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Biomedical subjects

M Wolman

Publications and source records attributed to M Wolman.

At least 55 records · Page 3Linked to original sources
PubMed1983

Effects of chlorocyclizine on pulmonary lipid metabolism in rats.

Pulmonary lipidosis was induced in rats by including 0.36 and 0.54% chlorocyclizine in their diet. Chemical analyses of the lung tissue revealed a very marked increase in phosphatidylcholine concentration. Phosphatidylglycerol and phosphatidylinositol concentrations were also markedly increased. An increase in the phosphatidylcholine content was also observed in lavage fluid and macrophages. Microscopic examination of the cell fraction showed that almost all the cells of the lavage fluid were macrophages and that histochemically demonstrable acid esterase activity was mostly inversely related to storage of lipids in the cells. Sonication of macrophages isolated from normal or chlorocyclizine-treated rats yielded a soluble acid phospholipase (pH optimum, 4.0) and a neutral (pH optimum, 8.2) membrane-bound, CaCl2-dependent enzyme. An inhibitory effect of chlorocyclizine in vitro on the activity of the soluble phospholipase was shown.

Animals↗
PubMed1983

Effect of administration schedule on the levan-cyclophosphamide combined treatment of Lewis lung carcinoma.

Combined treatment with levan and cyclophosphamide (CY) was applied intratumorally to Lewis lung carcinoma tumors in C57B1 mice on day 5 after tumor cell inoculation. Although on that day levan alone had no effect and CY alone caused only temporary regression of tumors, the combined CY-levan treatment caused 60% cure. Levan given before CY was almost as effective as simultaneous administration of both drugs on day 5. Delaying the administration of levan after CY treatment reduced the therapeutic effect. It is concluded that timing in relation to tumor cell inoculation as well as the order of administration of drugs, determine the degree of therapeutic efficacy. In tumor chemo-immunotherapy the final effect is probably due not only to the anti-tumoral effect per se of each drug, but also to the fact that the two agents have an effect on the immune system. Since the immune response may change during tumor development, the effect of timing of administration of an immunomodulator and certainly to two immunomodulators, can be crucial.

Animals↗
PubMed1983

Combined effect of levan and cytotoxic agents on the growth of experimental tumours in mice.

The combined effect of the polysaccharide levan (previously shown to exert a host-dependent as well as direct antitumoural activity) and the cytotoxic agents cyclophosphamide (CY), methotrexate (MTX), vincristine (VINC) and 5-fluoro-uracil (SFU) was studied in Lewis lung carcinoma and AKR lymphoma. Combined chemo- and immunotherapy was applied beginning on the day of tumour cell inoculation. Additive effects were obtained with the combined treatments, compared to single treatments, with all the combinations except MTX-levan in Lewis lung carcinoma, where the combined effect was synergistic. The additive effect was obtained with different doses and routes of chemotherapy, whether local or intraperitoneal. A 2 mg dose of CY combined with levan administered at daily doses of 10 mg, resulted in a 100% prevention of Lewis lung carcinoma growth. It is suggested that the levan may have two beneficial effects: it can exert an inhibitory effect on tumour growth and diminish the deleterious effect of cytotoxic agents on the immune system.

Animals↗
PubMed1981

Evaluation of the dye-protein tracers in pathophysiology of the blood-brain barrier.

1. Sodium fluorescein and Evans Blue, commonly used tracers in the study of blood-brain barrier disturbances, revealed considerable differences in their respective protein binding capacity in the plasma, passage through the barrier and in the rate of their elimination from the brain parenchyma. 2. In the plasma a considerable portion of the sodium fluorescein remains free and behaves like a micromolecular barrier tracer. On the other hand, almost complete binding of the Evans Blue to albumin confers to it properties of a protein tracer. 3. Following the extravasation of the tracers, the sodium fluorescein is relatively soon eliminated, whereas Evans Blue remains in the cellular elements of the brain parenchyma for a considerable time, although the protein moiety of the tracer is removed much sooner from the cytoplasm of glial cells, presumably by the lysosomal digestion.

Animals↗
PubMed1981

Differentiation of macrophages from Lewis lung carcinoma tumour cells in tissue sections by their alpha-naphthyl butyrate esterase activity.

The activities of alpha-naphthyl butyrate esterase, non-specific esterase, indoxyl esterase and acid phosphatase were studied histochemically in macrophages in cultures and in tissue sections of primary tumours and metastases of Lewis lung carcinoma (3LL). All macrophages in culture were stained by the alpha-naphthyl butyrate esterase procedure. In tissue sections, macrophages were intensely stained by the butyrate esterase procedure, while the tumour cells were not stained at all; macrophages were easily differentiated from 3LL cells. Non-specific esterase was evident in both tumour cells and macrophages. Indoxyl esterase and acid phosphatase were present in macrophages at the margin of the tumour only. The alpha-naphthyl butyrate esterase-positive macrophages differed in shape and location from acid phosphatase and indoxyl esterase-positive macrophages. This may indicate a difference in characteristics between macrophages found inside a tumour and those found at the tumour margins.

Acid Phosphatase↗
PubMed1981

Combined treatment of Lewis lung carcinoma by tumor excision and levan.

