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Neuropathologic examination of six brains from children with Hurler disease revealed nodular lesions in the glomus of choroid plexus caused by proliferation of vacuolated pericytes, fibroblasts, and arachnoid cells on the background of collagenized and myxoid stroma. This localization of lesions can be explained by the presence of a rich vascular network, as well as cellular heterogeneity greater in the glomus than in other parts of the choroid plexus or in the brain parenchyma. The development of nodules did not correlate with the age, severity of hydrocephalus, or the degree of expansion of the perivascular spaces in the brain.

Aspartylglucosaminuria (McKusick 208400) is a lysosomopathy associated with aspartylglucosaminidase (L-aspartamido-beta-N-acetylglucosamine amidohydrolase, EC 3.5.1.26) deficiency. It has been most frequently encountered in Finland, where the regional incidence may be as high as 1 in 3600 births. In North America it is very rare, having been reported in only 8 patients. We encountered 4 patients with aspartylglucosaminuria in a Canadian family of 12 siblings. The 4 siblings affected--2 brothers and 2 sisters--were apparently normal at birth; however, their developmental milestones, particularly speech, were slow, and they acquired only a simple vocabulary. Throughout life, there was a progressive coarsening of facial features; 3 had inguinal hernia and recurrent diarrhea; all became severely retarded and by the 4th decade showed evident deterioration of both cognitive and motor skills; 2 exhibited cyclical behavioural changes. Three of the siblings have died, at 33, 39 and 44 years of age. Two died of bronchopneumonia and 1 of asphyxiation following aspiration. In the urine of all 4 siblings, and in the 1 liver examined, we found 2-acetamido-1-N-(4-L-aspartyl)-2-deoxy-beta-D-glucosamine (GlcNAc-Asn) and alpha-D-mannose-(1,6)-beta-D-mannose-(1,4)-2-acetamido- 2-deoxy-beta-D-glucose-(1,4)-2-acetamido-1-N-(4-L-aspartyl)-2-deoxy-beta - D-glucosamine (Man2-GlcNAc2-Asn). Compared with the level of activity in controls, aspartylglucosaminidase activity was less than 2% in fibroblasts from 3 of the siblings, less than 0.5% in leukocytes from 1 sibling, and less than 1% in the liver of 1 sibling, whereas other acid hydrolase activities in these tissues were normal. Ultrastructural studies of skin showed that fibroblasts, endothelial cells and pericytes contained vacuoles with fine reticulo-floccular material. Glial and neuronal cells of the central nervous system showed similar inclusions as well as others composed of concentric or parallel membranous arrays intermingled with lipid droplets.

Mitochondria of fibroblasts cultured from the skin obtained at biopsy from three patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)-syndrome, one of the autosomal recessive, heritable urea cycle disorders, were studied with appropriate controls ultrastructurally. The patients were two severely retarded 10- and 12-year-old boys, and a 22-year-old sister of the former whose mental status was at the low normal range; she never had motor impairments or seizures. The mitochondria, similar in all three patients, were increased in number, very long, branching and/or "looping," and tortuous. "Spurs" or "buddings" extended from their lateral surfaces and the terminal segments were often bulbous. Other unusual configurations were also present. In addition, giant forms with large diameter contained innumerable closely-packed and parallel cristae which traversed the entire width of these mitochondria; at times they assumed a "whirled" pattern. The mitochondrial matrix was usually of high electron density. These changes were not a feature of fibroblastic mitochondria of controls. Several changes resembled those of hepatic mitochondria in this disorder. All features are interpreted as an attempt at expanding the mitochondrial volume (via structural substratum) to compensate for the metabolic incompetence of these organelles (a block in transmembranous transfer of ornithine from hyaloplasm into mitochondria for conversion to citrulline).

Hyperornithinemia, hyperammonemia and homocitrullinuria (HHH)-syndrome is a rare autosomal recessive disorder of the urea cycle, probably caused by a defect in ornithine transport across the hepatic inner mitochondrial membrane. Single rudimentary cilia were present in approximately ten percent of post-divisional or dividing fibroblasts cultured from the skin of a patient with the HHH-syndrome, whereas no such organelles were observed in dermal fibroblasts cultured from normal controls. Since single rudimentary ("primary," "oligo," "solitary") cilia have been observed in a variety of cells in animals and men but the stimuli for their formation and their significance remain controversial, a brief report on their presence in the as yet unreported condition (HHH-syndrome) was considered of interest; hopefully, it might contribute to the ultimate unravelling of some of the unresolved problems. It is of note that unlike the author's previous findings of these unusual organelles in cells affected by a pathological process (atherosclerosis), the rudimentary cilia were observed in the present instance in dividing or postdivisional cells. The implications of these (and other) observations must await further work.

