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Biomedical subjects

M Wolman

Publications and source records attributed to M Wolman.

At least 73 records · Page 4Linked to original sources

The role of macrophages and polymorphs in the levan-induced inhibition of Lewis lung carcinoma in C57BL mice.

High-mol.-wt levan injected locally inhibits the growth of Lewis lung carcinoma in C57BL mice. The inhibition is dependent on the number of tumour cells injected and on the dose of levan. The inhibition decreases tumour incidence and size as well as prolonging survival. The polysaccharide is most effective when injected daily beginning on the day of tumour-cell inoculation. Treatment begun on later dates is less effective. Treatment begun one day before tumour-cell inoculation enhances tumour growth. Histological studies showed that levan induces an intense polymorphonuclear (PMN) reaction followed by accumulation of vacuolated, levan-laden macrophages. Both PMN and activated macrophages seemed to have an inhibitory effect upon the growth of the tumour. The effector role of PMN was not explained by the histological study. Tumour cells in close contact with levan-laden macrophages appeared mostly necrotic. Administration of levan begun one day before tumour-cell inoculation produced a similar reaction, but the infiltrating cells did not appear to approach and damage the tumour cells.

Animals↗

Kawasaki's disease and infantile polyarteritis nodosa: is Pseudomonas infection responsible? Report of a case.

A nineteen-month-old child presented with a febrile illness, skin rash, painful swelling of the joints, lymphadenopathy and hepatosplenomegaly. Pseudomonas was cultured from the blood during life and, subsequently, at autopsy. Autopsy revealed a generalized panarteritis involving the coronary, retroperitoneal and pulmonary arteries with thickening of arterial walls and narrowing of the lumina. Thrombi and foci of necrosis and infarcts were found in many organs. Numerous bacilli were present in fresh lesions, but not in the organizing lesions. Periodic acid-Schiff-positive deposits were found in occasional macrophages, in walls of affected vessels, in the marginal sinuses of lymph nodes and diffusely in epicardial and retroperitoneal adipose tissue. The findings suggest that some or even all cases of Kawasaki's disease and infantile polyarteritis nodosa may be caused by Pseudomonas sepsis. It is also suggested that the vasculitis and paucity of inflammatory reaction in many cases of Pseudomonas sepsis might be related to the fact that many strains of Pseudomonas produce high-molecular-weight levan (or another polysaccharide). This compound is known to inhibit the inflammatory reaction and to increase bacterial pathogenicity.

Arteries↗

Mineralized cells: neurons, glia or macrophages? Ultrastructure of cerebellum in chick nutritional encephalopathy.

Mineralized dead cells were found in infarcted areas in the cerebella of three chicks killed in the healing stage of nutritional encephalopathy. The mineral depostis were found in vacuoles and consisted of radially packed threads and spicules, concentric laminated structures and centrally located amorphous masses. The cells in which these deposits were found were positively identified as astrocytes and macrophages. The presence of such deposits in neurons was suspected but not proven.

Animals↗

The inhibitory effects of high molecular levan on transport across the vascular wall stimulated by histamine.

Administration of levan to mice and rats inhibited the passage of intravenously injected trypan blue into the area of skin injected with histamine. In the mouse, the optimal dose of levan was about 5 mg/25 g body weight; higher doses, on the other hand, enhanced diffusion. In the rat, the inhibitory effect was directly related to the dose of levan, the optimal dose being five times higher than for mice. Treatment of rats with levan caused a marked reduction in the uptake and transport of colloidal carbon. In normal and histamine- or turpentine-injected cremaster muscles, treatment with levan prevented carbon from being adsorbed and endocytosed by the endothelial cells. Levan itself was frequently attached to the lumenal surface of endothelial cells, or less frequently was enclosed within pinocytic vesicles. Occasionally, transport across the interendothelial junction was also seen, but the impression gained was that the frequency and extent of patent junctions were reduced in animals receiving phlogistic stimuli and treated with levan. Carbon particles were generally aggregated in the central zone of vessels and were seldom seen near the endothelial cells, within endothelial cells or within any open junctions, presumably because of the coating effect of levan. With partly depolymerised levan, carbon particles were found in endothelial cells and intercellular spaces, but at lower concentrations than in non-levanised control animals. It is suggested that levan acts by altering the rheologic patterns in the microcirculation, by modifying the surface of endothelial cells and by influencing their behaviour, and, finally, by changing the constitution of the ground substance and basement lamina.

