[Solving the mystery of cellular inclusions. A contribution to the history of virology]. / Das Enträtseln der Zelleinschlüsse. Ein Beitrag zur Geschichte der Virologie.

In the middle of the 19th century cell inclusions were observed with increasing frequency in more and more diseases and were closely scrutinized by researchers working in different fields. Because of their distinct viewpoints, however, the various authors came inevitably to different conclusions. The morphologists interpreted the inclusions as artefacts or degenerative changes, the etiologists, on the other hand, took them for pathogenic protozoa, for cellular lesions inflicted by invisible agents or, conversely--for aggregated products of the cellular defense. Various morphological, parasitological and bacteriological methods have been used to clear up the pros and cons of these hypotheses. It was the rapid progress realized in virology at the middle of the 20th century that finally brought to light their real significance.

[Interpreting cellular inclusions: a contribution to the history of virology]. / Das Entratseln der Zelleinschlusse: ein Beitrag zur Geschichte der Virologie.

In the middle of the 19th century cell inclusions were observed with increasing frequency in more and more diseases and were closely scrutinized by researchers working in different fields. Because of their distinct viewpoints, however, the various authors came inevitably to different conclusions. The morphologists interpreted the inclusions as artefacts or degenerative changes, the etiologists, on the other hand, took them for pathogenic protozoa, for cellular lesions inflicted by invisible agents or, conversely - for aggregated products of the cellular defense. Various morphological, parasitological and bacteriological methods have been used to clear up the pros and cons of these hypotheses. It was the rapid progress realized in virology at the middle of the 20th century that finally brought to light their real significance.

Cytomegalovirus (CMV) in cervical secretion and breast milk. A thirty years perspective.

During the past 30 years prospective epidemiologic studies have clearly established that infants commonly acquire CMV infection in the immediate perinatal or early postnatal period. CMV reaches the offspring with uterine cervical secretions during the birth process and/or with maternal milk during the breast-feeding period, usually resulting in asymptomatic infection in full-term infants. In young women cervical shedding of CMV may reflect a pelvic inflammatory disease and involves the risk of sexual transmission.

[Albert Jesionek tracking cytomegalovirus disease]. / Albert Jesionek auf der Spur der Zytomegaliekrankheit.

The first publications concerning the peculiar cellular structures that later-on became the hallmark of cytomegalic inclusion disease, originated in the early 20th century from German institutes. These early reports got into oblivion even before their significance and implications could be fully realized. The purpose of this study is to reconsider the contributions of Jesionek and other authors to the discovery of the "protozoa-like structures", based upon their publications and in accordance with the state of knowledge at that time.

[Tietze and cytomegalovirus infection of the salivary glands]. / Tietze und die Zytomegalie-Erkrankung der Speicheldrüsen.

Tietze has observed in 1898 the presence of peculiar huge cells in a tumor excised from the parotid gland of an infant. He held the structures for protozoan parasites immigrated from the oral cavity, but they turned out to be cytomegalic inclusion cells. Hence, the first description of cytomegaly-associated symptomatic illness dates back to Tietze's paper. It appears that he was the first author to establish the diagnosis in vivo, and his patient was the first one reported having survived this disease.

[Doctor Anglas' observations on the presence of cytomegalic cells in macerated fetal tissues]. / Les observations du docteur Anglas sur la présence de cellules cytomégaliques dans les tissus foetaux macérés.

Early in this century, Anglas had observed in the renal tubules of a macerated fetus unusual giant structures, which turned out to be cytomegalic inclusion cells. But since he omitted to distinguish them by a suggestive term from previously known giant cells, his observation felt into oblivion. Yet, it constituted the first report on the occurrence of cytomegaly in France, and in general, the first indication of the histogenic origin of these cells, as well as of their resistance to autolysis.

100 years of cytomegalovirus research: an overview.

