Joseph M. Harb

The effect of ingestion of ethyl alcohol, wine and beer on the myocardium of mice.

Abstract Histologic and ultrastructural changes in the myocardium of mice consuming various concentrations of pure ethanol, beer and wine as their sole liquid intake for 4 to 10 weeks are described. Ultrastructural alterations were seen in the sarcoplasmic reticulum, myofilaments and intercalated discs. The changes were minor but discernible. The pathogenesis of these changes is discussed in terms of a possible direct toxic effect of alcohol on the myocardium.

Pathologic changes of aorta and coronary arteries of mice infected with Coxsackie B4 virus.

Summary Coxsackie virus B4 has been shown to produce significant lesions in the large and small blood vessels of 2-day-old and 12-day-old mice. The Coxsackie virus B4-infected mice developed focal endothelial cell degeneration and necrosis with subsequent desquamation and denudation of intima of the aorta, coronary arteries, large veins, and other blood vessels. Viral infections in man are common, but infection of the great blood vessels remains little studied. Viral lesions are suggested as an initiating factor in the production of vascular diseases in man, possibly including atherosclerosis.

Viral infection of the aorta of man associated with early atherosclerotic changes

Abstract A 19-year-old young man who died of viral cardiomyopathy had positive staining of the myocardium, kidney, pancreas, and aorta with immunofluorescent antibodies for Coxsackie B 4 virus. The aorta was found to have an accumulation of lipid material in cells of the intima. The lipid deposits were located electron microscopically in fibroblasts, smooth muscle cells, and macrophages. It is suggested that viral infections, so common in man, may produce local sites of arterial injury which later result in the scars and lipid, calcium, and other deposits which represent the well-known lesions of atherosclerosis and arteriosclerosis. These scars and late lesions must have a beginning, and from the manifestations of immunofluorescent antibodies, histopathologic, and electron microscopic findings in the aorta of the patient described here, as well as from the clinical data, it is suggested that Coxsackie B 4 virus may initiate atherosclerosis and arteriosclerosis in man.

Fine structure of the pseudobranch of the flounder Paralichthys lethostigma

SummaryThe free or “non-glandular” pseudobranch of the flounder Paralichthys lethostigma was studied with the electron microscope. Cells typical of glandular type pseudobranchs are found. This indicates that, at least in the flounder, the free pseudobranch should be called “glandular”. In addition, the chloride-type cells, commonly found in the gill, buccal epithelium, and surface epithelium of other fish, have been found in the pseudobranch, where they have not been described previously. The fine structure of both the chloride-type and the pseudobranch-type cell has been characterized and contrasted. We have not been able to confirm previous reports that the specific cells in both pseudobranch and gill are identical in the flounder.

Fine Structure of Digital Vascular Lesions in Raynaud's Phenomenon and Disease

The ultrastructural changes in the vessels of the fingertips of patients with Raynauds phenomenon or disease, with or without scleroderma, are described for the first time. Fingertip specimens were taken by punch biopsy. The light microscopic changes, including segmental vasculitis, fibrinoid degeneration of capillaries, and involuntary regression of glomus bodies explain the reduced digital blood flow associated with Raynauds disease and phenomenon. The moment-to-moment digital blood flow, recorded rheoplethysmographically, was low when the patient was in a comfortable environment and was increased in a hot environment. This result substantiates the therapeutic importance of reflex vasodilatation. These findings correlate well with the ultrastructural changes in capillaries, including multiple cytoplasmic folds in endothelial cells, abundant intracytoplasmic filaments, and unusual incorporation of collagen fibrils in the basement membrane. These changes must influence nutritional and thermoregulatory function of the digital blood vessels.

Mural and valvular endocarditis of mice infected with encephalomyocarditis (EMC) virus

Abstract The encephalomyocarditis (EMC) virus is shown to infect readily the heart of mice and to produce myocarditis and valvular endocarditis. In these experiments 1–2 day old newborn mice were found to have extensive mural and valvular endocardial damage, whereas the adult mice had only minor lesions. The pathologic changes include degeneration and necrosis of lining endothelial and stromal cells and inflammatory changes of the valves. The finding of EMC viral crystals in the valves and myocardium of these animals proves the direct entry of virus into the valvular tissue and muscles of the heart. EMC virus can cause both mural and valvular endocarditis in newborn mice. These experiments, with the fact that the EMC virus forms readily detectable crystals, establish a good model for studying viral endocarditis and the natural history of the disease in animals and lend further support to the probable role of viruses in the production of valvulitis in man.

Encephalomyocarditis (EMC) virus infection of the mouse aorta. An ultrastructural study.

Abstract Electron microscopic findings in the aortas of 10 mice infected with encephalomyocarditis (EMC) virus are described. Cellular necrosis was found mostly in the adventitia and occasionally in the smooth muscle cells closest to the adventitial tunic. Viral crystals were frequently found in association with the intracellular necrosis. Viral crystals were found in the adventitia of all 10 mice and in the smooth muscle cells of the media in some of the animals. The relationship of these findings to the production of aortitis or arteritis, which could also ultimately result in arteriosclerosis, is discussed.

Pancreatic islet cell damage in mice produced by coxsackie B 1 and encephalomyocarditis viruses.

In den β-Zellen der Langerhansschen Inseln des Pankreas wurden Viruskristalle von mit Encephalomyocarditis-Virus oder Coxsackie-B10Virus infizierten Mäusen gefunden. Die Inselzellen zeigten sowohl leichte als auch schwere Schädigung.

Electron microscopic studies of viral pancreatitis in Coxsackie B4 virus infected mice

Abstract Using a high titer culture of Coxsackie B 4 virus, cytonecrosis consistent with picornaviral infection and cytopathic changes indicative of viral pancreatitis were produced in the pancreas of newborn mice. Virocytonecrosis was manifested within acinocytes by formation of characteristic membrane-vesicle complexes, dilatation of rough endoplasmic reticulum, margination of nuclear chromatin, pyknosis of nuclei, and acute inflammation. Viral pancreatitis was characterized by formation of cytosegresomes, fibroid bodies, and sloughed damaged acinar cytoplasm apparent in autophagic vacuoles of macrophages. Immature leucocytic cells were closely aligned to the wall of acinar ducts. Beta cell damage was also observed. Of significance was the observation of aggregates of Coxsackie B 4 virus particles in various pancreatic cells of 11 of the 23 mice studied. These aggregates appeared in the typical crystalline form with cubic and hexagonal lattice configurations and as viral particles circularly arranged into eight-sided and ten-sided “rosettes.” These findings strongly support the concept that viruses are etiologic agents in pancreatitis and diabetes mellitus.

Coxsackie B4 Virus Crystal Formation in Mouse Pancreas

Summary For the first time, Coxsackie B4 virus crystals are demonstrated in tissues of animals inoculated with the virus. Until this report, Coxsackie B4 virus had never been found to form crystalline aggregates in tissues of any kind. The viral crystals which were located in the pancreas of newborn mice were associated with ultrastructural damage to the pancreas not observed in control animals, thereby indicating that viruses directly invade and damage these tissues. Thus, this virus must be considered among etiologic factors in pancreatic disease.