Animals↗

Histological study of homografts showing delayed rejection following levan administration.

The delaying effect of continued administration of levan on mouse skin homograft rejection was found to be due mainly to inhibition of thrombotic occlusion of the nutrient blood vessels. Levan administration did not appear to affect epidermal regeneration, but it seemed to inhibit degranulation of mast cells, resorption of plasma extravasated during the operation and growth of granulation tissue. The delayed rejection caused by levan treatment was apparently caused by infiltration of the graft by activated mononuclear cells from the blood stream. The phenomenon is believed to represent a late stage of the graft rejection process, its apperance depending on the survival of the graft beyond the stage of vascular occlusion.

Animals↗

The tissue reaction to implanted foreign bodies in levan-treated mice.

The effect of local administration of levan on the reaction to foreign bodies was studied in the subcutaneous tissues of mice implanted with sterile cotton wool pellets or Melenex plastic coverslips. Treatment with levan reduced leucocytic invasion of the implanted pellets as well as the vasoproliferative response of the surrounding tissue. Reduction in the thickness of the capsule surrounding the implant in levan-treated mice provided further evidence for the latter. Assessment of cells attached onto implanted coverslips showed that levan treatment diminished the number of macrophages attaching to the plastic and significantly reduced the number of nuclei within the multinucleate giant cells formed at the site of implantation. This reduction indicates that levan also exerts an inhibitory action on fusion between macrophages.

Animals↗

Modification of the tuberculin reaction by levan.

High molecular levan (polyfructoside) inhibits the skin tuberculin reaction in guinea pigs as judged by the degree of induration and erythema. The effect is dose-dependent. No effect on cellular infiltration was observed in histological studies. The lymph nodes of levan-treated animals were smaller and exhibited a much milder granulomatous reaction than those of non-treated animals.

Animals↗

The role of acid esterase in the pathogenesis of xanthoma. A histochemical study in rabbits.

Previous studies of our group indicated that two types of cells are involved in the pathogenesis of atheroma. The one type, myocytes, are poor in acid esterase activity, store lipid droplets which they cannot hydrolyze and are transformed into foam cells. The other type, macrophages, are rich in this enzyme activity, can and do hydrolyze the esters with possible healing by fibrosis. In the present study the importance of acid esterase activity in experimental xanthoma in hyperlipidemic rabbits was studied. Perithelial cells of small blood vessels were found to be poor in acid esterase activity and to contain bulky lipid masses. With time, increasing numbers of cells with high enzyme activity were found mainly at a distance from the vessels. These cells, which mostly contained finely emulsified lipids are believed to be macrophages. Thus, in both atheroma and xanthoma, vessel wall cells take a "passive" part in formation of the lesion, while blood borne cells play a role in disposing of the lipid with eventual possibility of healing.

Animals↗

Lipid pigment formation in cultures of chick hepatocytes. Effects of aging and of oxidizable agents.

Tissue cultures of hepatocytes were studied for the formation of lipid pigments as related to aging of the cultures and of the addition to them of: 1) colloidal iron; 2) L-ascorbic acid; and 3) tyrosine. The presence of lipid pigments was gauged by their sudanophilia after a light solvent extraction and yellow autofluorescence. It has been found that all the three agents enhanced pigmentogenesis. It has been concluded that both pro-oxidants and antioxidants may enhance lipid pigment formation: the first by enhancing lipid oxidation, the second by enhancing copolymerization which terminates the oxidative chain.

Aging↗

Histological criteria for immunological rejection of mouse skin homografts.

