Ultrastructure of the Liver in the Cerebrohepatorenal Syndrome of Zellweger

Three infants with clinical and biochemical features of Zellweger's cerebrohepatorenal syndrome are presented, and the ultrastructural features of successive biopsy and autopsy liver specimens are described. No hepatocellular peroxisomes were found in these patients on routine electron microscopy or electron microscopic histochemistry. In a control group of liver biopsies from 9 patients with other pediatric liver diseases, peroxisomes were readily identifiable in each hepatocyte. Apart from the absence of peroxisomes, the hepatocytes had a remarkably “normal” aspect, even in the final stages of the disease. Mitochondrial abnormalities, which have been the subject of some controversy in this syndrome, were a highly variable and inconstant finding in our cases.

We draw attention to another ultrastructural feature of the syndrome, namely the occurrence of large angulate lysosomes, containing conspicuous double lamellae, inside macrophages, which were especially abundant in later stages of the disease. These angulate lysosomes may be of additional value in the ultrastructural diagnosis of Zellweger's syndrome, especially when only poorly preserved liver tissue (e.g., paraffin-embedded or postmortem material) is available, and the absence of peroxisomes is difficult to assess. In these instances, the angulate lysosomes can still be identified with ease.     

Angulate Lysosomes

Under many circumstances, macrophages accumulate lipids (possibly in combination with other materials) in the form of micelles that by their rigidity and size impart an irregular, angulate shape to the lysosomes in which they are stored. When macrophages contain large numbers of these angulate lysosomes, they have a characteristic light microscopic appearance and are often designated Gaucher cells or Gaucher-like cells. In most instances, however, the angulate lysosomes are small in number or size and are not easily recognized by light microscopy.

A search of the literature and our own files revealed angulate lysosomes in a considerable number of conditions in which they have not previously been observed or recognized. In most conditions, the evidence indicates that the material stored is derived from phagocytosed cells that are incompletely digested, either because they are simply too numerous to be handled by the macrophage or due to a primary metabolic deficiency, or both. In contrast to what has been assumed, angulate lysosomes not only arise in situations in which blood cells are phagocytosed, but also when various types of degenerating tumor cells, remnants of myelin sheaths, or bacteria accumulate inside macrophages. In yet other conditions, the origin of the lysosomal contents remains to be elucidated.     

Angulate Lysosomes

Under many circumstances, macrophages accumulate lipids (possibly in combination with other materials) in the form of micelles that by their rigidity and size impart an irregular, angulate shape to the lysosomes in which they are stored. When macrophages contain large numbers of these angulate lysosomes, they have a characteristic light microscopic appearance and are often designated Gaucher cells or Gaucher-like cells. In most instances, however, the angulate lysosomes are small in number or size and are not easily recognized by light microscopy.

A search of the literature and our own files revealed angulate lysosomes in a considerable number of conditions in which they have not previously been observed or recognized. In most conditions, the evidence indicates that the material stored is derived from phagocytosed cells that are incompletely digested, either because they are simply too numerous to be handled by the macrophage or due to a primary metabolic deficiency, or both. In contrast to what has been assumed, angulate lysosomes not only arise in situations in which blood cells are phagocytosed, but also when various types of degenerating tumor cells, remnants of myelin sheaths, or bacteria accumulate inside macrophages. In yet other conditions, the origin of the lysosomal contents remains to be elucidated.     

The cerebrohepatorenal syndrome of Zellweger,morphologic and metabolic aspects

The cerebrohepatorenal syndrome of Zellweger (CHRS) is remarkable not only for a distinctive combination of congenital anomalies, but also for an unusual variety of profound metabolic disturbances. After a discussion of the clinical diagnosis of CHRS, abnormalities in the metabolism of peroxisomes, mitochondria, iron, pipecolic acid, glycogen, bile acids, and organic acids are discussed and related to the clinical and other biochemical findings in the syndrome. Attention is also drawn to syndromes with biochemical or clinical abnormalities similar to those of CHRS. Although the biochemical findings indicate major abnormalities in oxidative metabolism, the primary defect remains obscure.     

Ultrastructural and Immunocytochemical Study of a Primary Gastrinoma of the Liver

A primary hepatic gastrinoma found in a 13-year-old boy was studied by light microscopy, immunohistochemistry, electron microscopy, and immunoelectron microscopy. Results were consistent with a neuroendocrine neoplasm with abundant gastrin-immunoreactive cells. Unlike all previously reported cases of primary hepatic neuroendocrine tumors, which have been endocrinologically asymptomatic, the patient had a Zollinger-Ellison syndrome apparently cured by surgical resection of the tumor.     

New diagnostic algorithm for detection of covert Bow Hunter's Syndrome

Bow hunter''s syndrome (BHS) should not be overlooked as a cause of cerebral infarction in the posterior circulation. However, covert BHS, which does not impair blood flow with simple rotation but only at certain angles, may make the diagnosis of BHS difficult. We propose a new algorithm to detect BHS or covert BHS. We recommend that BHS and covert BHS be detected by noninvasive duplex ultrasonography, which will allow for appropriate treatment.     

