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Six subjects from three sibships with hyperornithinemia, homocitrullinuria, and hyperammonemia are described. Assays of liver biopsy in one showed decreased CPS I and leukocyte assays indicate a similar defect in all six. Loading studies with ornithine and citrulline are consistent with a block early in the urea cycle between ornithine and citrulline. They thus support the results of the enzymatic assays. Similar studies with lysine and homocitrulline indicate there is excessive homocitrulline biosynthesis that is related to lysine intake, but there is no evidence of a block in the main lysine catabolic pathway. The younger more severely affected patients require protein restriction to 1.2 and 1.5 g/kg/24 hr to control hyperammonemia; hyperornithinemia remains unaffected. Adult subjects avoid large protein meals but tolerate a diet that is almost normal. The mode of inheritance of this disorder appears to be autosomal recessive. The fine structure of liver shows the presence of large and abnormally configurated mitochondria. There is a peculiar periodic structure situated closely to the inner mitochondrial membrane, and it is possible that the presence of this may be related to the impairment of transport of ornithine into the mitochondria; this in turn may give rise to hyperornithinemia. This disorder adds to the metabolic errors that suggest that there are close links of lysine metabolism to the urea cycle but the details are yet to be defined.

A pilot study was carried out to test whether normal human aorta and aortic atherosclerotic lesions obtained at post-mortem examination were suitable for the demonstration of proteoglycans (PGs) by ruthenium red (RR) staining, and whether by this method qualitative and quantitative differences of PGs might be detectable in various types of lesions and between lesions and the normal aortic intima. The results indicate that the PGs of the above tissues obtained at post mortem were clearly visualized by electron microscopy using the RR-indicator and were thus suitable for quantitative and qualitative evaluation. Of the RR-positive granules only those 20 nm and larger were assessed. RR-granules measuring 20-50 nm were present in normal intima and media, in increased concentration in the innermost part of the mixed fatty-gelatinous lesion, and in a decreased concentration in the fibrous cap of an atherosclerotic plaque. The same RR-granules were observed in a fatty streak and in addition 50-100 nm granules were present in this type of lesion; the overall RR-granule-concentration was reduced here. Granules of both sizes were interconnected by filamentous network. The differential presence of the large (and hitherto unreported) as well as the smaller granules in the various lesions is briefly discussed in the light of the present-day knowledge of tissue-PGs, and the importance of an examination in situ of the compound PGs-complexes in their native form, is emphasized.

Single rudimentary cilia were observed by electron microscopy in smooth muscle cells (SMCs) of aortic fatty streaks in hypercholesterolemic rabbits, but not in aortae of controls. Similar cilia are known to occur in several tissues and various species, but it is believed that they have not so far been identified in the SMCs of atherosclerotic lesions. These cilia differ structurally from the classical type characterising ciliated epithelium. It is currently thought that a sudden transformation from mitotic replicative to nonmitotic structuring tissue may be correlated with the disappearance of centrioles and formation of cilia. The possible implications of the above concept in the overall process of atherosclerosis in the context of our present-day knowledge is briefly discussed.

A 4 1/2-year-old boy with a history of recurring respiratory tract infections and seizures, and evidence of severe retardation of psychomotor development and growth, lacked the coarse facial features, skeletal changes and other clinical stigmata generally associated with mannosidosis, but the total alpha-mannosidase activity in his leukocytes, cultured fibroblasts and liver were no more than 10% of the control mean. Studies of the residual alpha-mannosidase enzyme suggest a specific deficiency of the thermostable isoenzyme with an acidic pH optimum. The alpha-mannosidase in the fibroblasts of our and another (control) patient with mannosidosis had a reduced affinity for the substrate 4-methylumbelliferyl-alpha-D-mannoside. Light microscopy of the liver biopsy showed an increase in connective tissue often distorting the hepatic architecture; numerous tiny vacuoles, small dense and lipid bodies in most hepatocytes, and similar but more extensive changes in sinusoidal cells; and sinusoidal pools of hepatocytic debris. Electron microscopy of hepatocytes revealed vacuoles similar but not identical to those described in reported mannosidosis patients, and in addition several forms of secondary lysosomes; prominent peroxisomes (microbodies); increased numbers of profiles of smooth endoplasmic reticulum; dilated rough endoplasmic reticulum containing traces of fine granulo-fibrillar material; increased numbers of rosettes of alpha particles of glycogen and reduced numbers of mitochondria with alterations in their distribution, size and configuration. It is believed that the usual clinical and hepatic ultrastructural features in our patient reflect another variant of mannosidosis.