Cellular localization of metallothionein (MT) in placenta may provide information on its function as a metal binding protein. Rabbit antibodies to rat liver MT cross-reacted with human MT and were used to localize MT in human term placenta by avidin-biotin peroxidase technique. Serial sections (5 microns) were cut from paraffin-embedded placentae obtained at term from five normal women and incubated with rabbit antibodies to MT. Normal rabbit serum was used as a negative control. The slides were incubated with biotinylated swine anti-rabbit IgG (linking antibody) then with avidin-biotin horseradish peroxidase complex and developed with diaminobenzidine in hydrogen peroxide (0.03 per cent) substrate. The optimum staining of MT was obtained at a 1:800 antibody dilution. MT was identified in fetal amniotic cells, syncytial trophoblasts and villous interstitial cells, and in maternal decidual cells. The presence of MT at specific cellular sites suggests that it may regulate the transplacental transport of metals such as zinc, copper and cadmium. Since the level of cadmium is lower and that of zinc and copper higher in fetal than in maternal blood, this may suggest that placental MT may restrict cadmium while enhancing zinc and copper transport.

Morphological studies of aortic fatty dots and streaks, and the adjacent normally appearing intima, in a 5 3/4-year-old boy who died of pneumonia, showed several hitherto unreported features. In lesions, lipid vacuoles and/or other cytoplasmic "inclusions" (ultrastructurally considered to present complex forms of lipids) were present on occasion in the endothelium but consistently involved the (intimal) smooth muscle cells (SMC). Similar changes were present in the adjacent intima, but were here less prominent and "tapered off" distally. A moderate number of macrophages also contained cytoplasmic lipids but such cells entirely free of lipid inclusions were observed, too. Most surprisingly, dilated and many cisternae of rough-surfaced endoplasmic reticulum (ER) in the SMC of lesions were associated spatially with cytoplasmic droplets and other forms of lipids. The results of these studies question the generally accepted central role of macrophages as being primarily involved in the pathogenesis of tissue changes in Tangier disease. It is possible that in view of the absence or paucity of high-density lipoproteins (HDL) and alterations of (their) apo A-I and apo A-II (as well as of other lipids), the arterial SMC may be in some way involved in the metabolism of the above substances in this disorder. Support of this tentative (and highly speculative) assumption must await further work utilizing tissues and cells other than those containing macrophages and other derivatives of reticulo-endothelial system.

Since its inception in 1983 the Canadian Atherosclerosis Society (CAS) has established itself firmly on the national and international scene as a forceful scientific voice. Its presence and activities have had their dominant expression at annual meetings held jointly with the Royal College of Physicians and Surgeons of Canada (RCPSC) and the Canadian Society for Clinical Investigation (CSCI) and in sponsoring other scientific and educational events, the most important of which was the Canadian Consensus Conference on Cholesterol (Ottawa, March 1988). It provided a forum for interaction between the scientific community, government, funding agencies, industry and the general public, and culminated in concrete recommendations for the populace of Canada. It also 'induced' a continuum in governmental and public concern for health with respect to atherosclerosis, and beyond it, the field of cardiovascular diseases. This dialogue continues. As a member (Constituent Society) of the International Atherosclerosis Society (IAS), the CAS has a voice in the international community, its policies and activities. The membership increase from 69 in 1983 to 175 in 1991 reflects steady growth of the CAS. The Society has been active in other areas (publications, awards for young investigators, and common educational endeavours with other groups) and will be host to the 1994 International Symposium on Atherosclerosis. Over a short period of only eight years, all of the above attests to sufficient progress (or achievement) for any scientific society. And yet, there remain quite a few areas not addressed as yet and some sad experiences (eg, that with the Long Term Planning Committee) that must be quickly remedied, if the Society is to keep pace with the everchanging emphasis in research that in the final analysis aims at improving the overall well-being and health of all Canadians. Inherent in the definition of history is the premise that accounts be provided of facts only. Historians who research their subjects derive these facts from studying the necessary accounts relating to these 'facts', using different and preferably controversial resources, so as to present the facts as objectively as possible. It is impossible, however, to fulfill all the above criteria for a historian who lived through every phase of 'life' of the subject of his or her account, because no matter how objective one wishes to remain (and bends backwards to achieve this) there will be always an element of a personal prism through which the historian lived the 'life' with his subject. For being human and thus unable to eliminate entirely that personal component, this writer asks humbly for the reader's understanding.

