David B. Jones

Malignant lymphoma of true histiocytic (monocyte/macrophage) origin

Since the advent of the newer classifications of non‐Hodgkins lymphoma and the realization that the majority of tumors classified as histiocytic under the Rappaport classification were in fact of lymphocytic origin, there have been remarkably few reports of true histiocytic (monocyte/macrophage) tumors and it has been suggested by some that such tumors should not be considered as a variety of malignant lymphoma. This article describes five patients with malignant lymphoma of neither B‐ or T‐lymphocyte origin in whom the malignant cells could be characterised immunologically, cytochemically, and immunohistochemically as of true histiocytic derivation. The cases showed considerable morphologic diversity but there were shared characteristics at both light microscopic and ultrastructural levels. Positive immunohistochemical staining for α1‐antitrypsin was the single most useful criterion in classifying these tumors. Without the use of special techniques there were no clinical or pathologic features that reliably distinguished these cases from non‐Hodgkins lymphomas of lymphocytic derivation. Tumors of histiocytic origin are, therefore, inevitably being included among the non‐Hodgkins lymphomas and are most appropriately classified as such. Identification of histiocytic lymphomas should be encouraged so prognosis and optimum treatment can be established.

The interaction of vitamin A deficiency and rotavirus infection in the mouse

Weanling mice were fed on a control diet ad lib., a vitamin A-deficient diet ad lib. or pair-fed to the intake of the vitamin A-deficient group. Vitamin A deficiency was induced by 63-70 d of age. On day 77 mice were given 30 microliters rotavirus/mouse orally and examined histologically 1 week later. There were no changes in relative liver weight in any of the groups, but following infection animals deficient in vitamin A showed a significant increase in spleen weight compared with the other groups. The relative weight of the thymus was reduced by vitamin A deficiency, in both non-infected and infected animals. The histology of the spleen, thymus and small intestine was similar in all three dietary groups before infection. The number of goblet cells per duodenal villus in vitamin A-deficient animals was significantly lower than that of control and pair-fed animals. In the small intestine of vitamin A-deficient animals, rotavirus infection caused dramatic changes to the mucosa, with almost complete destruction of the tips of the villi, but control and pair-fed animals had normal villi. It is concluded that although rotavirus infection and vitamin A-deficiency cause few changes alone, in their action together there is significant destruction of the mucosal barrier of the small intestine.

Effect of vitamin A deficiency on the immune response to epizootic diarrhoea of infant mice (EDIM) rotavirus infection in mice.

The effect of vitamin A deficiency on the immune response to epizootic diarrhoea of infant mice (EDIM) rotavirus was studied in mice. The virus was given by oral dosing or by intraperitoneal injection. For oral challenge, weanling mice were fed on either a control or vitamin A-deficient diet ad lib. or pair-fed the control diet to the intake of the vitamin A-deficient group. A fourth group was fed on the vitamin A-deficient diet ad lib. for 10 weeks and then refed the control diet for 2 weeks. On day 77, mice were each given 30 microliters EDIM rotavirus orally and the animals were killed and examined 1 week later. The delayed-type hypersensitivity (DTH) response to picryl chloride was measured as an index of cell-mediated immunity. For intraperitoneal challenge, weanling mice were fed on either the control diet or the vitamin A-deficient diet ad lib. or pair-fed the control diet to the intake of the vitamin A-deficient group. On day 77, mice were each injected intraperitoneally with 30 microliters EDIM rotavirus and 1 week later antibody production was measured. In both experiments the body-weight, liver and serum vitamin A levels of the vitamin A-deficient group were significantly lower than the control or pair-fed groups. Following oral dosing the serum antibody levels specific to rotavirus were statistically significantly lower in vitamin A-deficient animals than the control or pair-fed groups. Vitamin A-deficient mice also showed an impaired DTH response compared with the control and pair-fed animals. Animals refed vitamin A for a short period showed a partial restoration of the antibody response. Following intraperitoneal challenge no statistically significant changes were observed in the serum antibody levels between any of the dietary groups. It is concluded that vitamin A deficiency impaired antibody production when rotavirus was given orally. Vitamin A deficiency also impaired cell-mediated immunity.

