Distinct histological features characterize primary angiosarcoma of bone

Verbeke S L J, Bertoni F, Bacchini P, Sciot R, Fletcher C D M, Kroon H M, Hogendoorn P C W & Bovée J V M G
(2011) Histopathology  58, 254–264
Distinct histological features characterize primary angiosarcoma of bone Aims: To define the histological criteria of primary angiosarcoma of bone. Methods and results: Forty‐two angiosarcomas of bone in 23 males and 15 females were studied. Histological criteria were related to patients’ outcome. Eleven patients had multifocal lesions. Lesions were located in the long and short tubular bones followed by the pelvis, spine and trunk. Tumour cells were positive for CD31 in 38 of 40, von Willebrand Factor in 21 of 35, CD34 in 15 of 38, smooth muscle actin in 22 of 36, D2–40 in 11 of 35 and keratinAE1AE3 in 27 of 39. Thirty‐nine tumours showed an epithelioid phenotype. One‐ and 5‐year survival rates were 55% and 33%, respectively. Survival analysis showed that a macronucleolus, three or more mitoses per 10 high‐power field (HPF) and fewer than five eosinophilic granulocytes per 10 HPF within a tumour was associated with an even worse survival compared to the overall group. Conclusions: Because keratin positivity is seen in the majority of cases, pathologists should avoid misinterpretation as metastatic carcinoma. A macronucleolus, three or more mitoses per 10 HPF and fewer than five eosinophilic granulocytes per 10 HPF can be used to further define angiosarcoma of bone.     

Stress augments food 'wanting' and energy intake in visceral overweight subjects in the absence of hunger

Stress may induce eating in the absence of hunger, possibly involving changes in food reward, i.e. ‘liking’ and ‘wanting’. The objective of this study was to assess the effects of acute psychological stress on food reward, and on energy intake, in visceral overweight (VO) vs. normal weight (NW) subjects. Subjects (27 NW, age = 26 ± 9 yrs, BMI = 22 ± 2 kg/m²; 15 VO, age = 36 ± 12 yrs, BMI = 28 ± 1 kg/m²) came to the university twice, fasted, for either a rest or stress condition (randomized cross-over design). Per test-session ‘liking’ and ‘wanting’ for 72 items divided in six categories (bread, filling, drinks, dessert, snacks, and stationery (control)) were measured twice, each time followed by a wanted meal. Appetite profile (visual analogue scales, VAS), heart rate, mood state and level of anxiety (POMS/STAI questionnaires) were measured.High hunger and low satiety (64 ± 19, 22 ± 20 mmVAS) confirmed the fasted state. Elevated heart rate, anger and confusion scores (p ≤ 0.03) confirmed the stress vs. rest condition. Consumption of the first meal decreased hunger, increased satiety, and decreased ranking of ‘liking’ of bread vs. increased ranking of ‘liking’ of the control (p < 0.001). ‘Wanting’ for dessert and snacks, energy intake, carbohydrate and fat intake for the second meal stress vs. rest relatively increased in VO vs. decreased in NW (p < 0.02). During stress vs. rest VO showed a 6 ± 9% increase in percentage of daily energy requirements consumed over the two meals (p = 0.01).To conclude, visceral overweight subjects showed stress-induced food intake in the absence of hunger, resulting in an increased energy intake.     

Immunoassay of lymphocyte subsets in ovine palatine tonsils

By means of immunohistochemistry (IHC) and triple color flow cytometry (FCM), five commercial antibodies (anti-CD2, CD4, CD8, CD21, and CD45) were evaluated to quantify and localize the B- and T-lymphocytes in the ovine palatine tonsil. The results of both techniques were compared and evaluated. For the immunohistochemical analysis, three fixation methods were evaluated for their suitability to localize the different lymphocyte populations: 3.5% formaldehyde, zinc salts-based fixative and cryopreservation. The anti-CD45 antibody showed a positive reaction after all three fixation methods. The four other antibodies tested (anti-CD2, CD4, CD8 and CD21) were compatible with zinc salts-based fixation and cryopreservation. The CD21+ B-lymphocytes were localized in the tonsillar lymphoid follicles, while the CD2+ T-lymphocytes were abundant in the interfollicular regions and rare within the lymphoid follicles. The CD8+ T-cells were concentrated adjacent to the follicles, while the CD4+ T-cells were localized in the interfollicular zones as well as in the follicles. Both by immunohistochemistry and flow cytometry, a quantification of the different lymphocyte subsets was made. When comparing the results, a reversed B/T cell ratio was noticed. Possible explanations for this observation are discussed.     

Familial Crohn's disease in Belgium: pedigrees, temporal relationships among cases, and family histories

BACKGROUND: Recently we published an analysis of environmental factors in familial Crohn's disease (CD) in Belgium. The aim of the current study was to assess pedigrees and sibships, temporal relationships among cases, and family circumstances relevant to the frequency or onset of CD. STUDY: Twenty-one families with 3 or more affected first-degree relatives were studied. Seventy-four patients with CD and 84 unaffected family members were interviewed together at the parental home, with the aid of a 176 item questionnaire. Pedigrees were constructed establishing which family members had the disease and their relationships within sibships. Dates of onset of disease, validation of first symptoms and circumstances potentially relevant to the onset and distribution of disease within families were among the data documented during the interviews. Sequence of disease within families, consecutive versus nonconsecutive sequence of disease within sibships, and temporal relationships among cases were tabulated. RESULTS: In 12 of the 21 families CD occurred in a parent before CD in any children. Five affected fathers preceded 9 affected children; 7 affected mothers preceded 10 affected children. First borns were affected more frequently. Within sibships there were 21 instances (36%) when an affected sibling was consecutive in birth order with an affected sibling. When a parent had CD before the birth of the first child the "exposure interval" to CD in the children was longer (mean 22.4 y) than when the parent developed CD after the child was born (mean 11.8 y). CONCLUSIONS: The clusterings of CD within sibships and in time suggest that there is a contagious element in the etiology of CD.     