The three forms of origin of the atherosclerotic plaque of adults, that is, the fatty streaks, gelatinous elevations, and microthrombi, all occur in arteries of normal infants and children. Some of these may become arrested or regress, but many progress to the prominent lesions that precipitate various clinical catastrophies. The aim of modern medicine is to modify or eliminate many of the factors known to advance the atherosclerotic process and thus decrease the incidence of this disease, which ranks highest on the list of causes of morbidity and mortality in the Western world. Of these factors, some may be controlled by dietary means (low salt; low total fat and cholesterol; appropriate ratios of saturated to mono- and polyunsaturated fatty acids; high content of complex carbohydrates and fiber); controlling hypertension, diabetes, and obesity; abstaining from cigarette smoking; and vigorous physical activities. Because patterns of life-style are determined in childhood and adolescence, and because it is only during that period of life that measures to prevent progression of atherosclerosis may be predictably effective, it becomes increasingly apparent that atherosclerosis is, indeed, a pediatric problem.

Examination of a large, oedematous placenta of a still-born infant showed an extensive infiltration of chorionic villi by malignant cells; the nature of these was not apparent by light microscopy. Ultrastructural examination of these cells showed the presence of cytoplasmic granules whose size and appearance were consistent with those characteristically present in neuroblastomas. Whereas no necropsy was carried out on the still-born infant, it may be assumed, in keeping with the available data, that the placental metastases were derived from a congenital neuroblastoma. Infiltration of the villous stroma by metastatic neuroblastoma observed in the present case was not reported previously as in all other known instances the metastatic neuroblastomatous cells were confined to the lumina of the chorionic vessels.

The placenta from 30 women with diabetes mellitus were examined and weighed at delivery. Nineteen of these were from women with overt and eleven from women with gestational diabetes. Eleven placentae from normal pregnancies served as controls. There was no difference between the mean +/- s.d. placental weight for the diabetic group and the control group (609 +/- 148 versus 591 +/- 93 g, NS). The mean placental weight ratios for the diabetic group and the control group were also similar (0.98 +/- 0.23 versus 0.89 +/- 0.15, NS). Moreover, there was no difference between the weights and weight ratios of placentae from women with overt (622 +/- 173 g, 1.02 +/- 0.27) and those with gestational diabetes (586 +/- 90 g, versus 0.90 +/- 0.13). Placental weights correlated with birthweights (r = 0.70, P less than 0.01) and with skinfold thickness measurements fo the infants (r = 0.40, P less than 0.05), but neither with gestational ages (r = 0.15, NS) nor with maternal glycosylated haemoglobin levels in the third trimester (r = 0.24, NS). Among the women with overt diabetes, placental weights were greater in those in White's class B and C than those in class D and R (689 +/- 143 versus 530 +/- 177 g; P less than 0.05). In general, placentae from well controlled diabetic patients were not heavier than those from normal pregnant women, although there was an increase in placental weight in White's class B and C, as compared with those in class D and R.

Whereas the information on the subject of arterial status is sketchy and haphazard with respect to any one genetic disorder, the number of these diseases would have precluded the provision of a critical review within the scope of this presentation. Thus, it was deemed more meaningful to approach the subject selectively. A brief summary was provided on the nature of the arterial wall and its involvement in genetic diseases either as a primary target or a secondarily affected organ, and on "affinity" of various genetic disorders for a type (elastic, muscular, or smallest), segment (proximal, distal), and layer (intimal, medial, adventitial) of the arterial tree or the arterial wall, respectively. Genetic diseases may affect arteries by "causing" (a) congenital malformations, (b) alteration of the arterial "makeup" without necessarily producing definable lesions, and (c) modification of a nongenetic arterial disease (e.g., atherosclerosis), or by "producing" (d) arterial lesions that are characteristic of (even specific for?) a given genetic disorder. A few examples were selected to illustrate (b) (tuberous sclerosis; infantile GM1-gangliosidosis), (c) Wolman's disease; familial hyperlipoproteinemias), and (d) [Hurler's disease, neurofibromatosis; Ehlers-Danlos syndrome (type IV)]. Whenever available, the results of electron microscopic studies carried out in our laboratories were included. Some of these have not been reported in the literature to date. The need for a coordinated multidisciplinary approach to the study of genetic diseases in general is stressed in closing.

