O. Haferkamp

Gastritis, Intestinal Metaplasia and Dysplasia Versus.Benign Ulcer in Stomach and Duodenum and Gastric Carcinoma -A Histotopographical Study

In histological examination of gastrectomy specimens from patients with duodenal ulcer, gastric ulcer, and early and advanced cancer, both chronic atrophic gastritis and intestinal metaplasia were identified in 54% of the cases with duodenal ulcer. At 90 to 100%, respectively, these mucosal changes were approximately twice as frequent with gastric ulcer and early and advanced gastric cancer. Mild dysplasia occurred in 54% of the cases with duodenal ulcer; occurred somewhat more frequently with gastric ulcer, in 75% of the cases; and in almost all cases with early and advanced gastric cancer, at 90% and 100%, respectively. Whereas 27% of the cases with duodenal ulcer, 62% with gastric ulcer, and 90% and 95% of the respective cases with early and advanced gastric cancer showed moderate dysplasia, only severe dysplasia in early gastric cancer (40%) and advanced gastric (81%) was clearly more frequent in comparison to duodenal ulcer (9%) and gastric ulcer (12%). In the cases with duodenal ulcer chronic atrophic gastritis and intestinal metaplasia were limited mostly to the antrum; with gastric ulcer and cancerous stomach disorders, they also occurred in other stomach sections. Mild and moderate dysplasia conformed to the same distribution pattern. Severe dysplasia, which was only detected in two ulcer cases, was not only substantially more frequent in cases with early and advanced gastric cancer, but also showed a clear topographic relationship to cancer localization in the stomach.

Statistical analysis of intramembranous particles using freeze fracture specimens

We studied the point processes of intramembranous particles of mitochondrial membranes from HeLa cells using the freeze fracture technique. Three groups – under normal conditions, after exposition with rotenone, and after exposition with sodium acid – were compared. First, we used several summary statistics in order to study the two‐dimensional point patterns of intramembranous particles within each group. Then, we compared the patterns in different groups by bootstrap tests using the K‐function and the nearest neighbour distance function G(r). Estimation of the G‐function provided significant results but no significant differences between groups were found using the classical K‐function; estimation of G(r) should therefore not be omitted when studying observed planar point patterns.

Pathomorphology of humoral, cellular and combined primary immunodeficiencies.

Histologic, immunohistologic and electron microscopic findings in three children with primary immunodeficiencies are reported. Classical X-linked infantile agammaglobulinemia Bruton was present in case 1 (♂, aged 16 years), selective cellular immunodeficiency with thrombopenia in case 2 (♂, aged 2 1/2 years) and non-lymphopenic severe combined immunodeficiency in case 3 (♂, aged 1 3/4 years). At autopsy, all three cases exhibited unusual types of pneumonia. In case 2 a generalized cytomegalovirus infection was present. Case 3 disclosed panmyelopathia and chronic liver lesions due to severe GvH-reaction subsequent to bone marrow transplantation. A detailed morphologic study of the immune system revealed distinct alterations in the thymus, spleen, and lymph nodes and the lymphatic tissues of the gastrointestinal tract characteristic of an immunodeficiency state, either humoral (case 1), cellular (case 2) or combined (case 3).

Transformation of C18-, C19- and C21-steroids by cultures of Candida albicans.

Abstract Proliferating cultures of Candida albicans were found to contain constitutive 3α-, 3β-, 17β-, 20α- and 20β-hydroxysteroid dehydrogenase activities and to lack steroid hydroxylases and 4-ene-hydrogenases. Ring -A/B-trans configurated steroid (5α-dihydrotestosterone) was the preferred substrate for 3β-reduction. whereas no substrate preference for 3α-reduction was found. The ratio of the two 20-epimeric C21-steroid alcohols formed by 20-reduction was dependent on the substrates structure. Introduction of a 17α-hydroxy group strongly enhanced 20α-reduction whereas an additional 21-hydroxy group decreased 20α-, but increased 20β-reduction. An additional 11-oxo function only weakly decreased both 20β- and 20α-reduction, whereas an 11β-hydroxy group caused a very substantial decrease.

The effects of nickel ions on articular chondrocyte growth in monolayer culture

SummaryMonolayer cultures of lapine articular chondrocytes were used to study the effects of nickel ions (Ni++) on chondrocyte proliferative capacity, proteoglycan synthesis and cellular morphology. Nickel depressed chondrocyte proliferation at the highest concentration tested (100µmol/l;P<0.01) and also exerted a dose-dependent inhibition of proteoglycan synthesis (50 and 100µmol/l;P<0.01). Despite both these effects, no evidence of chondrocyte damage was detectable at the light-microscopical level. The possible significance of the nickel-induced reduction of articular chondrocyte proteoglycan synthesis for the functional integrity of the residual cartilage following hemiarthroplasty operations is discussed.