Synthesis and evaluation of a (99m)Tc-MAMA-propyl-thymidine complex as a potential probe for in vivo visualization of tumor cell proliferation with SPECT

INTRODUCTION: Cytosolic thymidine kinase (TK1) catalyzes phosphorylation of thymidine to its monophosphate. TK1 activity is closely related with DNA synthesis, and thymidine analogs derivatized with bulky carboranylalkyl groups at the N-3 position were reported to be good substrates for TK1. Accordingly, we have synthesized (99m)Tc-MAMA-propyl-thymidine and evaluated it as a potential tumor tracer. METHODS: The bis(S-trityl)-protected MAMA-propyl-thymidine precursor (3-N-[S-trityl-2-mercaptoethyl]-N-[N'-(S-trityl-2-mercaptoethyl)amidoacetyl]-aminopropyl-thymidine) was prepared in three steps, and its structure was confirmed with (1)H NMR and mass spectrometry. Deprotection of the thiols and labeling with (99m)Tc were done in a two-step, one-pot procedure, yielding (99m)Tc-MAMA-propyl-thymidine, which was analyzed with high-performance liquid chromatography, radio-LC-MS analysis (ESI+) and electrophoresis, and its log P was determined. The biodistribution in normal mice was evaluated, and its biodistribution in a radiation-induced fibrosarcoma (RIF) tumor mouse was compared with that of 3'-deoxy-3'-[(18)F] fluorothymidine [(18)F]FLT. RESULTS: (99m)Tc-MAMA-propyl-thymidine was obtained with a radiochemical yield of 70%. Electrophoresis indicated that the complex is uncharged, and its log P was 1.0. The molecular ion mass of the Tc complex was 589 Da, which is compatible with the hypothesized N(2)S(2)-oxotechnetium structure. Tissue distribution showed fast clearance from plasma primarily by the hepatobiliary pathway. Whole-body planar imaging after injection of (99m)Tc-MAMA-propyl-thymidine in an RIF tumor-bearing mouse showed high uptake in the liver and the intestines. No uptake was observed in the tumor, in contrast to the clear uptake observed for [(18)F] FLT visualized with muPET. CONCLUSIONS: Although it has been reported that TK1 accepts large substituents at the N-3 position of the thymine ring, the results of this study show that (99m)Tc-MAMA-propyl-thymidine cannot be used as a single photon emission computed tomography tumor tracer, probably because the (99m)Tc-MAMA ligand is too bulky to be tolerated by TK1.     

Hyperactivity of the HPA axis is related to dietary restraint in normal weight women

The objective of our study was to investigate the relationship between hypothalamus/pituitary/adrenal (HPA) axis functioning and dietary restraint in normal weight (BMI between 20 and 25 kg/m²) men and women. We therefore assessed in 38 men and 38 women HPA axis functioning, through measuring 5-hour cortisol exposure and cortisol feedback functioning through a dexamethasone (4 mg) suppression test. Eating behavior was assessed through the Three Factor Eating Questionnaire and body composition through hydro densitometry and deuterium dilution method. No relationship between HPA axis functioning and dietary restraint was found in men. Normal weight women with a restraint score ≥ 9 showed increased cortisol concentrations over a 5-hour time period, increased cortisol concentrations after a dexamethasone (4 mg) suppression test, higher BMI, and higher body fat percentage, when compared to women with a restraint score < 9. Moreover, a positive relationship was found between cortisol concentrations over a 5-hour time period and dietary restraint in combination with the disinhibition score (R² = 0.23, p < 0.001). We conclude that in normal weight women hyperactivity of the HPA-axis is related to dietary restraint especially in combination with disinhibition.     

Influence of dietary supplementation with Lactobacillus reuteri on the oral flora of healthy subjects

Investigate the presence of Lactobacillus reuteri in saliva after supplementation with L. reuteri and the probiotic effect of L. reuteri on plaque index and supra- and subgingival microbiota. MATERIAL AND METHODS: The study included 23 healthy individuals, randomised into test or control subjects. At baseline and after 12 weeks saliva samples, plaque index and supra- and subgingival plaque samples were obtained. The test subjects were given the study product (containing L. reuteri, ATCC 55730 and ATCC PTA 5289) and the control subjects placebo for 12 weeks. Microbiological analyses were done by checkerboard DNA-DNA hybridization technique and selective culturing for lactobacilli determination. RESULTS: A significant increase in total Lactobacillus counts in saliva occurred in both groups (p < 0.05) with a significant increase of L. reuteri (p = 0.008) in the test group.Termination of intervention resulted in a wash out of L. reuteri. The control group demonstrated a statistically significant increase in PII after 12 weeks (p = 0.023) whilst there was no significant change in the test group. A significant increase was found for most bacterial species in both groups in supra- and subgingival plaque with no significant difference for any of the species between the groups. The ratio between "bad/good" supragingival bacteria decreased for the test group but this decrease did not reach significance. The corresponding ratio for subgingival bacteria decreased significantly in both groups. Supplementation of L. reuteri resulted in presence of L. reuteri in saliva but L. reuteri was washed out after termination of intervention. No significant effect on supra- or subgingival microbiota was observed. The significant increase in PII in the control group with no significant change in the test group may, however, indicate a probiotic effect of L. reuteri in this study population.