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.

Transluminal carbon dioxide-laser catheter angioplasty for dissolution of atherosclerotic plaques.

Carbon dioxide laser energy was used for the dissolution of atheromatous plaques. Flexible, nontoxic infrared optical fibers were used for the transmission of the carbon dioxide laser beam intraarterially. Dissolution of plaques and recanalization of obstructed arteries were achieved both in vitro and in vivo with controllable damage to the vessel walls.

Endocervical-type epithelium in endometrial carcinoma: a report of 10 cases with emphasis on histochemical methods for differential diagnosis.

A review of the histologic material from 100 patients with endometrial carcinoma revealed 10 cases in which endocervical-type epithelium constituted an integral component of endometrial adenocarcinoma. In nine of these, the endocervical epithelium was focal while in one patient, reported in detail, the curetted endometrial carcinoma presented as an almost pure endocervical-type lesion. In most instances, the endocervical epithelium was papillary and mature, but areas of tufting, pseudostratification and atypism were also evident. Endocervical-type epithelium in endometrial cancers was more common in curettings than in hysterectomy specimens probably because of its superficial location within the tumor. The endocervical nature of these components, which are most likely of metaplastic origin, was evident on light and electron microscopy. Histochemical stains established the similarities of the cytoplasmic mucins of these cells to that of normal endocervix and well-differentiated endocervical adenocarcinoma and emphasized the dissimilarities to the mucin content of papillary, secretory and clear-cell endometrial carcinoma. Thus, awareness of this type of lesion, application of strict histologic criteria and use of histochemical stains make it possible to reach the correct diagnosis in most cases, even in those in which the endocervical-type epithelium composes the major portion of curettings from an endometrial adenocarcinoma.

The effect of estrogen and gestagen on the mucus production of human endocervical cells: a histochemical study.

The effect of hormonal stimulation on the intracellular mucus production of the endocervical cells was histochemically and morphometrically investigated. Twenty-seven cervixes from patients who had received estrogen or gestagen prior to hysterectomy were examined. "Upper" versus "lower" cervix and "small" versus "large" crypts were compared in both groups of patients. The histochemical analysis of mucins within the cells was based mainly on the combined alcian blue/periodic acid Schiff (AB/PAS) techniques at various pH levels. A semiquantitative estimation using cell counts and statistical evaluations was done for each staining method. The results indicate that sex hormones influence the chemical composition of endocervical mucus production. In addition, the nature of the intracellular mucus varies with the cryptal size and location within the cervical canal.

Effects of various drugs on denervation changes in rat muscles.

The effects of drugs, known to affect lysosomal enzyme activities on denervated gastrocnemius muscles of rats were studied. The drugs used were: amiodarone, chloroquine, cortisone, streptomycin and trypan blue. The parameters investigated included changes in fibrillations in electromyographs, morphometric evaluations of muscle atrophy and replacement, and light and electron microscopic analysis of morphological changes and of histochemical acid phosphatase activity. All drug treatments reduced the intensity and frequency of fibrillations. Acid phosphatase spillage was best inhibited by trypan blue. Progressive muscle fiber atrophy with massive aggregation of mitochondria at the cell periphery occurred in denervated fibers. Atrophy was expressed both in loss of muscle weight and in reduction of average muscle fiber diameter. Administration of all the drugs resulted in slowing down of muscle weight loss, particularly 30 days after denervation. All drugs induced slowing down of the loss in average fiber diameter on day 3 after denervation, while on day 10 only cortisone and amiodarone still exerted this effect. A similar transitory slowing of denervation changes was observed in estimations of replacement of muscle by collagen and adipose tissue. Only the effect of trypan blue and amiodarone persisted on day 10. The results indicate that drugs known to inhibit lysosomal enzyme activity may slow down the denervation-derived muscle atrophy to a certain extent, but the effects are transitory.

Experimentally produced hypertension and aortic acid esterase.

The effect of hypertension, which is known to enhance atherosclerosis, on acid esterase activity of rat aortic wall was studied histochemically. The purpose was to test our notion that atherogenesis depends on the balance between supply of lipids to the arterial smooth muscle cells and the lysosomal esterase activities. Hypertension was produced in rats by unilateral nephrectomy and administration of desoxycorticosterone acetate and sodium chloride. The animals reacted with varying degrees of hypertension. In rats with hypertension of a sufficiently high degree and of long duration, inhibition of aortic acid esterase activities occurred. No inhibition of these enzymes occurred in the other organs examined.