The sequence of events in homograft rejection of skin in mice was studied by light microscopy in comparison to the reactions to isografts. Male C3H mice were used as donors and Balb/c mice were the recipients. In non-infected grafts no invasion of graft tissue by inflammatory cells occurred except for the marginal areas bordering on the graft bed. The most constant feature of immunological rejection was occlusion of blood vessels at the graft-host border with ischaemia of the graft. This indicated that skin homograft rejection is mainly a vascular phenomenon which can be best diagnosed by the presence of empty venules and capillaries. Leukocytic infiltration was prominent in presumably infected grafts. Destruction and inflammatory infiltration of the epidermis was not found to be a criterion for immunological rejection. In the graft bed adjoining the graft the granulation tissue contained basophilic and small lymphocytes, and macrophages. These cell tended to concentrate nearest to the graft and were surrounded on the outside by the lymphoid cells. It is probable that the macrophages were active in digestion of breakdown products.

Animals↗

The role of smooth muscle cells and hematogenous macrophages in atheroma.

Two types of lipid-containing cells were found in diet-induced atheromata of rabbits. The cells of the first type contained little acid esterase activity, were situated mainly in the deep and middle layers of the intima and constituted the overwhelming majority of foam cells. The lipid contained in them was bulky, indicating inefficient lipid emulsification and metabolism. The cells of the second type were rich in acid esterase activity and were situated in the superficial layer of the intima, often in subendothelial rows. These cells contained lipid which was finely emulsified and present in much smaller amounts than the lipid present in the first type of cell. The localisation of the two types of cells, the observation that only the second type of cell exhibited marked AS-D acetate esterase activity and the study of Adams and Bayliss (1976) indicate that, while the cells of the first type are myogenous, the cells of the second type are hematogenous macrophages. It is proposed that relative insufficiency of acid esterase activity in the myocytes is an important factor in the formation of atheroma. The intense acid esterase activity in the macrophages may play a major role in the healing of atheroma and its transformation into a fibrous plaque.

Animals↗

Tumors and amyloidosis in mice painted with crude oil found on bathing beaches.

Oil lumps collected on the beaches of Israel in 1970, 1971 and 1973 were extracted with pure acetone and the extracts were used to paint the skin of mice twice weekly for 12 months. The oil lumps originated from crude oil spilled from tankers. The less recently collected oils induced papillomata and lymphomata in some animals. They were also more active than the recent oil in the induction of generalized amyloidosis. Mice painted for 12 months with acetone alone developed amyloidosis to a similar extent as those painted with the oldest oil. In previously reported experiments, however, acetone was much less active than the oil in producing amyloidosis after 5 months of painting. The possibility that acetone and oil might act both synergistically or to be antagonistic at different phases of amyloidogenesis is discussed.

Amyloidosis↗

Effects of prolonged administration of high molecular levan on arterial blood gases, oxygen transport and acid base balance in rabbits.

The effect of daily intraperitoneal injections of 100 mg of high molecular levan for 4-6 weeks on a number of physiological parameters was studied in rabbits. The parameters studied included whole blood pH, blood gases and acid-base balance. Control rabbits were similarly treated with physiological saline. In five rabbits T-50 was determined after levan treatment. None of the studied parameters was significantly affected by the levan treatment.

Acid-Base Equilibrium↗

Effects of prolonged administration of high molecular levan on hematological parameters in rabbits.

Rabbits were injected intraperitoneally with 100 mg of high molecular levan, daily for 4--6 weeks. Study of various hematological parameters revealed that the treatment resulted in the following changes: 1. Marked elevation in fibrinogen levels and in the number of platelets. 2. Insignificant changes in the intrinsic and extrinsic clotting mechanisms and in platelet aggregation. 3. Some reduction in the number of circulating RBCs. The findings indicate that levan treatment has no obvious effect on hematologic functions, except for the increase in fibrinogen and platelets and the slight decrease in circulating RBCs.

Animals↗