Charles Boyd Kelsey (1850-1917). The pioneer of rectal surgery in USA.

Charles Boyd Kelsey (1850-1917) was a pioneer rectal surgeon. His surgical career was dedicated in the surgery of the rectum, anus, hemorrhoids, and pelvis. He invented also surgical instruments. He managed to be recognized as a pioneer of Rectal surgery not only in America but worldwide. He was a prolific writer and a famous teacher.

Edward Hickling Bradford (1848-1926): The Founder of Pediatric Orthopedics in America.

Edward Hickling Bradford (1848-1926) is considered as 1 of the most important figures in American and world orthopedics during 19th and early 20th century. His teaching ability, his gifted surgical skills and his innovations in orthopedics attracted the interest of the world orthopedic's community and gave him a long lasting reputation. But most of all he is considered as the founder of pediatric orthopedics in America.

Professor Paul Jules Tillaux (1834-1904): His Contribution to Surgery and His Unknown Pioneer Work in Ophthalmic Surgery.

Backround. Professor Paul Jules Tillaux (1834-1904) is considered to be a leading figure in the field of surgery during the 19th century. Methods. Although his work is mostly linked to orthopedic operations, he contributed a lot in ophthalmology and ophthalmic surgery too. Results. In addition, his masterpieces on topographical anatomy and clinical surgery became the gold standard treatises of the era.

Frank Hartley and his Contribution to Surgery.

Although Frank Hartley (1856-1913) was mostly known as the deviser of the method of bisecting the ganglion of the trigeminal nerve within the skull for the relief of facial neuralgia, it should be noted that he had also done very important work in the surgical treatment of goiter which was neglected at his times but later followed by his successors. Furthermore, he also had interest in the surgical treatment of clubfoot and the exstrophy of the bladder.

Professor William Macewen (1848-1924): The Scottish Pioneer of Surgery.

Professor William Macewen (1848-1924) is one of the most important figures in world's surgery during 18th and early 19th century. He managed to provide numerous innovative techniques and instruments in various fields of surgery such as general surgery, orthopedic surgery, neurosurgery, and thoracic surgery. His innovations had a great impact after his time and constituted the fundaments for further surgical developments. He also was a pioneer in clinical photography with the creation of a huge archive. During his surgical career, he received many honors.

Mathieu Jaboulay (1860-1913) and His Innovations in Vascular and General Surgery.

Mathieu Jaboulay (1860-1913) was an inventor in vascular and general surgery. He fabricated many new surgical techniques and instruments such as Jaboulay method for vascular sutures, Jaboulay anastomotic button, and Jaboulay amputation, known also as hemipelvectomy. In addition, he was a pioneer in heterologous transplantation and sympathectomy. He found death suddenly in a terrible train crash. He was a reputable Professor of Surgery at Lyon Faculty of Medicine with prestigious students in vascular surgery.

Philip Henry Mules (1843-1905) and his innovations in ocular surgery.

INTRODUCTION: The aim of the present study is to present an historical overview of the innovations in ocular surgery introduced by the very important surgeon, but mainly unknown, Philip Henry Mules (1843-1905). METHODS: Philip Henry Mules introduced the Mules' evisceration operation and the Mules' ptosis operation. He also invented surgical instruments such as Mules' scoop, Mules' repository, and Mules' enucleation scissors. He was interested also in ocular infection. RESULTS: Many of the innovations in ocular surgery introduced by Philip Henry Mules are still in use. CONCLUSIONS: Philip Henry Mules (1843-1905) was a respectable English ophthalmologist, who despite his short life, only 62-years-old, his innovations in ocular surgery were considered a breakthrough in the late nineteenth century, because in almost every textbook of ophthalmology they were cited and deserved a great merit.

Eugène Louis Doyen (1859-1916): The Reformer of French Surgery.

Eugène Louis Doyen (1859-1916) is considered as the reformer of French surgery at the end of 19th and early 20th century. Although he had a short life, dying at the age of 57, he left his mark in the history of French medicine and especially surgery, not only because he introduced many new medical instruments but also for his innovative idea to introduce cinematography in surgical education, which is crucial until today in the education of every surgeon in the world.

Expression and regulatory effects of murine Schlafen (Slfn) genes in malignant melanoma and renal cell carcinoma.

There is emerging evidence that the IFN-inducible family of Slfn genes and proteins play important roles in cell cycle progression and control of cellular proliferation, but the precise functional roles of different Slfn members in the regulation of tumorigenesis remain unclear. In the present study, we undertook a systematic analysis on the expression and functional relevance of different mouse Slfn genes in malignant melanoma and renal cell carcinoma cells. Our studies demonstrate that several mouse Slfn genes are up-regulated in response to IFN treatment of mouse melanoma and renal cell carcinoma cells, including Slfn1, Slfn2, Slfn4, Slfn5, and Slfn8. Our data show that Slfn2 and Slfn3 play essential roles in the control of mouse malignant melanoma cell proliferation and/or anchorage-independent growth, suggesting key and non-overlapping roles for these genes in the control of malignant melanoma tumorigenesis. In renal cell carcinoma cells, in addition to Slfn2 and Slfn3, Slfn5 also exhibits important antineoplastic effects. Altogether, our findings indicate important functions for distinct mouse Slfn genes in the control of tumorigenesis and provide evidence for differential involvement of distinct members of this gene family in controlling tumorigenesis. They also raise the potential of future therapeutic approaches involving modulation of expression of members of this family of genes in malignant melanoma and renal cell carcinoma.

The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction.

