SYNOPSIS. Food vacuole‐free P. multimicronucleatum and T. pyriformis readily ingest non‐nutritive Dow polystyrene latex particles (PLP) and form vacuoles containing PLP at a rate comparable to the formation of vacuoles containing bacteria. The particles aggregate within the vacuoles and are egested as balls of the size of the vacuoles. PLP containing vacuoles rapidly acquire acid phosphatase activity, which is demonstrated by histochemical (alpha‐naphthyl phosphatehexazonium salt or lead phosphate) methods as a peripheric staining. The total activity of the cell does not significantly change as a consequence of PLP uptake as suggested by the histochemical preparations and confirmed in T. pyriformis by measuring the splitting of p‐nitrophenyl phosphate at pH 5. Accordingly, no selection between nutritive and non‐nutritive particles could be revealed. The vacuole formation is induced by the mechanical action of the particles. The appearance of acid phosphatase activity in the vacuole seems to be dependent on the vacuole formation and not on its content. This early appearance of activity is due to a redistribution of the preexistent activity.

This report 1 describes the influence of natural estrogens on liver function, with special reference to sulfobromophthalein (BSP) excretion, in man. Pharmacological amounts of the hormone estradiol consistently induced alterations in BSP disposal that were shown, through the techniques of Wheeler and associates (2, 3), to result from profound depression of the hepatic secretory transport maximum (Tm) for the dye. Chromatographic analysis of plasma BSP components revealed increased amounts of BSP conjugates during estrogen as compared with control periods, implying a hormonal effect on cellular processes concerned with transport of dye from hepatocytes into biliary canaliculi. Estriol, an in vivo transformation product of estradiol, also impaired hepatic disposal of BSP in man. According to unpublished data of Hertz (4) 2 estrone, ethinyl estradiol, and equine estrogens act similarly, and it is likely that other C-18 steroids of both physiologic and synthetic origin have this property as well. These observations define a new * Submitted for publication April 13, 1964; accepted June 16, 1964. biological action of natural estrogens in man, further substantiate the role of the liver as a site of action of these hormones (5), and probably account, in part, for the impairment of BSP disposal that characterizes pregnancy (6) and the neonatal period (7-10). MethodsSteroid solutions were prepared by dissolving crystalline estradiol and estriol in a solvent vehicle containing 10% N,NDMA (N,N-dimethylacetamide) 3 in propylene glycol. Estradiol was soluble in a concentration of 100 mg per ml; estriol, in a concentration of 20 mg per ml. These, together with appropriate control solutions, were sterilized by filtration at room temperature and administered to patients by intramuscular injection. All subjects were housed on a metabolic ward during the study, and a number were maintained on fixed diets as required by concurrent investigations. The principal clinical diagnoses were rheumatoid arthritis and related connective tissue disorders. The observations reported here were made during a series of studies designed initially to examine the potential use of pharmacological amounts of natural estrogens as therapeutic or immunosuppressive (11)(12)(13) agents in man; the periods of estrogen administration therefore varied considerably from subj ect to subject. Liver function was examined in these patients by the following tests: per cent esterification of cholesterol, direct and indirect bilirubin, cephalin and thymol flocculations, thymol turbidity, prothrombin time, serum albumin and globulin, retention of BSP in plasma 45 minutes after intravenous administration of 5 mg per kg body weight, and the following serum enzymes: alkaline phosphatase, lactic dehydrogenase (LDH), glutamic pyruvic transaminase (SGPT), and glutamic oxaloacetic transaminase (SGOT). BSP infusion studies, chromatography of plasma BSP components, and liver biopsies were performed in several subjects as described below.Thirty-one patients were treated wit...

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Twenty-six women with classic or definite rheumatoid arthritis, according to the criteria of the AMERICAN RHEUMATISM ASSOCIATION, age-matched with controls were evaluated for bone mineral content and rigidity. Significant bone loss occurred in arthritics treated with corticosteroids. Bone losses at diaphyseal and metaphyseal sites were of similar magnitudesuggesting no preferential loss of trabecular bone. A significant decrease in relative ulnar rigidity was observed in patients with rheumatoid arthritis not receiving corticisteroids. An even larger decrease was noted in subjects receiving corticosteroids.Osteoporosis is commonly held to be associated with rheumatoid arthritis (1-9). Radiographic descriptions of rheumatoid arthritis frequently cite juxtaarticular and generalized bone loss as being characteristic of this disease (10-12). The etiology of the bone loss is not understood, but is attributed to multiple factors such as local inflammation, immobilization, generalized catabolic processes secondary to the disease itself, poor nutrition and the nature and duration of therapy with corticosteroids or other antiinflammatory agents. The specific role of each factor is poorly defined at present-partly be-

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