Ultrastructural and biochemical studies were carried out on bovine aortic smooth muscle cells cultured in the presence or absence of ascorbate. In its absence, electron microscopic examination of cultures revealed that the extracellular components consisted primarily of microfibrils. Morphologically identifiable collagen fibrils were only observed in the matrix upon ascorbate supplementation. Smooth muscle cells grown in ascorbate-free media synthesized large amounts of type VI collagen. The identity of the latter was confirmed by ion exchange chromatography, slab gel electrophoresis, and amino acid analysis. Addition of ascorbate resulted in a stimulation of type I collagen production, levels of the type III remained constant, and types V and VI were decreased. Since, in the absence of ascorbate, smooth muscle cells are known to synthesize predominantly elastin, the present data support the contention that the type VI collagen and the microfibrillar component of elastic tissue are either identical or similar.

The pathology of a case of idiopathic calcification affecting the ascending aorta in a young woman is presented. A varying width of media throughout the aorta and extending into its proximaques of calcium, found in the acellular media, were confined to the ascending aorta. No inflammatory or reparative reaction was seen in the vessel wall. Electron microscopically, the calcium seemed to have an affinity for elastic tissue elements of all sizes and the mode of deposition appeared to be by 'avenues' of the microfibrillar component. Possible pathogenetic mechanisms are discussed.

The mural thickness of fetal stem arteries of 3rd order was assessed morphometrically in 50 placentae from each of the 'toxaemia', normal pregnancy and acute fetal distress groups. Several clinical maternal and fetal variables and the syncytial sprout proliferation of the placentae were correlated with the morphometric findings. The results show that: (1) there was a significant reduction in the ratio of lumen-to-whole-diameter of the fetal arteries in 'toxaemia' as compared with the two other groups; (2) the mean lumen-to-whole-diameter ratio also differed between regions of the placenta in all groups, the most marked reduction being in the parachorial region and the least prominent in the parabasal zone; (3) no significant differences in the mean diameter ratio were found among the three sub-groups of the toxaemic pregnancies, i.e., the preeclampsia, essential hypertension and renal disease group; and (4) there was an inverse relationship between the lumen-to-whole-diameter ratios and the syncytial sprout counts in the toxaemic group.

The primary defect in patients presenting with a history of protein intolerance, mental retardation, and epilepsy of variable degree, with the unique triad of hyperornithinemia, hyperammonemia, and homocitrullinuria (the HHH syndrome) has been postulated to be a defect in translocation of ornithine into the mitochondria. In a 12-year-old boy with the HHH syndrome, the hyperammonemia observed following a protein load was prevented when the same load was given orally with a 1 mmol/kg of ornithine-HCl. At a dosage level of 0.5 to 1.0 mmol/kg/day of ornithine HCl, administered in 3 divided doses with meals, the patient's protein tolerance improved. As pretreatment hyperammonemia reverted to normal levels, the patient was able to cope with increased dietary protein and his growth accelerated. During the 2-year interval of the study, the ornithine HCl supplements were withdrawn on 2 occasions, and within a week the hyperammonemia recurred. Whereas cultured fibroblasts from the HHH patient were capable of oxidizing U-14C-glutamate to 14CO2 as rapidly as normal cells. 1-14C-ornithine or 5-14C-ornithine were oxidized at only 1/28 or 1/49 of the normal rate. Ultrastructural studies of the HHH cultured fibroblast mitochondria revealed distinctive alterations in size and shape; unusually long, branching, and "curling," HHH mitochondria also showed accelerated regressive changes.

The study of a stillborn infant and the placenta, showing extensive infiltration of fetal organs and chorionic villi by leukemic cells, is reported. The nature of the malignant cells was not apparent by light microscopic examination. Ultrastructural examination showed that these were immature myeloblasts, stressing the usefulness of electron microscopic study in establishing the diagnosis. The current case study seems to be the first in the literature in which both placenta and fetus were studied in extenso.

