral manifestations in HIV-infected patients: diagnosis and management.

Oral lesions have been observed since the beginning of the AIDS epidemic. The number of HIV-infected patients is still increasing, especially in the heterosexual population. Oral diseases in HIV-infected patients are often more difficult to diagnose because the clinical presentations may differ from the same diseases in HIV-negative patients. HIV-associated oral lesions have diagnostic, prognostic, and therapeutic impact. Approximately 10% of the HIV-infected population will have oral manifestations as a first sign of their disease. In HIV-infected men oral hairy leukoplakia and oral candidiasis are useful markers for disease progression. This article summarizes the oral manifestations and the management of oral health in persons with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Keratosis extremitatum (Greither's disease): clinical features, histology, ultrastructure.

Keratosis palmoplantaris progrediens et transgrediens (Greither's disease) was first described by Greither in 1952. The inheritance pattern is autosomal dominant with variable expression. The clinical manifestation is characterized by diffuse palmoplantar keratoderma associated with hyperhidrosis and progressive extension of keratoderma to the dorsum of the hands and feet. In addition, hyperkeratotic plaques may occur on the elbows and knees. We describe a 44-year-old patient with typical features of Greither's disease. Immunohistologic and ultrastructural investigations are presented.

Achilles Tendon↗