Biomedical subjects

Frank Sommer

Publications and source records attributed to Frank Sommer.

24 records · Page 2Linked to original sources

PubMed2003

Differential production of macrophage inflammatory protein 1gamma (MIP-1gamma), lymphotactin, and MIP-2 by CD4(+) Th subsets polarized in vitro and in vivo.

Due to differential expression of chemokine receptors, the Th1 and Th2 subsets of CD4(+) T cells differ in their migratory responses to chemokines. These differences in the migration patterns are likely to play a role in the initiation and regulation of Th1 and Th2 immune responses, inflammatory processes, and T-cell-mediated pathology. In the present study we evaluated the role of activated Th cells as producers of chemokines. Three different sources of murine Th cells were used, i.e., long-term-cultured Th1 and Th2 cell clones, Th1 and Th2 cells differentiated from naïve CD4(+) spleen and lymph node cells in vitro, and Th1 and Th2 subsets polarized in vivo using a murine experimental Leishmania major infection model. Following stimulation with anti-CD3, macrophage inflammatory protein 1gamma (MIP-1gamma) and lymphotactin were produced selectively by Th1 cells but not by Th2 cells. In contrast, only Th2 cells produced MIP-2. The possible biological relevance of these data was substantiated by the finding that in vivo-polarized Th1 cells, but not Th2 cells, produced MIP-1gamma and lymphotactin while in vivo-polarized Th2 cells secreted MIP-2. The above data demonstrate that Th1 and Th2 cells differ in their ability to produce chemokines, suggesting that Th1 and Th2 subsets differentially contribute to recruitment of cells into inflammatory foci.

Animals↗

PubMed2002

Nitric oxide pathways in human bladder carcinoma. The distribution of nitric oxide synthases, soluble guanylyl cyclase, cyclic guanosine monophosphate, and nitrotyrosine.

BACKGROUND: Nitric oxide (NO) is produced by a group of synthase enzymes (NOS). By means of different pathways, NO exerts several functions in benign and malignant human bladder tissues. The current paper describes the NO/guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) and the NO/oxidative pathways in human bladder tissues. METHODS: Bladder carcinoma tissues were collected from 18 patients by transurethral resection procedures. Normal benign vesical tissue specimens from a further eight patients with benign diseases served as controls. Immunohistochemistry was conducted for localization of sGC, cGMP, and nitrotyrosine in benign and malignant vesical tissues, evaluating two-three tissue sections per patient. RESULTS: Positive immunolabeling for sGC and cGMP was detected in vascular endothelial cells of normal and malignant vesical tissues. Those signals were most intense in bladder carcinoma tissues. Immunolabeling for sGC and cGMP was also detected in normal urothelial cells. In bladder carcinoma cells, a heterogeneous immunolabeling for sGC and cGMP was seen, with a wide spectrum of signal intensity. Positive immunostaining for sGC and cGMP was also observed in stromal round cells in benign and malignant bladder tissues. Immunolabeling for nitrotyrosine was mainly observed in endothelial cells, with a much stronger immunolabeling in bladder carcinoma tissues compared to normal benign controls. A weak immunolabeling for nitrotyrosine was also observed in bladder carcinoma cells. Normal urothelial cells did not show such nitrotyrosine expression. CONCLUSIONS: The current report provides evidences that NO play several roles through different pathways in benign and malignant vesical tissues. The influences generated by NO molecules can be divided into cGMP-mediated effects (those resulting from the NO/sGC/cGMP pathway) and non-cGMP-mediated effects (those resulting from the NO/oxidative pathway). Increased angiogenesis is a cGMP-mediated effect, while nitrotyrosine production is a non cGMP-mediated oxidative effect. Such an NO/oxidative pathway is observed more often in bladder carcinoma.

Aged↗

PubMed2002

Dysregulated T helper cell differentiation in the absence of interferon regulatory factor 4.

Certain IFN regulatory factor (IRF) transcription factors indirectly influence T helper (Th) cell differentiation by regulating the production of IL-12. Here, we show that IRF4 directly regulates Th cell differentiation in vitro and in vivo during murine leishmaniasis. In the absence of IRF4, IL-12-induced Th1 cell differentiation was compromised, while IL-4 failed to induce Th2 cell differentiation. Instead, IL-4 tended to induce Th1 cells, defined by production of IFN-gamma and TNF. Although early IL-4 signaling was normal in IRF4(-/-) Th cells, the protein GATA-3, a transcription factor critical for Th2 development, was not up-regulated following IL-4 treatment. Retroviral overexpression of GATA-3 rescued Th2 differentiation. Therefore, IRF4 deficiency manifests itself as severely dysregulated Th cell differentiation.

