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In the late 1950s, Patrick C. Steptoe, a British gynecologist, established contact with Palmer of Paris and Frangenheim of Wuppertal, Germany, and studied laparoscopic technique under the tutelage of these pioneers. Despite the negative attitude among his colleagues, Steptoe soon became one of the most innovative researchers in the field of abdominal endoscopy, particularly laparoscopic sterilization. In the late 1960s, Steptoe began working with Robert Edwards, an embryologist, and launched an in-vitro fertilization project obtaining eggs by means of laparoscopy. Both researchers experienced years of frustration, disappointment, ethical and scientific criticism as well as a difficult relationship with the mass media. Finally, in July 1978, Louise Brown, the first test-tube baby, was born in England.
Like many of his colleagues in the 1950s and 1960s, Patrick Christopher Steptoe (1913-1988), a gynecologist in Oldham, Great Britain, was concerned about the number of unnecessary laparotomies. Unfortunately, the Oldham group of hospitals was not a university clinic and Steptoe had scanty opportunity to develop his own research. In the late 1950s, he searched the medical literature for an alternative form of examination and came across publications about Decker's culdoscopy, the vaginal approach to view the abdomen. Since this method was not widespread in England, Steptoe, in 1958, went to Montreal, Boston, and New York in order to observe and learn the practical use of culdoscopy. However, Steptoe left America disappointed.
In the United States, culdoscopy (a vaginal approach to view the abdomen) replaced laparoscopy for about 20 years, circa 1950-1970. In contrast to many of his colleagues, Hans Frangenheim of Wuppertal, Germany, was not satisfied with culdoscopy and turned to an abdominal approach. Frangenheim began publishing his experiences with gynecological laparoscopy in 1958 and stressed technical improvements. He constructed a CO2 insufflator, wrote the first book on gynecological endoscopy, and introduced "cold light" into laparoscopy. Frangenheim strongly stimulated the rise of gynecological laparoscopy in Europe in the 1960s and later.
Raoul Palmer, World War II, and transabdominal coelioscopy : laparoscopy extends into gynecology
(1997)
This profile of laparoscopic pioneers between the world wars "spotlights" Heinz Kalk, a German surgeon, and John C. Ruddock, an American internist. Social, political and economic upheavals characterized the decades between World War I and World War II and, along with geographic and communication restraints, permitted the concept of laparoscopy to develop differently in separate settings.
The traditional gap between surgeons and internists was much wider 100 years ago than nowadays. At the beginning of the twentieth century, neither group was particularly open to the idea of scholarly exchange. In this respect, both early pioneers of laparoscopy, Georg Kelling (1866–1945, a German surgeon of Dresden, and Hans Christian Jacobaeus (1879–1937), an internist from Stockholm, Sweden, were interesting exceptions...
At the end of the 20th century, access to information provided by the World Wide Web (WWW) is changing as never before. The fast availability of current medical literature and the availability of tools for easy access to information, as well as for the easy production of information, have confronted research physicians, scholars, and students with new kinds of problems, many of which concern us personally. Quality control, difficulty establishing basic citation components, lack of standard guidelines for citing, as well as the short lifetime of Internet addresses concern us deeply. Some of these problems could be solved by the concept of an "Online-Library of Medicine" presented in the following paper. Since, however, at the present time there are no good answers to the problems regarding citing Internet-based sources, a Web surfer must keep in his or her mind the motto “caveat lector” (let the reader beware) - or, rather, in the spirit of our time: click c@refully before you cite.
Erich Mühe and the rejection of laparoscopic cholecystectomy (1985) : a surgeon ahead of his time
(1998)
During the early 1980s, news of Semm's laparoscopic appendectomy was rippling through German medical circles. Erich Mühe, fascinated by Semm's technique and spurred by successes of the Erlangen endoscopists, came up with the idea of laparoscopic removal of gallstones. In 1984, Mühe had already worked out the details of an operative laparoscope, the “Galloscope,” and on September 12, 1985, he carried out the first laparoscopic cholecystectomy. Later, he modified his technique and operated through a trocar sleeve. Finally, he designed an “open laparoscope” with a circular light. By March 1987, Mühe had conducted 97 endoscopic gallbladder removals. He published information about his technique at the Congress of the German Surgical Society (April 1986) and at other surgical meetings in Germany. His concept, however, was ignored. In the middle of the 1980s, the surgical community was still not prepared for the era of “minimally invasive therapy.” Erich Mühe was a surgeon ahead of his time.