Hypertension may be considered a disorder of increased energy in the blood, with two components: increased pressure energy may promote arteriolar disease, whereas arterial diseases such as atherosclerosis may be more closely related to flow disturbances (turbulence, boundary layer separation, high shear, or axial stream impingement) due to increased kinetic energy. Previous studies have shown that hydralazine aggravates turbulence in stenosed carotid arteries, whereas propranolol diminishes turbulence. To assess the effect of these drugs on the progression of atherosclerosis, the drugs were administered subcutaneously to rabbits made hypertensive (one kidney Goldblatt) and hypercholesterolemic (1% cholesterol diet for 4 weeks). Appropriate controls with normal, only hypertensive and hypertensive-hypercholesterolemic untreated rabbits were employed. A total of 36 rabbits was used. The extent of the aortic surface involvement with atherosclerotic lesions was assessed by morphometric analysis of magnified photographs. Although the extent or surface involvement did not differ significantly between the untreated or treated hypertensive rabbits, there was an interesting difference in the relationship between blood pressure and extent of surface involvement. In the untreated and hydralazine treated rabbits, there was a direct correlation between increasing blood pressure and extent of lesions; in the propranolol treated group, this relationship was abolished.

One or two rudimentary cilia were observed by electron microscopy in smooth muscle cells (SMCs) of fatty dots and streaks, but not in normal intima of human aorta. Similar organelles are known to occur in many cell types and various species, but to the best of the author's knowledge, have never been found in the SMCs of arterial or other tissues of man in health and disease; recently, they were reported to be present in the SMCs of experimental atherosclerosis in rabbits. The rudimentary cilia observed in this study had a "9 + 0" axoneme (microtubular complex) and differed also in other aspects from the classical cilia. Semiserial sections of SMCs containing a diplosome disclosed that on several occasions both of its constituent centrioles gave rise to rudimentary cilia. SMCs containing cilia or their basal bodies were observed more often in the human than in experimental atherosclerotic lesions. Whereas the function and significance of the rudimentary cilia remain largely unknown, the current theory proposes that a sudden transformation from a mitotic replicative to a nonmitotic structured tissue "diverts" centrioles to the formation of these unusual organelles. It is conceivable that rudimentary cilia could serve as morphological indicators of aborted mitosis in human atherosclerotic lesions.

Collagenous components were extracted from bovine aorta by pepsin digestion. Differential salt precipitations separated the interstitial from the basement membrane (BM) collagens, and the latter were subsequently separated into three distinct types. Ion exchange chromatography, SDS-slab gel electrophoresis, cyanogen bromide and protease V8 peptide mapping, and amino acid analysis were used to characterize the component chains within each of these types. The major BM-class contained three distinct chains which were identical to the alpha 1(V), alpha 2(V) and alpha 3(V) chains of type V collagen from normal human placenta. The stoichiometry of the chains suggests a [alpha 1(V)]2 alpha 2(V)-helical organization, but the role of the alpha 3(V) chain in the overall structural organization of collagen V remains unknown. The second BM-class contained a heterogeneous group of molecules ranging in size from 40 000 to 140 000 daltons. Two predominant chains within this group were characterized as the alpha 1(IV) and alpha 2(IV) chains of type IV collagen. The last class of BM collagens consisted primarily of high molecular weight components; upon reduction these gave rise to two low molecular weight collagenous species (40 K and 45 K) characteristic of type VI, low molecular weight or 'linker' collagens. The functional roles of the isolated BM collagens, either individually or collectively, has not been ascertained to date.

Yellow pulmonary hyaline membranes were observed at autopsy in 16 newborn infants between 1972 and 1974 in four hospitals of Philadelphia, Pa., and Newark, N.J. Other pediatric pathologists in this country and in Spain have seen the same lesion within the last decade. Chemical analysis of affected lung tissue, histochemistry, and electron microscopy show the yellow color to be due to the presence of bilirubin. No substantial clues concerning the basic etiology or mechanism for the formation of these unique membranes emerge from a detailed review of clinical and postmortem data nor from comparison of these data with those for 68 control infants with the usual acidophilic pulmonary hyaline membranes. We are left, however, with the impression that prolongation of life, relatively elevated levels of serum bilirubin, and protracted assisted ventilation (with either CPAP or PEEP) are intimately related to their formation.

A study to assess chromosomal damage in persons with acute viral diseases was undertaken in view of conflicting reports in the literature concerning such damage. Forty children with measles, mumps, and chickenpox, or who had received measles vaccine, were investigated and compared with a control group of 12 children. No greater incidence of chromosomal abnormalities was found in the study group than in the control group.