A brief history of myelinated nerve fibers: one hundred and fifty years of controversy

The early controversies over myelinated nerve fibers focused on whether nerves are hollow or not, whether the fatty “marrow” (myelin) is inside the nerve fiber or around it, whether myelin is secreted by the axon or formed by another cell, whether nerve fibers are discrete or part of a syncytial network, whether nodes of Ranvier are present in central myelin or only in peripheral myelin. Since Geren's seminal discovery that peripheral myelin is formed by the Schwann cell plasma membrane wrapped around the axon, the focus has shifted. Myelin is clearly a living cell appendage, and the myelin sheath is dependent upon intercellular interactions not only during its formation, but throughout its lifetime and during pathological processes affecting either the axon or the myelin-forming cell. The myelinated fiber is a functional unit, an exquisite symbiosis, whose ability to perform optimally, in some cases whose very survival, depends on the effects the respective cells exert on one another. How are these interactions mediated? Which structures and functions depend on such interaction and which are independent of it? How do cells of the size and shape of myelin-forming cells cope with their metabolic demands and support their most distal components? What are the mechanisms and mutual consequences of demyelination or axonopathy? Relevant studies have burgeoned with the development of molecular biological and genetic engineering methods, and with improvements in microscopy, in vitro culture and specific immunostaining methods. This introductory essay provides an overview of the structural background and continuing controversies relevant to the articles that follow, which represent a sampling of current work and present new information on the molecular structure, function and pathology of myelin and axoglial interactions.

     

The first fifty years of the Connecticut Tumor Registry: reminiscences and prospects

The first fifty years of the Connecticut Tumor Registry (1935-1985) have seen unprecedented progress in the collection of standardized data on cancer patients and in the processing of these data, from paper documents to punch cards and magnetic tapes. The need for collecting such information was first recognized, in the early 1930s, by a group of physicians, health professionals, and laymen in New Haven who observed alarming increases in cancer rates and poor survival of cancer patients in this city. This paper recalls the growth and development of the registry and the role played by the Connecticut legislature, the State Medical Society, the Connecticut Department of Health, and the National Cancer Institute in this process. For half a century, the registry has provided assistance to practitioners, hospitals, and research scientists, not only in Connecticut but across the country and around the world. By making available reliable data on incidence and survival, the registry has played a key role in patient management, clinical trials, and etiologic studies. It has also demonstrated the value and served as an exemplary model of a population-based registry. At this juncture in its history, prospects for the future of the Connecticut Tumor Registry appear bright. Its data base will be an essential resource for the recently established Cancer Control Research Unit (CCRU) in the state and for new intervention studies by investigators at Yale, the University of Connecticut, and the State Health Department.     

Bovine pancreatic ribonuclease: fifty years of the first enzymatic reaction mechanism

Fifty years ago, the group of Tony Mathias and Bob Rabin at University College London deduced the first mechanism for catalysis by an enzyme, ribonuclease [Findlay, D., Herries, D. G., Mathias, A. P., Rabin, B. R., and Ross, C. A. (1961) Nature 190, 781-784]. Here, we celebrate this historic accomplishment by surveying knowledge of enzymology and protein science at that time, facts that led to the formulation of the mechanism, criticisms and alternative mechanisms, data that supported the proposed mechanism, and some of the refinements that have since provided a more precise picture of catalysis of RNA cleavage by ribonucleases. The Mathias and Rabin mechanism has appeared in numerous textbooks, monographs, and reviews and continues to have a profound impact on biochemistry.     

The early years of coeducation at the Yale University School of Medicine.

The Yale School of Medicine began accepting women as candidates for the degree of medicine in the fall of 1916. This decision was consistent with the trend in medical education at the time. While Yale was not the first prestigious Eastern medical school to admit women, joining Johns Hopkins (1893) and the University of Pennsylvania (1914), it was not one of the last. Columbia University College of Physicians and Surgeons admitted women a year later, but Harvard Medical School held out until 1945. The years 1916--1920 saw the number of women enrolled in medical school almost double. Yale''s decision to admit women seems to have been made with little resistance from the faculty. The final decision was made through the encouragement and financial help of Henry Farnam, a professor of economics at Yale, who agreed to pay for the women''s bathrooms. His daughter, Louise, was in the first class of women. At graduation she was awarded the highest scholastic honors, the Campbell Gold Prize. From Yale she travelled to the Yale-sponsored medical school in Changsha, China, where she became the first female faculty member, a position she held for twelve years. The impressions of Ella Clay Wakeman Calhoun, the only woman to graduate in the second class of women, are presented here. Since 1916 the Yale School of Medicine has undergone extensive physical and philosophical changes, developments in which women have participated.     