Oral and maxillofacial considerations in Gardner's Syndrome

Gardner's Syndrome is a variant of familial adenomatosis polyposis (FAP) with a triad consisting of polyps of the colon, multiple osteomas and surface tumors of soft and hard tissue. The intestinal polyps have a %100 risk of undergoing malignant transformation, therefore early identification of this disease is very important. There are several symptoms of Gardner's syndrome in the oral and maxillofacial surgery, which can be discovered during routine dental examination. We report a case of a 25-year old male patient with Gardner's syndrome who has not any intestinal polyps but osteomas in the mandible and jaw deformalities.     

Effect of dilysosomal macrophages on development and outcome of pneumonia caused by the agent of enzootic abortion in ewes

Repeated intranasal injection of the bacterial lipopolysaccharide pyrogenal leads to the accumulation of numerous macrophages packed with lysosomes of leukocytes in the hilar and apical zones of the lungs in mice. Dilysosomal macrophages increase the level of resistance of the mice to the agent of enzootic abortion in ewes (AE) and thus converta lethal infection into a nonlethal disease.Laboratory of Pyrogens and Nonspecific Resistance, Department of General Pathology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 4, pp. 440–442, April, 1976.     

Liver sinusoidal cell ultrastructure in partially hepatectomized rats

Two-thirds of the liver was removed from male Wistar rats weighing 160–200 g. In response to the operation phasic changes occurred in the structure of the lysosomal apparatus in the Kupffer cells. The number of primary lysosomes in the Kupffer cells was increased 2.5 h after partial hepatectomy, and the size and polymorphism of the lysosomes were increased after 9 h. At the peak of mitotic activity of the hepatocytes (30 h after partial hepatectomy) mainly secondary lysosomes were identified in the Kupffer cells, but 48 h after the operation, on the other hand, their number was reduced, although young forms of primary lysosomes appeared. Manifestations of fatty infiltration predominated in the endothelial cells and reached a maximum at the peak of mitosis of the hepatocytes. The results are evidence that ultrastructural changes in the sinusoidal cells depend on the phases of reparative regeneration of the liver.Laboratory of Pathophysiology, Department of General Pathology, Institute of Clinical and Experimental Medicine, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences of the USSR V. P. Kaznacheev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 12, pp. 729–733, December, 1979.     

Ultrastructure of the jejunal mucosa in human immunodeficiency virus infection

The ultrastructural changes in the jejunal mucosa of 11 male patients, three with clinical AIDS, five with AIDS related complex-progressive generalized lymphadenopathy (ARC-PGL), and three who were only HIV antibody positive, were studied. In the enterocytes, major abnormalities were proliferation of smooth endoplasmic reticulum mitochondrial changes, vacuolization of cells, and fat hold up. In the lamina propria, degeneration of enteric nerve axons and smooth muscle were seen. Microvasculature showed both endothelial cell degeneration and hyperplasia. The presence of tubuloreticular inclusions in endothelial cells paralleled the stage of the disease. Since none of the 11 patients had any opportunistic infection, these changes are likely to be the effect of HIV infection.     

Effect of Ivermectin on Function of Liver Macrophages

Ivermectin had no effect on phagocytic function of liver macrophages, but blocked LPS-induced secretion of tumor necrosis factor, NO, prostaglandin E2, and increase of intracellular concentration of Ca2+. These inhibitory effects were observed only in the presence of chlorine ions in the extracellular medium, which attested to involvement of glycine-dependent chlorine channels.     

家兔肝脏淋巴液生成机制的超微结构研究

目的为探讨肝脏淋巴液的生成机制,研究了家兔肝脏毛细淋巴管的超微结构特点,并测量了有关数据。方法半薄切片光镜观察,超薄切片透射电镜观察,计算机图像分析。结果内皮细胞中含有大量的质膜小泡,小胞的数密度为44.16±4.0个/μm3,体密度为0.0489±0.0038,小泡的平均直径为109.63±1.93nm。内皮细胞间的连接方式有3种,即插入连接(33.7%)、重叠连接(53.9%)和端端连接(12.4%);处于开放状态的占1.1%;内皮细胞连接处有特殊连接装置的占53.9%。结论在肝脏淋巴液的生成机制中,毛细淋巴管内皮细胞的转运功能可能是以质膜小泡的运输为主,内皮细胞间连接所形成的通道作用为辅。     

Ultrastructure of liver progenitor/oval cells in children with nonalcoholic steatohepatitis