Ultrastructural studies of hepatic tissue obtained at biopsy from a nine year old severely retarded boy with hyperornithinemia, hyperammonemia, and homocitrullinuria showed mitochondria of bizarre shapes and unusual internal features. Among the latter were tubules extending throughout the length of the large mitochondria that on cross section had a rosette-like arrangement; the presence of a periodic, approximately 300 A thick, sievelike membrane interposed between the tubules and the inner mitochondrial membrane; and "bulges" of mitochondrial matrix occasionally formed between these two membranes. Since to be metabolized ornithine must enter the mitochondria, the hyperornithinemia is regarded as a reflection of its inability to reach the mitochondrial interior. It is speculated that among other possible causes, the unusual sievelike membrane may be the barrier to ornithine's access to the mitochondrion.

The present study was undertaken to clarify the existing controversy on the collagenous content and composition of human fibrous atherosclerotic versus normal aortic tissues. Several analytic procedures (slab gel electrophoresis; cyanogen bromide peptide mapping; high performance liquid chromatography; ion exchange chromatography) revealed that the amount of the interstitial collagens, i.e. types I and III, was similar in fibrous atherosclerotic lesions and control tissues (70% and 30% respectively). Moreover, when fibrous lesions were analyzed as serial fractions there was a uniform distribution of type I and type III throughout the lesion. Small increases in type III were observed only beneath the lesion where it interfaced with the normal media. The results suggest that contrary to some previous studies no major shifts in the ratio of the interstitial collagens are evident in atherosclerotic lesions as compared to normal intima-media preparations.

Morphological features of 3rd order, fetal stem arteries of placentae from 50 'toxemic' patients, including all types, i.e., those with pre-eclampsia, essential hypertension, and chronic renal disease, were compared with similar arteries in 50 placentae of normal pregnancies. Striking changes of the arterial wall and subtle but definite alterations in the surrounding stroma were observed in the fetal arteries from hypertensive pregnancies. The earliest mural alteration consisted of endothelial proliferation which narrowed the lumen. This was followed by proliferation of subendothelial and smooth muscle cells probably derived from the medial layer. In the media, the proliferating smooth muscle cells were affected by vacuolation and other degenerative processes. Of the above changes the intimal and medial alterations were present in 38 placentae of toxemic patients, whereas some of these features were found only in 6 cases of the control group. Other lesions of the fetal stem arteries (i.e. thrombi and arteritis) were observed less commonly. Moreover, smooth muscle cells that usually are scattered in the villous stroma in normal placentae, in toxemic patients were more numerous and tended to form bridges between the fetal arteries. On the basis of the present observations, it may be concluded that several lumen-narrowing alterations affect the fetal arteries of the placentae in toxemia of pregnancy. Whereas these undoubtedly contribute to the 'placental insufficiency' commonly found in this group of diseases, they probably represent a reaction to a more basic and as yet not identified factor(s) that may be operational in 'toxemia' of pregnancy.

Uterine smooth muscle cells in "toxemia of pregnancy" contain varying amounts of fat--a feature to date believed to characterize only the arterial smooth muscle cells in atherosclerotic lesions. Thus, the smooth muscle cells at these two sites do not differ essentially in their reactivity to certain forms of injury: hypoxia may represent an injurious factor common to both "toxemia" and atherosclerosis. These observations imply that the view that the arterial smooth muscle cells are biologically different than are those elsewhere may no longer be tenable.

Cardiac tissues obtained at post mortem examination of eight patients with the Hurler syndrome, who ranged in age from 5 to 23 years, were examined by histochemical methods and electron microscopy. Extensive myocardiocytic vacuolization and increased interstitial fibrous tissue were noted by light microscopy in all hearts. The cytoplasmic (perinuclear) vacuoles contained Luxol-fast-blue-positive substance. At the ultrastructural level, abnormal cytoplasmic organelles were present within the myocardiocytes in all patients. These organelles were of three types: zebra bodies (ZB), membranous cytoplasmic bodies (MCB) and granulomembranous bodies (GMB). As ZB and MCB are believed to represent the morphological counterpart of accumulated gangliosides, these substances rather than glycosaminoglycans appear to be stored within myocardiocytes of patients with the Hurler syndrome. The accumulation of gangliosides and the consequent damage to the myocardial substratum probably contributes to the clinically evident cardiac disease, so often observed in the patients with this disorder.