The C. elegans nervous system is particularly well suited for optogenetic analyses of circuit function: Essentially all connections have been mapped, and light can be directed at the neuron of interest in the freely moving, transparent animals, while behavior is observed. Thus, different nodes of a neuronal network can be probed for their role in controlling a particular behavior, using different optogenetic tools for photo-activation or –inhibition, which respond to different colors of light. As neurons may act in concert or in opposing ways to affect a behavior, one would further like to excite these neurons concomitantly, yet independent of each other. In addition to the blue-light activated Channelrhodopsin-2 (ChR2), spectrally red-shifted ChR variants have been explored recently. Here, we establish the green-light activated ChR chimera C1V1 (from Chlamydomonas and Volvox ChR1′s) for use in C. elegans. We surveyed a number of red-shifted ChRs, and found that C1V1-ET/ET (E122T; E162T) works most reliable in C. elegans, with 540–580 nm excitation, which leaves ChR2 silent. However, as C1V1-ET/ET is very light sensitive, it still becomes activated when ChR2 is stimulated, even at 400 nm. Thus, we generated a highly efficient blue ChR2, the H134R; T159C double mutant (ChR2-HR/TC). Both proteins can be used in the same animal, in different neurons, to independently control each cell type with light, enabling a further level of complexity in circuit analyses.
Blees, Johanna ; Bokesch, Heidi R. ; Rübsamen, Daniela ; Schulz, Kathrin ; Milke, Larissa ; Bajer, Magdalena M. ; Gustafson, Kirk R. ; Henrich, Curtis J. ; McMahon, James B. ; Colburn, Nancy H. ; Schmid, Tobias ; Brüne, Bernhard
Loss of the tumor suppressor Pdcd4 was reported for various tumor entities and proposed as a prognostic marker in tumorigenesis. We previously characterized decreased Pdcd4 protein stability in response to mitogenic stimuli, which resulted from p70S6K1-dependent protein phosphorylation, β-TrCP1-mediated ubiquitination, and proteasomal destruction. Following high-throughput screening of natural product extract libraries using a luciferase-based reporter assay to monitor phosphorylation-dependent proteasomal degradation of the tumor suppressor Pdcd4, we succeeded in showing that a crude extract from Eriophyllum lanatum stabilized Pdcd4 from TPA-induced degradation. Erioflorin was identified as the active component and inhibited not only degradation of the Pdcd4-luciferase-based reporter but also of endogenous Pdcd4 at low micromolar concentrations. Mechanistically, erioflorin interfered with the interaction between the E3-ubiquitin ligase β-TrCP1 and Pdcd4 in cell culture and in in vitro binding assays, consequently decreasing ubiquitination and degradation of Pdcd4. Interestingly, while erioflorin stabilized additional β-TrCP-targets (such as IκBα and β-catenin), it did not prevent the degradation of targets of other E3-ubiquitin ligases such as p21 (a Skp2-target) and HIF-1α (a pVHL-target), implying selectivity for β-TrCP. Moreover, erioflorin inhibited the tumor-associated activity of known Pdcd4- and IκBα-regulated αtranscription factors, that is, AP-1 and NF-κB, altered cell cycle progression and suppressed proliferation of various cancer cell lines. Our studies succeeded in identifying erioflorin as a novel Pdcd4 stabilizer that inhibits the interaction of Pdcd4 with the E3-ubiquitin ligase β-TrCP1. Inhibition of E3-ligase/target-protein interactions may offer the possibility to target degradation of specific proteins only as compared to general proteasome inhibition.
Wyss, Lena ; Schäfer, Julia ; Liebner, Stefan ; Mittelbronn, Michel Guy André ; Deutsch, Urban ; Enzmann, Gaby ; Adams, Ralf Heinrich ; Aurrand-Lions, Michel ; Plate, Karl ; Imhof, Beat A. ; Engelhardt, Britta
The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C−/− mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C−/− mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C−/− C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C−/− mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3rd ventricle in JAM-C−/− C57BL/6 mice. Taken together, our study suggests that JAM-C−/− C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C.