Vacuolated lymphocytes

Mental and motor deterioration accumulation of mucopolysaccharides is as significant as accumulation of gangliosides invariably fatal autosomal recessive blindness, cherry red macula (30%) hepatosplenomegaly vacuolated lymphocytes startle response to sound, dysostosis multiplex. 

Mental retardation Visceromegaly Vacuolated lymphocytes foamy histiocytes Hurler-like phenotype ... 

Atrophy of the optic nerve appears to be a consistent finding. Pigmented macular protrusions have been observed by Hagbbrg et al. (1965). The spinal fiuid was found to be clear and colorless (Brown et al. 1954), and cells were not increased. Spinal fiuid protein was initially elevated (480 mg%) and later normal (51.3 mg%) in the case of Hagberg et al. The electroencephalogram in this patient showed lack of the normal basal rythmic activity and cortical activity. Ventriculography revealed marked dilatation of the ventricles with paper-thin walls and signs of underdevelopment of the cerebellum. Routine laboratory examinations were normal. Vacuolized lymphocytes were not seen. 

A rather typical finding is that of vacuolated lymphocytes, first detected by Bagh and Hortling (1948) and confirmed by a number of others (Rayner 1952, Nissen 1954, Stubbe-Teglbjaerg and Plum 1955, Gilje and Nissen 1956, JuLiAO et al. 1957, Friedrich 1957, Harlem 1960). However, vacuolation of lymphocytes was not seen in any of the ten cases from the U.S.A. (Jervis 1959), and in another case (Hoffmann 1957) which likewise was not from Scandinavia. 

Stubbe-Teglb JAERG, H. P., and C. M. Plum Vacuolized lymphocytes in lipidosis. Acta neurol. scand. 30, 327 (1955). 

In mucolipidosis I patients, vacuolated lymphocytes and foamy bone marrow cells are common. Cellular vacuolation is often seen in the enlarged liver (more extensive in the Kupffer cells than in the hepatocytes) and spleen, CNS neurons, peripheral nerves, and the neurons in the myenteric plexus. Pathology is generally milder in the late-onset cherry-red spot-myoclonus form than in the more severe mucolipidosis I and is confined to the nervous system. CNS neurons prominently contain lipofuscin pigments. 

Miller Scott (1985) reported marked reduction in thymus weight in rats fed dioctyltin dichloride for 8 or 12 weeks at a level of 75 mg/kg diet. Numbers of lymphocytes together with T cell subpopulations were reduced in treated rats, but no difference was seen in antibody response to sheep red blood cells in vivo. No evidence was foimd of in vitro cytocidal effects of dioctyltin dichloride on blood lymphocytes. Evans et al. (1986) dosed pregnant and non-pregnant rats for 3 weeks at 75 mg/kg diet and reported severe thymic atrophy and extensive vacuolation of reticuloendothelial cells in pregnant animals only. 

Mitochondrial ATPase inhibition. Smoke extract, in the mouse brain mitochondria culture in the presence or absence of vitamin C for 60 minutes, inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner. The effect of extract on mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. The extract treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane was preserved. Nicotine produced no significant damage . Mitogenic activity. Water extract of the dried leaf, administered to mice at a concentration of 0.05%, was active on lymphocytes from mesenteric lymph node and lymphocytes B and T. Intracellular Ca level was unchanged. The extract was active on... 

The lysosomal disorder SASD is characterized by accumulation of the free acid monosaccharide sialic acid in the lysosomal compartment of the cell. Diagnosis is based on the demonstration of abnormal excretion of free, not OGS-bound sialic acid in urine, coupled with accumulation of free sialic acid in cultured fibroblasts, and on microscopic evidence of vacuoles (increased and swollen lysosomes filled with light electron-lucent material in skin biopsy and peripheral blood lymphocytes). The inheritance is autosomal recessive. There are different clinical forms of this disorder an adult form, called Salla disease (SD) or Finnish sialuria (OMIM 604369) infantile SASD (ISSD OMIM 269920) and an intermediate form, severe Salla disease [3,16]. 

The mechanism of action of the immunological and anti-inflammatory effects of antimalarials include inhibition of phospholipase A, inhibition of platelet aggregation, a range of lysosomal effects (e.g., an increase in pH, membrane stabilization, and inhibition of release and activity of lysosomal enzymes), inhibition of phagocytosis, an increase in intracellular pH in cytoplasmic vacuoles leading to decreased stimulation of autoimmune CD4 T cells, decreased cytokine release from lymphocytes and stimulated monocytes, inhibition of immune complex formation, and antioxidant activity. In patients with porphyria cutanea tarda, chloroquine and hydroxychloroquine bind to porphyrins and/or iron to facilitate their hepatic clearance. The ability to bind to melanin and other pigments may contribute to the retinal toxicity seen occasionally when anti-malarial agents are used. 

The ultramicrostructural alterations of the thyroid caused by overdosed iodine included a decrease of microvilli, dilation of rough endoplasmic reticulum, vacuolation of mitochondria, an increase in peroxidates and secondary lyso-somes, an increase in myelin-sheath structures in cytoplasm, and apoptosis and necrosis of thyroid epithelial cells. In contrast to Wistar rats, iodine excess could also cause infiltration of lymphocytes and proliferation of fibrous tissue in NOD. H-2 mice, which showed a positive correlation with the iodine dose. Similar results were found in other susceptible animals (Li et ai, 1993 Bagchi et at, 1995). When human thyroid cells were cultured with excessive iodine in vitro, Many et al. (1992) observed the same phenomenon under the electron microscope, such as dilated mitochondria, rough endoplasmic reticulum, increased secondary lysosomes, apoptosis and necrosis of epithelial cells, and a positive correlation between the ratio of apoptosis and iodine. 

Figure 68. Autophagy. Under lymphocyte attack, human sarcoma cells extensively vacuolized their cytoplasm, but remained metabolically alive. These unusual cells were viewed and photographed in the late 1960s. Then the phenomenon of autophagy was not recognized as such. Some sort of mmor cell dormancy was considered (Sinkovics JG J Med edited by Julian Ambrus Sr 1970 1 15-25 313-326 reproduced in Sinkovics JG Cytolytic Immune Lymphocytes... Schenk Buchverlag, Passau/Budapest, 2008) (147).

Scwald X, Gcbcrt- gl B, Prassl S et aL integrin subunit CD 18 Is the T-lymphocyte receptor for the hclicobacter pylori vacuolating cytotoxin. Cell Host Microbe 2008 3(l) 20-29. 

Gebcrt B, Fischer W, iss E et al. Helicobacter pylori vacuolating cytotoxin inhibits T-lymphocyte activation. Science 2003 301(5636) 1099-1102. 

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