Thesis--Universität Erlangen-Nürnberg. / At head of title: Aus dem Seminar für Geschichte der Medizin der Universität Erlangen-Nürnberg. Vita.

Gram-negative sepsis is an important cause of the acute respiratory distress syndrome (ARDS). Pulmonary hypertension (PH), which often develops in ARDS, results in part from the remodelling of the pulmonary microvasculature. Vascular pericytes (PC), dedifferentiated smooth muscle-like cells, are thought to playa role in the remodelling and neomuscularization of pulmonary microvessels. Endotoxin, lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria, activates macrophages, endothelial cells, and other cells to release potent cytokine and phospholipid mediators such as plateletactivating factor (PAF). The effects of these mediators on inflammation, vascular permeabilization, and progression of injury have been previously described. However, the role of these mediators in stimulating PC growth during the remodelling process is unknown. We show that compared with control growth, PAF (lO-gM, semisynthetic) stimulates the 7-day mean grovvth of proliferating PC by 31% in medium with serum, and 29% without serum. Furthermore, PAF stimulates the growth of quiescent PC by 12% with serum and 23% without serum. These proliferative effects are blocked by the addition of the PAF-receptor antagonist CV-3988 (lO-7M). The addition of the individual cytokines does not affect PC proliferation in vitro. A mixture of these cytokines, simulating in vivo conditions, does not alter PC proliferation in the iii presence of serum, but reduces it in its absence. LPS from E.coli increases proliferation by 72%, compared with control. The proliferative effect of endotoxin requires the presence of serum. Thus, LPS and PAF, but not inflammatory cytokines. are direct mitogens of lung pericytes in vitro. This is the first demonstration that these molecules have direct effects on cells found in substantial areas of the vessel wall, possibly contributing to the neomuscularization and vascular remodelling of the pulmonary wasculature in acute lung injury. / La septicémie à bactéries gram-négatives est une cause importante du syndrome de détresse respiratoire de l’adulte (SDRA). L’hypertension pulmonaire, qui se développe souvent durant le SDRA, se manifeste en partie par des modifications des micro-vaisseaux pulmonaires. Les péricytes (PC), qui sont des cellules précurseures des muscles lisses, sont impliqués dans la reconfiguration et la néovascularisation des micro-vaisseaux pulmonaires. L’endotoxine, qui est une lipopolysaccharide (LPS) provenant de la membrane extérieure des bactéries gram-négatives, peut activer les cellules macrophagiques, endothéliales, et d’autres cellules de façon à libérer des médiateurs puissants, comprenant aussi les cytokines et le facteur activateur des plaquettes (FAP). Les effets de ces médiateurs sur l’inflammation, la perméabilité vasculaire, et la progression du dommage furent déjà décrits. Mais le rôle de ces médiateurs en stimulant la prolifération des PC durant le processus de la modification vasculaire est inconnu. Nous démontrons que, par rapport au contrôle, FAP (10-9M, semi-synthétique) stimule la croissance moyenne au septième jour des PC “proliférants” de 31% et 29% respectivement avec et sans sérum. En plus, PAF stimule la croissance des PC “dormants” par 12% et 23% respectivement avec et sans sérum. Ces effets prolifératifs sont bloqués en ajoutant l’antagoniste du récepteur de PAF CV-3988 (10-7M). L’addition subséquente et séquentielle des cytokines n’affecte pas la croissance des PC in vitro. Ajoutées simultanement pour reproduire les conditions in vivo, l’addition des cytokines n’affecte pas la croissance des PC en présence de sérum, mais la réduit en son absence. LPS provenant de E.coli augmente de 72% la prolifération par rapport au contrôle. Les effets prolifératifs de l’endotoxine exigent la présence de sérum. LPS et FAP, mais pas les cytokines, peuvent jouer un rôle direct sur les PC$

Early in 1961 it was brought to my attention that rabbits on a cholesterol diet were said to become anaemic. It was suggested that I perform haemograms on some cholesterol-fed and some normal animals to determine if the anaemia actually occurred. The results of this pilot experiment, recorded in the appendix, showed a significant degree of anaemia in six cholesterol- and fat-fed rabbits as compared with normal blood values in ten rabbits on a diet of unadulterated commercial chow. The animals on the atherogenic diet also showed leucocytesis and a quite marked reticulocytosis. The findings prompted a review of the literature on blood changes associated with atherogenic diets, and related regimes.

The existence of fungi capable of capturing and consuming microscopic animals has been known for approximately eighty years; however, it is only during the past three decades that this interesting group of fungi has received the critical attention of an increasing number of workers who are studying them from several aspects. During this period, which was inaugurated by Drechsler in the U.S.A., the range of morphological diversity of these fungi has received considerable attention; some work has been done on their distribution and degree of occurrence in various habitats; aspects of their biology have been studied and attempts have been made to utilize these fungi in the biological control of plant and animal diseases, caused by nematodes, or eelworms as they are sometimes called.

The earliest description of cancer has been traced back to records on Egyptian papyri of the fifteenth century B.C. Following this, in the era of Hippocrates, in the fourth century B. C., the nature of cancer was described as the presence of a tumour, and the absence of any tendency towards healing. Hippocrates used the term “kapkivos” , "carcinos”, for all indolent ulcers, and “kapkivwua”, "carcinoma” for progressive malignant tumours. In spite of many descriptions, and many personal views as to the origin of cancer in the following centuries, little came but mere speculation. Perhaps, the one of the most notable events in the history of cancer research was the essay by Bernard Peyrihle (1735-1804) of Lyon, “Qu’est ce que le cancer?”.

There is evidence that humans have been afflicted with arteriosclerotic vascular diseases for more than 4000 years. Shattock (1908-1909), for example, recorded finding arteriosclerotic changes in an aortic segment removed from the mummy of King Menephtah, allegedly the pharaoh of the Hebrew Exodus. Ruffer (1911) also described arteriosclerotic lesions in the aortae and peripheral arteries taken from a group of mummies thought buried during a 2000-year period ending in 500 B.C. The majority of the lesions in the peripheral arteries of the mummies were undoubtedly of the type now known to be due to Mönckeberg’s sclerosis. Others, particularly those in the aortae, were of a different nature.

Before 1890, theories as to the nature of basement membranes were largely speculations based on descriptive grounds (1,2). Mall appears to have been the first to study basement membranes with techniques specifically designed to elucidate their nature. His researches, in which he used techniques which were very sophisticated for the time, were communicated to the Royal Society of Saxony in 1890 and were published in 1896 (3). [...]

Though resemblance between lesions induced experimentallY in animals and those characterizing diseases in man is no warrant of a common aetiology and pathogenesis, there is a distinct probability that there are certain aetiologic and pathogenetic factors in common. [...]

The clinician knows so well the gripping, cleaving, tightening pain in the chest that bespeaks of narrowing or occlusion of a coronary artery. He has seen the picture often. Half a century ago he called it acute indigestion. [...]

The study of atherosclerosis has been pursued by men in many parts of the world with Churchillian tenacity. The literature published on the facts, and theories about this disease, can only be described as colossal. [...]