PurposeVery interesting reports have appeared lately on the role of liver progenitor/oval cells in the morphogenesis and development of nonalcoholic steatohepatits (NASH) in adult patients and experimental animals. However, no literature data concerning pediatric patients have been available. Therefore, the purpose of the study was to evaluate the ultrastructure of the population of liver progenitor/oval cells in the biopsy material from children with previously clinocopathologically diagnosed NASH.Material/MethodsElectron-microscopic examinations were conducted on fresh tissue samples collected from 10 children with NASH (aged 2–14 years), which were fixed with a solution of 2% paraformaldehyde and 2.5% glutaraldehyde in 0.1 M cacodylate buffer.ResultsUltrastructural examinations of the liver progenitor/oval cells in children with NASH show a quite prominent number of these cells, especially their two types, hepatic progenitor cells (HPCs) and intermediate hepatocyte-like cells (IHCs), with intermediate bile-like cells being the least frequent. They were found to occur single or in clusters of two, seldom of three, and frequently in the areas of advanced liver fibrosis or close to them. Many times, these cells were accompanied by hepatocytes showing a varying degree of death, to total cell disintegration. Interesting was the presence of activated nonparenchymal liver cells, i.e. Kupffer cells/macrophages and hepatic stellate cells, frequently found to adhere to the hepatic oval cells.ConclusionsThe current study suggests a marked involvement of the population of liver progenitor/oval cells, mainly HPCs and IHCs, in the development of nonalcoholic steatohepatitis in pediatric patients, especially in fibrosis progression.     

Importance of Annulate Bodies in the Diagnosis of Granular Cell Tumors (Schwannomas)

Granular cell tumors (GCTs) were originally characterized ultrastructurally by the presence of many large lysosomes and angulate bodies (ABs). ABs appear to have been forgotten, and the diagnosis of GCT currently depends solely upon the presence of large lysosomes. Most investigators favor a Schwann cell origin for GCT. Recently, reports of granular tumors with large lysosomes but without ABs have suggested other cells of origin. If the ultrastructural criteria for the diagnosis of GCT were maintained as originally described, many of these granular tumors would not qualify as true GCTs. Two granular tumors that were at first considered GCTs are described. Based on the presence of large lysosomes and the presence or absence of ABs, one tumor was considered a true malignant GCT and the other a benign fibroblastic tumor.     

Ultrastructure of Sinusoidal Cells in a Benign Liver Cell Adenoma

A typical benign liver cell adenoma was removed from a 25-year-old female taking an oral contraceptive. The biopsy was perfusion-fixed, allowing good visualization of sinusoids and sinusoidal cells. Kupffer cells were seldom seen. Endothelial cells were of irregular thickness; most of them had few fenestrae and were attached to each other by well visible junctions. Normal perisinusoidal cells (PSC) were not seen but were replaced by myofibroblast-like cells with thick subendothelial processes. A basement membrane often underlaid endothelial cells and the processes of PSC. The enlarged Disse space with a flattened sinusoidal hepatocyte membrane contained occasional red blood cells and an abundant extracellular matrix but few collagen fibers. These sinusoidal abnormalities leading to the capillarization of sinusoids, either the cause or the consequence of the disease, indicated a loss of normal hepatocyte homeostasis.     

Microvesicular Fatty Liver in Rats with Resembling Reye's Syndrome Induced by 4-Pentenoic Acid

To produce an animal model of Reye's syndrome (RS), 20 adult male Wistar rats were given 10 repeated i.p. injections of 50 mg/kg 4-pentenoic acid (PA) each separated by an 8-h interval. Then, 90min after the tenth dose, they were given a final i.p. injection of 150 mg/kg PA. Thirteen control animals were injected with vehicle only using the same time schedule. More than half the animals in each group were fed a common diet, but the others were fasted during the terminal 10-h stage. All rats were sacrificed 30 min after the last injection. At the terminal stage, in comparison with the vehicle-injected controls, hypolipemia, hypoglycemia and high titers of serum ammonia and urea N were estimated significantly in the PA treated rats fed throughout the whole period. Hypolipemia and hypoglycemia were more prominent in the terminally fasted group than the group fed continuously. Only in the PA-treated rats fed throughout the whole period moderate morphological signs of microvesicular fatty liver were exhibited. Ultracytochemical findings and biochemical determinations showed that the major lipids in the microvesicular fatty livers were triglycerides. Morphometric analysis revealed distinct hepatic mitochondrial swelling in the PA-treated rats. Therefore, the above treatment with PA was able to induce microvesicular fatty liver in rats with resembling RS, which were fed throughout the treatment procedure, but not in the terminally fasted rats.     

Dental Findings in Cornelia De Lange Syndrome

Cornelia de Lange syndrome is a congenital disease, basically characterized by psychomotor retardation associated with a series of malformations, including mainly skeletal, craniofacial deformities together with gastrointestinal and cardiac malformations. There is no definitive biochemical or chromosomal marker for the prenatal diagnosis of this syndrome. We actually want to present the case of a 10-year-old patient, who was admitted to our clinic for dental pain. The patient had the symptoms of Cornelia de Lange syndrome. During the oral examination of this patient, the patient was found to have the typical symptoms of Cornelia de Lange syndrome, such as micrognathia and delayed eruption in conjunction with the symptoms of the Hutchinson''s syndrome, which had never been reported before.