Electron microscopic studies of biopsy material from the vulva of six patients with lichen sclerosus et atrophicus and two patients with condyloma latum, and from the skin of the back and shoulder of one patient with scleromyxoedema and the forearm of one patient with macular amyloidosis revealed the presence of long spacing collagen (LSC) of one patient with macular amyloidosis revealed the presence of long spacing collagen (LSC) intermingled with an increased amount of ground substance and extracellular microfibrils. The presence of LSC in condyloma latum is believed not to have been reported previously. The LSC displayed an axial periodicity varying from 1000 to 2000 A. Our studies support the contention that the appearance of LSC is not specific of any disorder, and the formation of LSC is associated with the presence of increased amounts of glycosaminoglycan-rich ground substance and the abundance of microfilaments in the extracellular space.

According to hemodynamic theories of atherogenesis, atherosclerotic plaques are a reaction to endothelial damage caused by arterial flow disturbances such as turbulence. Earlier studies showed that hydralazine increased, whereas propranolol decreased, the product of heart rate X blood velocity, a predictor of arterial flow disturbances, and that hydralazine aggravated, whereas propranolol decreased turbulence in the region of carotid artery stenosis. This study was done to test the hypothesis that drugs which reduce arterial flow disturbances may be more effective in preventing atherosclerosis, than antihypertensive drugs which worsen arterial flow disturbances. Eighty-three New Zealand white rabbits were made hypertensive by a one-kidney Goldblatt procedure, and were fed a 1% cholesterol diet. Untreated hypertensive (P less than 0.01) and hydralazine-treated hypertensive rabbits (P less than 0.05) had significantly more atherosclerosis than did the normotensive controls; propranolol-treated rabbits did not differ significantly from the normotensive controls. Analysis of covariance showed that propranolol-treated rabbits had significantly less atherosclerosis than hydralazine-treated rabbits with blood pressure (P less than 0.04) or heart rate (P less than 0.006) as the covariates.

Peripheral leucocytes obtained from five patients with clinical histories and funduscopic findings typical of the juvenile form of the so-called neuronal ceroid lipofuscinosis (NCLF) (synonym: Spielmeyer-Vogt disease) were assayed for peroxidase activity and examined by electron microscopy. The peroxidase levels were considerably lower in three but normal in two patients. Ultrastructurally, the lymphocytes of all five patients showed the presence of tubulo-membranous cytosomes many displaying the fingerprint images at present regarded as being typical for the NCLF. The possible implications of the discrepancy between the morphological observations and the enzymatic findings are discussed.

Type V collagen is a major component of the pericellular coat of smooth cells (SMC). The purpose of the present study was to assess biochemically the nature of an in vitro interaction between bovine aortic SMC and type V collagen from the same source. This interaction was originally shown to be mediated by a cell-surface glycoconjugate. Data obtained in the present study suggests that the binding system consists of integral membrane glycoproteins which act alone or in combination with a surface glycolipid in type V attachment. The nature of this system was indicated by the finding of 80 000 and 50 000 components in the plasma membrane fractions which were specifically retained by type V collagen--Sepharose columns and incorporated both methionine and mannose label. Moreover, inhibition of protein synthesis lowered SMC attachment by 25%. The mannose label associated with these components was probably in the form of a simple oligosaccharide at the attachment site since it bound to concanavalin A (ConA) and was sensitive to endoglycosidase H. Iodinated ConA labelling indicated elevated levels of these components were associated with SMC--type V collagen interaction. The attachment region on the type V molecule was localized within the cyanogen bromide peptide 6 of the alpha 2 (V) chain.