Morphological evidence for calcium-dependent association of calgranulin with the epidermal cytoskeleton in inflammatory dermatoses

The association of calgranulins. intracellular calcium‐binding proteins, with the keratinocyte cytoskeleton has been studied. These molecules are expressed in various inflammatory dermatoses and in organ‐culture explants. Triton X‐100 extraction in the presence of calcium or EDTA suggested that calgranulins are detergent insoluble in the presence of calcium. The molecules were localized in a plaque‐like structure at the cell periphery in lesional skin and in organ‐culture explants. Following induction of calgranulins in vitro there was a redistribution of the intermediate filament cytoskeleton into a perinuclear halo, although desmosomes remained intact. These various features suggest that these members of the S‐100 protein family have a role in cytoskeletal changes seen in various skin diseases.

Paget's disease of the nipple. Immunohistochemical localization of milk fat globule membrane antigens

The authors have used the indirect immunoperoxidase technique to examine the presence and distribution of milk fat globule membrane antigens in 12 cases of mammary Pagets disease using two monoclonal antibodies, HMFG‐1 and HMFG‐2. These stain breast epithelial cells but do not stain normal epidermis. The Pagets cells showed a similar pattern of cytoplasmic staining to that seen in the underlying intraduct or invasive carcinoma, therefore confirming them to be malignant ductal cells. To support this one of the cases was stained with the antibody LE 61 which is specific for nonepidermal epithelial cytokeratins. The result was strongly positive in Pagets cells in the epidermis but not in squamous cells.

Effect of undernutrition on the immune response to rotavirus infection in mice.

The effect of moderate and severe undernutrition on the immune response to EDIM rotavirus was studied in mice. A moderate state of undernutrition was produced by feeding weanling mice either 15 or 30% less diet than the control group had eaten on the previous day, for 7 weeks. After 6 weeks, mice were given 30 microliters/mouse of EDIM rotavirus orally and the antibody production was measured 1 week later. The delayed-type hypersensitivity (DTH) response to picryl chloride (PC) was measured as an index of cell-mediated immunity. For severe undernutrition, weanling mice were fed either 30 or 50% less diet than the control group had eaten on the previous day, for 12 weeks. After 11 weeks of feeding, animals were given 30 microliters/mouse of EDIM rotavirus either orally or intramuscularly and the antibody production was measured 1 week later. In moderate undernutrition, the serum antibody levels specific to rotavirus and the DTH response to PC were normal in all dietary groups compared with the control group. In severe undernutrition, the antibody levels following oral challenge of rotavirus were similar in all dietary groups. There was a significant impairment of serum antibody levels following intramuscular challenge in the group fed 50% less than the control group. It is concluded (1) that a balanced reduction in food intake does not impair the immune response, unless severe restriction is maintained for a long period of time, and (2) that the antibody response varies with the route of immunization.

Genotypic Heterogeneity of Node Based Peripheral T-cell Lymphoma

PTCL represents a diverse group of histological entities that defy classification schemes based on normal T cell differentiation, differ in their clinical presentation and behave unpredictably. Genetic analyses of this phenotypically heterogeneous group have clearly shown that histologically defined PTCL may be subdivided on the basis of clonal gene rearrangements. The absence of clonal gene rearrangements in a significant proportion of PTCL cases has increased the complexity of classification. The data presented in this review suggest that a molecular classification would allow true reflection of PTCL aetiology, but carefully coordinated studies are required to evaluate the clinical usefulness of such a classification scheme.

Effect of severe food restriction on the gut following rotavirus infection in mice

The effect of severe food restriction on the histopathology of the gut following infection with epizootic diarrhoea of infant mice (EDIM) rotavirus was studied in mice. Over a period of 12 weeks, weanling mice were fed either 70 or 50% of the diet eaten by a control group on the previous day. After 11 weeks of feeding, animals were given 30 microliters/mouse of EDIM rotavirus orally and the histopathology of the gut and lymphoid organs examined. The histology of the spleen and thymus of different dietary groups appeared normal and no changes were observed due to the rotavirus challenge. Both the control and 70% food group had normal villi in the small intestine. In contrast there was severe atrophy of the villi in the animals whose intake was reduced by 50%. No additional damage to the villi was seen in association with the rotavirus infection. It is concluded that a prolonged, balanced reduction in food intake can itself cause villous atrophy in the gut but following rotavirus infection, adult animals were able to resist further villous damage.