Insulin-like growth factor-1 (IGF-1) isoforms are expressed via alternative splicing. Expression of the minor isoform IGF-1Eb [also known as mechano-growth factor (MGF)] is responsive to cell stress. Since IGF-1 isoforms differ in their E-domain regions, we are interested in determining the biological function of the MGF E-domain. To do so, a synthetic peptide analog was used to gain mechanistic insight into the actions of the E-domain. Treatment of H9c2 cells indicated a rapid cellular uptake mechanism that did not involve IGF-1 receptor activation but resulted in a nuclear localization. Peptide treatment inhibited the intrinsic apoptotic pathway in H9c2 cells subjected to cell stress with sorbitol by preventing the collapse of the mitochondrial membrane potential and inhibition of caspase-3 activation. Therefore, we administered the peptide at the time of myocardial infarction (MI) in mice. At 2 weeks post-MI cardiac function, gene expression and cell death were assayed. A significant decline in both systolic and diastolic function was evident in untreated mice based on PV loop analysis. Delivery of the E-peptide ameliorated the decline in function and resulted in significant preservation of cardiac contractility. Associated with these changes were an inhibition of pathologic hypertrophy and significantly fewer apoptotic nuclei in the viable myocardium of E-peptide-treated mice post-MI. We conclude that administration of the MGF E-domain peptide may provide a means of modulating local tissue IGF-1 autocrine/paracrine actions to preserve cardiac function, prevent cell death, and pathologic remodeling in the heart.

Role of interferon {alpha} (IFN{alpha})-inducible Schlafen-5 in regulation of anchorage-independent growth and invasion of malignant melanoma cells.

IFNα exerts potent inhibitory activities against malignant melanoma cells in vitro and in vivo, but the mechanisms by which it generates its antitumor effects remain unknown. We examined the effects of interferon α (IFNα) on the expression of human members of the Schlafen (SLFN) family of genes, a group of cell cycle regulators that mediate growth-inhibitory responses. Using quantitative RT-real time PCR, we found detectable basal expression of all the different human SLFN genes examined (SLFN5, SLFN11, SLFN12, SLFN13, and SLFN14), in malignant melanoma cells and primary normal human melanocytes, but SLFN5 basal expression was suppressed in all analyzed melanoma cell lines. Treatment of melanoma cells with IFNα resulted in induction of expression of SLFN5 in malignant cells, suggesting a potential involvement of this gene in the antitumor effects of IFNα. Importantly, stable knockdown of SLFN5 in malignant melanoma cells resulted in increased anchorage-independent growth, as evidenced by enhanced colony formation in soft agar assays. Moreover, SLFN5 knockdown also resulted in increased invasion in three-dimensional collagen, suggesting a dual role for SLFN5 in the regulation of invasion and anchorage-independent growth of melanoma cells. Altogether, our findings suggest an important role for the SLFN family of proteins in the generation of the anti-melanoma effects of IFNα and for the first time directly implicate a member of the human SLFN family in the regulation of cell invasion.

Actin is part of pre-initiation complexes and is necessary for transcription by RNA polymerase II.

Actin is abundant in the nucleus and has been implicated in transcription; however, the nature of this involvement has not been established. Here we demonstrate that beta-actin is critically involved in transcription because antibodies directed against beta-actin, but not muscle actin, inhibited transcription in vivo and in vitro. Chromatin immunoprecipitation assays demonstrated the recruitment of actin to the promoter region of the interferon-gamma-inducible MHC2TA gene as well as the interferon-alpha-inducible G1P3 gene. Further investigation revealed that actin and RNA polymerase II co-localize in vivo and also co-purify. We employed an in vitro system with purified nuclear components to demonstrate that antibodies to beta-actin block the initiation of transcription. This assay also demonstrates that beta-actin stimulates transcription by RNA polymerase II. Finally, DNA-binding experiments established the presence of beta-actin in pre-initiation complexes and also showed that the depletion of actin prevented the formation of pre-initiation complexes. Together, these data suggest a fundamental role for actin in the initiation of transcription by RNA polymerase II.

Historical pearls of HPV research: from condyloma to cervical cancer.

The oldest discovered human papilloma virus (HPV) infection in an ancient Egyptian mummy testifies that there is still much to unearth in its history. The Graeco-Roman world recognized venereal infections, and its nomenclature is still valid concerning HPV lesions. Western Europeans, eons later, created various theories for HPV evolution. Animal experiments during the 19th century had a profound impact for the understanding of HPV. In the late 20th century the arcinogenic properties of the virus had been clarified. This historical review presents the most important figures and discoveries in HPV research.

Human Schlafen 5 (SLFN5) Is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma Cells.

We provide evidence that human SLFN5, an interferon (IFN)-inducible member of the Schlafen (SLFN) family of proteins, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expression of the matrix metalloproteinase 1 gene (MMP-1), MMP-13, and several other genes involved in the control of malignant cell motility. Importantly, our data establish that SLFN5 expression correlates with a better overall survival in a large cohort of patients with RCC. The inverse relationship between SLFN5 expression and RCC aggressiveness raises the possibility of developing unique therapeutic approaches in the treatment of RCC, by modulating SLFN5 expression.

The schlafen family of proteins and their regulation by interferons.

The Schlafen (SLFN) family of proteins includes several mouse and human members. There is emerging evidence that members of this family of proteins are involved in important functions, such as the control of cell proliferation, induction of immune responses, and the regulation of viral replication. These proteins span across all species with great diversity, with 10 murine and 5 human isoforms. Recent work has established that mouse and human SLFN proteins are regulated by interferons (IFNs). Several Slfn genes were shown to be induced as classical interferon-stimulated genes, and emerging evidence suggests that these proteins play important roles in the growth inhibitory and antineoplastic effects of IFNs. In the current review, the known properties of mouse and human SLFNs are reviewed, and the implications of their emerging functions are discussed.