Animals↗

PubMed2002

Unsaturated dodecahedranes--in quest of the C20H14 1,4,16-triene and C20H12 1,4,10(14),16-tetraene, and their cations and anions.

The highly pyramidal, highly strained 1,4,16-dodecahedratriene (4) and C20H12 1,4,10(14),16-dodecahedratetraene (5) are cage olefins with an intriguing "inner life". For 5 DFT calculations give information about the energetic and geometrical consequences of one-/two-electron oxidation and reduction. Attempts to prepare 4 and 5 through thermal retro[2+2]/[4+2]cycloaddition strategies proved unsuccessful. Still, the C20H14/C20H12 cage cations and anions are liberated upon electron impact or gas-discharge ionization of their thermally extremely stable tris-/tetrakisanthraceno-anellated derivatives. Mass-selection (photoelectron (PE) characterization) of the anions failed, however, due to the very small anion intensity, the preferential formation of hydrogen-poor ions, and minor cage disruption.

Journal Article↗

PubMed2002

Cycling and penile oxygen pressure: the type of saddle matters.

OBJECTIVES: Temporary genital numbness is a common side effect of long-distance cycling; cases of impotence have even been reported. Recent reports have shown that perineal compression leads to a decrease in penile blood flow. Reduced oxygen tension leads to penile fibrosis, which works counterproductively to the achievement of an erection. The shape of the bicycle saddle could be a factor affecting penile perfusion. The aim of this study is to find out the influence of different saddle designs on penile perfusion. MATERIAL AND METHODS: In 20 healthy athletic young men (mean age 26.8 years, range 21-31 years) without history of erectile dysfunction, transcutaneous oxygen pressure (PtcO2), which correlates with arterial and tissue PO2, was measured at the glans of the penis using a transcutaneous measurement device. All men were measured in a standing position before cycling, then during cycling in a seated position on a stationary bicycle. Four different bike saddle designs were used: (A) narrow heavily padded seat; (B) narrow seat with medium padding and a V-shaped groove in the saddle nose ("body geometry"); (C) wide unpadded leather seat; (D) women's special wide seat with medium padding and no saddle nose. RESULTS: During cycling in all seats a decrease in penile oxygen pressure could be observed, reflecting perineal compression. But the differences were unexpected: seat (A) mean PtcO2 11.8 mmHg, decrease in initial oxygen pressure 82.4%; seat (B) mean PtcO2 20.8 mmHg, decrease in initial oxygen pressure 72.4%; seat (C) mean PtcO2 25.3 mmHg, decrease in initial oxygen pressure 63.6%; seat (D) mean PtcO2 62.3 mmHg, decrease in initial oxygen pressure 20.3%. CONCLUSIONS: Cycling in a seated position leads to a compression of perineal arteries with a consequent significant decrease in penile perfusion. But, there are unexpected differences between different saddle types. It was possible to demonstrate that the most important factor in safeguarding penile perfusion is not the amount of padding, but rather a saddle width which prevents sufficiently the compression of the perineal arteries.

Adult↗

PubMed2002

Vardenafil Bayer Yakuhin.

Bayer is developing vardenafil, an orally active phosphodiesterase (PDE) 5 inhibitor for the potential treatment of erectile dysfunction (ED) [314382]. NDAs were filed in September 2001 in the US and Mexico [423096], and vardenafil was submitted for Canadian approval in October 2001. As of November 2001, Bayer was expecting a response from the FDA in the second half of 2002 [429499]; the EMEA accepted a filing in January 2002, following a December 2001 submission [438163]. By October 2000, phase III trials were underway in Japan [384751] and by December 2001, a Japanese NDA had been filed; at the same time an application was filed in South Africa [426526], [433060]. At this time Japanese launch was expected in 2003 [434758]. By February 2001, Bayer was also investigating a nasal formulation of vardenafil for the potential treatment of erectile dysfunction [397608]. In November 2001, Bayer and GlaxoSmithKline signed a worldwide copromotion agreement for vardenafil, under which Bayer was to be responsible for all regulatory work required to obtain approval [429499]. In February 1999, Lehman Brothers predicted a 10% probability that vardenafil would reach the market, with launch in 2002. Peak Japanese sales of US$600 million were predicted for 2014 [319225]. In May 2000, Bayer predicted peak sales of Euro900 million [397137]. In July 2001, Lehman Brothers predicted a 75% chance that vardenafil would reach the market, and forecast peak sales of US $0.85 billion worldwide; the analyst also speculated that Bayer would seek a comarketing partner [414766].

3',5'-Cyclic-GMP Phosphodiesterases↗