The early belief that CMV infection is lacking any obvious clinical or pathological feature which would permit its recognition (19) was followed by a centennial effort to delineate the genuine clinical picture of the disease, until it became evident that infections with this virus are resulting in a wide range of syndromes (6) correlated with the age (70) and/or the immune status of the host (75), rather than causing a single morbid entity. Even a given syndrome may yield various manifestations (39). Transition of one CMV-induced syndrome to another (61), and the concomitance of two different clinical aspects at distinct body sites, as well as the concurrent evolution of a localized CMV process and systemic CMV illness in the same host, have also been reported (36). Certain organ syndromes appear to be frequently associated with transplantation e.g. interstitial pneumonitis following allogeneic bone marrow grafting, or with a severely immunocompromised state, e.g. CMV retinis in AIDS patients. Maximal therapeutical immunosuppression appears to exagerate the clinical symptomatology of CMV infection, and in AIDS patients the concomitant CMV disease attains epidemic proportions and a dramatic, constantly fatal course (18). Conversely, intercurrent CMV infections may constitute a terminal lethal complication of AIDS.

Tubular structures occurring in cells infected with herpesviruses.

Certain viruses belonging to the Herpesviridae family generate tubular structures of three distinct size ranges late in the growth cycle. The smallest tubules are about 10 to 20 nm in diameter, and are restricted to the cell nucleus, tending to form palisades of lattice-like structures. The medium sized tubular structures are about the width of a core particle, measuring 55 to 65 nm in diameter, while the larger tubular structures are the same diameter as viral capsids, about 80 to 100 nm. Both are rigid capsomered structures, which are sometimes encountered outside the cell nucleus budding onto spherical particles. The available data on some properties of the various tubular structures, as well as speculations concerning their nature and significance are briefly reviewed. Their importance is emphasized for antigen and vaccine production, as well as in differentiating herpesviruses by electron microscopy.

Particulate structures suggestive of viral infection, visualized in human uterine cervix cancer cells.

Various types of intranuclear particles and intramitochondrial inclusions of possibly viral nature are demonstrated by thin-section electron microscopy of uterine cervix cancer cells, as well as in mast cells infiltrating the tumor stroma, and their significance is briefly discussed.

Phosphonoacetic acid-induced morphological changes of herpesvirus growth in vitro.

Thin-section electron microscopy of Herpesvirus hominis type 1 (HV-1)-infected HEp-2 cells exposed to 100 micrograms/ml phosphonoacetic acid (PAA) revealed not only a spatial restriction of virus multiplication to a few spheroid bodies in the nucleus, but also a delay in viral development, resulting in the formation of unusual HV-1 particle rosettes around the spheroid bodies. HV-1-infected cells were lacking, however, the small tubular structures known to accumulate at increased rates in the presence of PAA, in HV-2-infected cells.

The cytomegalic inclusion cell and disease. II. Social behaviour in vitro.

Upon primary cytomegalovirus infection, previously healthy individuals acutely reject the mass of virus-infected cells, by adequate cellular and humoral defence mechanisms. By contrast, the immunologically immature or compromised host, while still able to neutralize extracellular virus, will tolerate the persistence of the allenated population of cytomegalovirus-converted cells. The micropathology of cytomegalovirus-infected monolayers, however, runs a different course, due to the absence of any immune effector in the in vitro systems. In cultured monolayers of fibroblasts, the infected cells are selected out and aggregate engulfing one another to form giant multinucleated structures.

Polymorphism of nuclear inclusions in carcinoma of the cervix uteri.

Frequency, polymorphism and ultrastructural characteristics of the nuclear inclusion bodies encountered in cancers of the uterine cervix are reported and briefly discussed. The nuclear inclusions are grouped in three distinct types: a) nuclear bodies (comprising type I and II inclusions according to Bouteille et al.'s classification), b) inclusion of cytoplasmic origin, and c) particles of chromatic material. The ultrastructural aspects of the chromatic particles suggest an early structuration of viral chromatin into core material. There appears to be a direct relation between the frequency of chromatic particles and raised antiherpetic antibodies in the patient's sera.