Present studies indicate that in explants of early atherosclerotic lesions removed from aortae of young rabbits on a 1% hypercholesterolemic diet for four and seven weeks respectively, myogenic foam cells (MCF's) were capable of emigrating into the culture medium and maintained their ability to produce microfibrils, elastic tissue elements, and collagen fibrils. In explants of the smallest lesions (fatty dots and small streaks) the MFC's divided prior to, or while emigrating. At the interphase between the primary tissue and the culture medium they contained in intracytoplasmic vacuoles fragments of elastic tissue and extraneous substances which were reminiscent of cellular debris. It is possible that this phenomenon represents a true phagocytic property of the MFC's. All formed extracellular connective tissue components were also produced by the emigrated MFC's in the tissue surrounding the cellular outgrowth. In the large fatty streaks cell division was observed at the interphase between the tissue and culture medium, but not within the substance of the explant; here cellular necrosis was prominent. The fat inclusions in the MFC's of explants and the outgrowth had the appearance of conglomerateds of unorganized, and only at times concentric, membranous profiles rather than that of homogeneous droplets observed by electron microscopy in these cells in tissue sections. In the outgrowth from explants of normal aortic areas adjacent to the lesions a moderate number of smoot muscle cells contained fat inclusions; these were almost totally absent in cells of the primary aortic cultures from normal aortae. It is conceivable that the migratory and phagocytic properties of the MFC's observed in the present study relate to some aspects of regression of atherosclerotic lesions; this, however, remains highly speculative at present.

Small, round, membrane-bound electron-dense bodies were observed in the smooth muscle cells and the intimal and medial intercellular spaces of arteries in the dog, rat, and pig under normal and various experimental conditions. These structures, referred to as granulovesicular bodies (GVB), measured from 0.2 to 0.5 mum. in diameter and contained an inner core of granular and vesicular subunits. The intercellular and extracellular forms of the GVB were structurally similar, and in the interstitial spaces they appeared to have a definite spatial relation to the elements of elastic tissue. The GVB were more numerous under experimental than under normal conditions. It is speculated that the GVB are secretory in nature, originating from the smooth muscle cells, and may play a role in the remodeling of arterial elastic fibers.

The Sanfilippo Syndrome (SS) is a recessively inherited connective tissue disorder expressed in early life. It is classified as a genetic mucopolysaccharidosis (MPS) because the underlying defect involves the catabolism of heparan sulfate (HS), one of the glycosaminoglycans (GAG). Four variant forms, i.e., type A, B, C, and D, each associated with a different enzymatic defect, have been recognized in affected children. Biochemical studies show that characteristically HS accounts for most of the increased amounts of GAG excreted in the urine and those stored in viscera and brain. Gangliosides GM2, GM3 and GD2 are elevated considerably in the brain. Morphologically, the very water-soluble substances accumulating in the viscera are metachromatic, and consist ultrastructurally of finely granulo-floccular (or filamentous) material which is bound in cytoplasmic vacuoles. These substances are considered to represent the GAG. In the central nervous system (CNS) the stored substances are not soluble in water or alcohol and xylol, give a PAS-positive reaction, and stain for lipids and with luxol fast blue. Ultrastructurally, they consist of membranous arrays which often are of the "zebra body" variety. The CNS-inclusions are considered to represent the stored gangliosides; they were found also in small numbers in viscera of older children with SS. The search for a common denominator in the pathogenetic mechanism(s) culminating in both types of inclusions, continues.

"Primary" cilia were present in the endothelial cells of human aortic fatty dots and streaks but not in those of normal intima. They had the features of cilia of the "9 + 0" axonemal configuration observed in many other cells. A lateral foot process and transitional fibers "anchored" the ciliary basal body in the cytoplasm, but rootlets were not identified in material examine. Ladder-like configurations interconnected the two centrioles (= diplosome) of control endothelium. The "primary" cilia of endothelium differed from those of the rudimentary type observed in smooth muscle cells in similar lesions of man, but shared many features with cilia of those present in experimental atherosclerosis in rabbit. Cilia were rarely described in vascular endothelium. It is believed that, to date, they were not reported to occur in normal or pathological arteries in man. It is being stressed that whereas the significance of these unusual organelles remains uncertain, their widespread occurrence may indicate that their role is more important than was believed previously, and they should cease being a curiosity only.

The collagens of fibrous atherosclerotic lesions of human aortae obtained at post mortem examination were compared with those of normal intima-media preparations. Assessed quantitatively, pepsin-solubilized types IV, V and VI collagens decreased in relation to types I and III in preparations from lesions as compared to values for controls. The type V collagen in both tissues were composed of alpha 1 (V) and alpha 2 (V) chains in a 2:1 ratio. A novel ("V") collagen polypeptide identical in size to the alpha 1 (V) chain was identified in association with the interstitial collagen fraction in both tissue types. This chain had unique solubility characteristics and cyanogen bromide peptide composition. The exact relation of this polypeptide to the other collagens is not known, but it is possible that it accounts for the reported fluctuations in type V chains in aortic tissues.