A combined treatment modality including surgical excision and daily injections of high molecular levan seemed to be effective against Lewis lung carcinoma in C57BL mice. The inhibitory effect of levan on tumor growth in mice treated by resection of the primary tumor was demonstrated as follows: (1) recurrence of primary tumors was less in levan-treated mice compared to untreated animals; (2) metastases were less numerous in the levan-treated animals; (3) levan treatment partly prevented loss in body weight, and (4) it increased the survival rate. Recurrence of primary tumors appeared to be more efficiently inhibited by local levan treatment, while systemic (i.p.) administration was more effective than local treatment in preventing metastases. The mechanism of inhibition of tumor growth was related to accumulation of macrophages around the metastases.

Animals↗
PubMed1981

The effect of levan on the migration of different white blood cells across blood-vessel walls.

Nitrocellulose discs, untreated or immersed in paraffin oil or in Vespa orientalis venom, were inserted s.c. in mice. Similarly treated mice were given daily i.v. injections of levan. The discs were extracted, defibrinated, stained and the cells attached were counted. Paraffin oil and venom increased the number of monocytes on the discs. Treatment with levan reduced the number of polymorphs and giant cells, but increased the number of monocytes. Thus levan, which inhibits transendothelial migration of polymorphs, enhances the migration of monocytes.

Animals↗
PubMed1981

Effect of high molecular levan on implantation and embryonic development in mice.

Pregnant Balb C mice were treated daily with levan beginning on either the first or the ninth day of pregnancy. Damage to embryos appeared on the eighth day in mice treated from the first day. In the second group, the damage was apparent two to four days after the levan treatment was begun. In both groups the damaged and dead embryos were found side by side with apparently normal conceptuses. The damage seems to have been caused by lesions to the trophoblast since it only occurred after implantation and placentation, and it appeared to be different from the antitumoral or the graft-rejection delaying effects of levan.

Animals↗
PubMed1980

Mechanism of the inhibitory effect of levan on experimental tumors.

The mechanism of the antitumoral effect of levan was studied in the C57BL mice-Lewis lung carcinoma system. Modulation of host immune response and a direct inhibitory effect on tumor cells were found. Local treatment was more effective when begun early. It reduced tumor incidence without affecting the size of developing tumors. Systemic treatment was more effective when started late, inhibiting equally the tumor size in all mice. Macrophages are involved in local, lymphocytes possibly in systemic, inhibition. A direct effect on tumor cells was suggested by a decrease in oncogenicity, following preincubation with levan. Levan augments the antitumoral effect of cyclophosphamide in vivo and in vitro.

Animals↗
PubMed1980

Direct antitumor effect of high-molecular-weight levan on Lewis lung carcinoma cells in mice.

The polysaccharide levan exerted a direct effect on Lewis lung carcinoma cells in vitro. Tumor cells incubated with levan showed a pronounced decrease in oncogenic properties when inoculated sc in the syngeneic hosts (C57BL mice), although the viability of cells as determined by the trypan blue exclusion test was not diminished. The effect of pretreatment of inoculated mice with levan. Radiolabel incorporation into DNA, RNA, and protein was not affected in cells incubated with levan, but transport properties were selectively altered: Thymidine, uridine, and leucine transport was enhanced, whereas deoxyglucose transport was unchanged. The results indicated that levan exerted a direct antitumor effect on Lewis lung carcinoma cells in vitro.

Animals↗
PubMed1980

Blood levels of high-molecular levan in mice as a function of the route and duration of administration.

The influence of duration and of various routes of administration of native levan on blood levels of the drug was studied in mice. The blood levels varied with the doses administered. With a single i.p. injection of 20 mg levan/mouse the blood levels rose more rapidly than with higher and lower doses. In the second and third week of daily injections the rise and fall in blood levels became less pronounced. With treatment longer than 3 weeks spikes of maximal concentrations reappeared. After s.c. injections blood levels rose more slowly than after i.p. treatment. The findings indicate that: 1. high doses slow down absorption of levan; 2. after 7-21 days of treatment the RES (reticulo endothelial system) is more active in removal of levan from the blood stream than at the beginning of the treatment; 3. after treatment of 3 weeks and more the RES appears to be blocked and is again slow in the uptake of levan from the blood stream.

Animals↗
PubMed1979

Histochemical study on the pathogenesis of chlorocyclizine-induced pulmonary lipidosis.

Male rats were fed a diet containing chlorocyclizine in high concentrations for about 3 weeks. They lost weight and showed respiratory distress. The lungs contained clusters of foam cells in the alveoli. Acid esterase staining revealed reduction of activity in alveolar cells presumed to be granular pneumocytes and absence of activity in the foam cells. The lipid showed in the foam cells could not be stained with Sudan dyes, except at high temperature, and was not stained by phospholipid and cholesterol procedures. This indicated that the stored lipids are probably solid at room temperature, consisting of saturated triglycerides and/or phospholipids. It is suggested that the lipid originated in the granular pneumocytes. The drug might have deranged the esterase-phospholipase activity in these cells and in the macrophages.

Animals↗