Perinatal outcome analysis of twin pregnancies at the Department of Obstetrics and Gynecology Central Clinical Hospital of Ministry of Interior and Administration in Warsaw in the years 2005-2006

A group of 59 twin pregnant women who gave birth at the Department of Obstetrics and Gynecology Central Clinical Hospital of Ministry of Interior and Administration in Warsaw in the years 2005-2006. The patients have been divided into four groups: spontaneous twin pregnant women (n=16), twin pregnant women after in- vitro fertilization (IVF) (n=11), twin pregnant women after in-vitro fertilization with intracytoplasmic sperm injection (ICSI) (n=29) and twin pregnant women after ICSI and transfer of frozen embryos (n=3). In one case intrauterine death of one of twins in the 34th week of gestation has been noticed. The cause of the death was umbilical cord wrapped around his neck. The gestation was ended with cesarean section and Apgar score of the second twin was 8 in the fifth minute. In one case there was an urgent indication for a cesarean delivery of children with a very low birth weight (because of intrauterine infection, preterm labor in progress) and in three cases at least one of twins with a low birth weight. Among the group 19 women (32%) have given birth prematurely. The Apgar score in the first, third and fifth minute has been statistically significant and inversely proportional dependent only on the gestational age. There were no differences in birth weight among study groups regardless the way of conception. Only two spontaneous twin pregnant patients have had a vaginal labor. By the remaining 57 patients there has been an elective cesarean section in thirty five cases and there has been an urgent indication for cesarean section in twenty two cases.     

Marine Lake Mogilnoe (Kildin Island,the Barents Sea): one hundred years of solitude

Lake Mogilnoe (Kildin Island, the Barents Sea) is a marine stratified lake, a refuge for landlocked populations of marine organisms. Unlike other known marine lakes from polar areas, which communicate with the sea by water percolation at the surface, Mogilnoe has a subterranean connection with the sea like tropical and subtropical anchialine lakes. Similarly to some other marine lakes, Mogilnoe has traditionally been considered to be biologically isolated from the sea and subject to little change. We review the current status of the physical features, zooplankton and benthos of Mogilnoe and trace changes that have occurred in the lake since the start of observations in 1894. The anaerobic bottom water layer has expanded by 100 %, while the upper freshwater layer has diminished by 40 %. The species diversity of zooplankton and macrobenthos has halved. The occurrence of Atlantic cod likens Mogilnoe to some other Arctic marine lakes while the presence of large flocks of sea anemones, scyphomedusae and suberitid sponges makes it similar to tropical anchialine lakes. Lake Mogilnoe is not entirely biologically isolated; accidental introduction of species from the sea does occur. We argue that the idealised model of an isolated steady-state ecosystem can be applied to a marine lake with caution. A model of fluctuating abiotic environment and partial biological isolation portrays the real situation better.     

The Yale Plan of Medical Education: the early years

This paper considers the early years of the Yale Plan of Medical Education, which has come to be called the Yale System. It chronicles and analyzes the incremental development of the System and considers evaluations of the plan and modifications introduced over time. Also considered are external factors which influenced design and implementation. The paper covers the period of medical education at Yale from the 1920s to the early 1950s.     

Ovarian carcinoma of low malignant potential treated at the 1(st) Department of Obstetrics and Gynecology Semmelweis University Faculty of Medicine,between 1990 and 2000

The authors analyzed the epidemiologic and histological characteristics and the management of ovarian carcinoma of low malignant potential (LMP) at a university hospital between 1990 and 2000. The authors carried out a retrospective study reviewing hospital charts. Based on the records experience with 29 such tumors is peresented. Of these 20 (74%) were of the serous variety, 7 (26%) were mucinous. LMP tumors accounted for 16% of proliferating epithelial ovarian tumors. They occured at a mean age of 45 years. The LMP tumors were bilateral in 12% of the cases. The majority of patients (87%) with LMP tumors presented with early stage disease. Tumor markers such as CA-125 were not always elevated as in invasive ovarian carcinoma. Laboratory investigations have not demonstrated that these tumors represent an intermediate step between benign ovarian tumors and carcinoma. The recommended therapy is surgical, consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and tumor debulking. Conservative surgery consisting of unilateral salpingo-oophorectomy is considered to be an appropriate treatment for young women with early stage LMP ovarian tumors who wish to retain their fertility potential. 50 percent of women who underwent conservative surgery subsequently conceived in this study. There were no recurrences in the study group, so the authors conclude that the long term outcome of LMP tumors is extremely favorable.     

C.-E.A. Winslow and the later years of public health at Yale, 1940-1945

This paper is one of a series of papers in which I consider contemporary Yale medical education in general and the Yale Department of Epidemiology and Public Health in particular. It tells of the retirement in 1945 of C.-E.A. Winslow, Professor and Chairman of the Yale Department of Public Health since its inception in 1915; of the committees established by the dean of the School of Medicine and the president of the University, charged with determining the future direction of the department; and of the outcome, which, in 1945, proved favorable to Winslow's public health philosophy in contrast to the medical school's clinical needs and desires.     

Epilogue – one hundred years of nemertean research: Bürger (1895) to the present

The past one hundred years of research on nemerteansis reviewed. Scientific methodology and philosophyhave advanced considerably during this period, yetnemerteans remain one of the least well known ofinvertebrate groups; nemerteans are not just membersof a minor phylum, they constitute a neglected yethighly successful assemblage of animals. Despite manyworkers in the last hundred years having madesignificant contributions to our knowledge about thisphylum of worms, many aspects of their biology arestill virtually, if not totally, unknown, and theenormous advances in many areas of scientificknowledge have not been paralleled by comparable gainsin our understanding of nemerteans.