The effects of varying lengths and powers of CO2 laser pulses transmitted through an optical fiber on atherosclerotic plaques.

We have studied the changes induced in atherosclerotic arteries by a CO2 laser beam delivered through a silver halide optical fiber. We found that the crater depth and diameter correlate with the total energy delivered and with the mode of delivery. Short-duration high-power pulses caused shallower and narrower craters and less damage to the arterial wall compared to the same energy delivered as low-power pulses of long duration. Thus, high-power pulses for short periods may be an effective and safe procedure for evaporization of atherosclerotic plaques.

The pituitary-thyroid axis effects on ocular and orbital tissues: a histological, histochemical, and morphometric study.

This work tests the notion that the effect of thyroid hormone on orbital and ocular tissues is mediated through its action on their lysosomal enzymes. Hyperthyroidism was produced in guinea pigs by thyroxin and TSH; hypothyroidism was induced by thiouracil. After treatment for 10 to 21 days, several ocular and orbital tissues were taken for histological, morphometrical, and histochemical examinations. High acid phosphatase activity was demonstrated in extraocular muscles, optic nerve and the retinal pigment epithelium of thyroxine- and TSH-treated animals. The findings fit the notion that the effects of thyroid hormones are mediated through lysosomes also in ocular and orbital tissues.

Reappraisal of the role of macrophages in the pathogenesis of atherosclerosis.

New Zealand rabbits were fed an atherogenic diet, 8 with and 8 without twice weekly intravenous injections of GdCl2. The injections caused a reduction in the phagocytic activity of the reticuloendothelial system by one fourth to one half. No significant differences were found between the two groups in the planimetric extent of atheromata in the aortae. GdCl2 treatment inhibited the deposition of sudanophilic lipids in depth of the arterial wall. The findings indicate that macrophages are the primary foam cells and their uptake of lipoproteins is essential for the deposition of lipids in myocytes. Lipid-laden myocytes and ground substance mucopolysaccharides represent sinks in which lipids are removed from the flow and accumulate locally.

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.

Congenital bronchiolitis obliterans.

A case is described of intrauterine pneumonia with "Congenital Bronchiolitis Obliterans" in a premature infant who died 35 hours after delivery. The patient presented from birth with increasingly severe respiratory insufficiency. Post-mortem histological examination of the lung revealed obliterative bronchiolitis, a rare disease which the patient most probably developed in utero. Only two other similar cases of congenital obliterative bronchiolitis have been reported in the literature, both with obscure etiology. A detailed pathological description of pulmonary changes is given and the literature is reviewed.

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.

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.

Acid esterase activity in the pathogenesis of atherosclerosis: effect of partial aortic ligation in rabbits.

Partial ligation of the aortas of rabbits below the ostia of the renal arteries resulted in a proliferative intimal reaction. Myocytes in the media of the ligated area showed little or no acid esterase activity. This reduction in acid esterase activity is believed to play an important role in atherogenesis.

The role of nerve lysosomal enzymes in the pathogenesis of denervation atrophy. Electromyographic and histochemical study in rats.

Section of sciatic nerves of rats produced fibrillations within 3 days. Foci of hyalination leading to necrosis corresponded to segments of muscles containing end plates. The electrolyte content, mainly Ca, was increased, NADH2-TR activity was decreased and membrane ATP-ase was increased. The known increase in hydrolytic enzyme activities in denervated muscles was due to spilling of lysosomal enzymes from degenerating axons at the myoneural junction. This explains the discrepancy between morphological studies indicating paucity of lysosomes in normal muscles and the high hydrolytic enzyme activities in denervation. We propose that denervation changes are at least partly due to the effect of lysosomal spillage from degenerating axons.

Unusual ovarian, tubal and pelvic mesothelial inclusions in patients with endometriosis.

Unusual mesothelial inclusions were observed in ovaries, fallopian tubes and pelvic wall in six out of 57 patients with endometriosis and in none of 100 ovaries without endometriosis. Although of the same origin as the common ovarian epithelial inclusion cysts, these mesothelial inclusions were different being small, closely packed mesothelial cell nests with or without central lumina and occasionally demonstrating a pseudoinfiltrative pattern, rather than the cystically dilated, non-crowded glands lined by a variety of Müllerian type epithelia. Histochemical reactions of these mesothelial inclusions were similar to those obtained in normal mesothelium, but differed from those seen in common epithelial inclusion cysts, endometriosis and adenocarcinoma. The association of these inclusions with endometriosis suggests that a common stimulus is responsible for the development of both conditions from the multipotential pelvic mesothelium.