Pathomorphologic Findings in Severe Combined Immunodeficiency and Reticular Dysgenesia

Pathomorphologic findings in an 11 month old boy with severe combined immunodeficiency (case 1) and in a 4 month old boy with reticular dysgenesia (case 2) are reported. Case 1: The bone marrow exhibited regular granule-, erythro- and thrombopoiesis. The hypoplastic thymus consisted exclusively of epithelial reticulum cells. The spleen and lymph nodes showed considerable depletion of lymphocytes in both the T- and B-cell areas. There was a complete lack of all lymphatic structures in the gastrointestinal tract and aplasia of the tonsils. Death resulted from Candida sepsis in conjunction with giant cell pneumonia closely resembling Hechts pneumonia in measles. Case 2: The bone marrow showed a total lack of granulopoiesis. The strongly dysplastic thymus weighed only 1 g. The spleen, the lymph nodes and the gastrointestinal tract exhibited a very strange histologie structure resulting from a complete absence of lymphocytes and plasma cells. The tonsils were aplastic, the parathyroid glands as well as the other endocrine glands were normally developed. The cause of death was Klebsiella sepsis and Pneumocystis pneumonia, the latter without the characteristic interstitial plasma cell infiltration. The importance of the immune system for activation of the nonspecific mechanisms of defense is discussed with respect to the two types of immunodeficiency states described here.

The effect of soluble sodium urate on the proliferation and proteoglycan synthesis of lapine articular chondrocytes in monolayer culture

SummaryThe effects of soluble monosodium urate (350, 50, and 5 μmol/l) on the proliferation and proteoglycan synthesis of lapine articular chondrocytes were studied in a monolayer culture system. Cellular proliferation in vitro was unaffected by urate treatment. Chondrocytes treated with 50 μmol/l sodium urate showed a 26% reduction in binding of 35SO4 to matrix macromolecules. However, this reduction did not achieve statistical significance. The 350 and 5 μmol/l concentrations did not alter 35SO4 binding. It is proposed that monosodium urate has no marked direct effect on chondrocyte viability, proliferation and proteoglycan synthesis.

Lipid storage in cultured articular chondrocytes due to prostanoid precursors and a prostanoid synthesis inhibitor

SummaryLapine articular chondrocytes were subcultured in the presence or absence of the prostanoid precursors, arachidonic acid or dihomo-gammalinolenic acid, and the cyclooxygenase inhibitor indomethacin. Lipid storage was studied microscopically using the Sudan black staining method. Control chondrocyte cultures showed a weakly positive staining reaction until confluence was reached, at which point the intra-cytoplasmic lipid content decreased. Both arachidonic acid and dihomo-gamma-linolenic acid at 100 μmol/l caused a marked increase in lipid storage which continued even after confluence was achieved. 1 μmol/l concentrations were indistinguishable from controls, whereas 10 μmol/l concentrations elicited a slight increase in lipid storage compared with controls. The prostaglandin cyclooxygenase inhibitor indomethacin did not affect chondrocyte lipid storage. However, administration of a prostanoid precursor in the presence of indomethacin caused a massive increase in intra-cytoplasmic storage of lipid, eventually leading to cell death. A possible explanation is that indomethacin may alter chondrocyte lipid metabolism in the presence of substrate molecules by rechanneling lipid synthesis away from the prostaglandin pathway to other lipid synthetic pathways.

Mitochondrial complex I and III mutations and neutral-lipid storage in activated mononuclear macrophages and neutrophils: A case presenting with necrotizing myopathy, poikiloderma atrophicans vasculare, and xanthogranulomatous bursitis

We report the case of a 57-year-old woman suffering from xanthogranulomatous bursitis, necrotizing myopathy, and poikiloderma atrophicans vasculare, which are associated with marked accumulation of neutral-lipid storage phagocytes. The observed lipid storage was restricted to activated phagocytes independent of the presence of tissue necrosis and was not seen either in circulating blood leukocytes or in muscle fibers. The patients daughter disclosed xanthomatous inflammatory reaction with profound delay of wound healing secondary to pelviscopy. Examination of the mitochondrial DNAs of the patient, her daughter, and her two grandchildren revealed two homoplasmic mutations at positions 13708 and 15257 of the mitochondrial genome. We discuss the involvement of these mutations in the pathogenesis of xanthomatous and xanthogranulomatous inflammation. Further investigations are required to test whether impairment of aerobic energy production independent from mitochondrial DNA mutations (eg, by hypoxia or microbial toxins) similarly can cause the accumulation of lipid-laden macrophages and explain the persistency of xanthogranulomatous inflammation.

Relationships between lymphocyte cholesterol homeostasis and LDL-cholesterol.

The homeostasis of cholesterol was studied in lymphocytes freshly isolated from the blood and cultured with or without low-density lipoprotein (LDL). The content of cholesterol decreased in the lymphocytes cultured without LDL, whereas LDL substituted for cellular cholesterol losses, in spite of almost suppressed LDL-receptor and lymphocyte cholesterol synthesis. Free cholesterol was taken up from LDL mainly via cholesterol exchange and, in contrast to esterified cellular cholesterol, rapidly excreted into the medium. In vitro stimulation of lymphocyte cholesterol synthesis was correlated to the ratio of esterified to free LDL-cholesterol in the blood from which the lymphocytes had been isolated. This result probably reflects the different rates of influx and efflux of esterified or free cholesterol between plasma lipoproteins and lymphocytes. These effects should be taken into account if LDL-cholesterol is determined in plasma for the evaluation of an individuals atherosclerotic risk.