Brain tissue microarrays in dementia research: White matter microvascular pathology in Alzheimer's disease

Tissue microarrays (TMA) consist of up to 1000 cylindrical tissue cores from different donor paraffin blocks relocated into one recipient block, allowing for efficient histopathological studies by fluorescence in situ hybridization, RNA in situ hybridization or immunohistochemistry. On the background of the increasing interest of the TMA technique in cancer research and the suggestion of its application also in studies of non‐neoplastic intracranial disorders, the technique was applied to pathologic white matter in AD brains. Eight cases with AD and concomitant white matter pathology were neuropathologically diagnosed on whole brain coronal slides. The TMA technique was used to grade severity of white matter pathology and to quantify small vessels with traditional staining and immunohistochemical markers. These measurements were compared with the whole brain neuropathological assessment. The technique produced good results with preserved tissue structures as confirmed by the whole brain evaluation. Severity of white matter pathology evaluated on the TMA cores correlated negatively with small vessel quantities, and statistically significant differences in vessel quantities paralleled different grades of white matter pathology. It is concluded that the TMA technique could be further utilized in studies of dementing disorders, and may have its advantages in large, clinically well‐characterized materials (e.g. in quantitative mapping of white matter changes).     

Primary lymphocytes as predictors for species differences in cytotoxic drug sensitivity.

Several in vitro methods have been suggested to predict drug-induced haematotoxicity and species differences; the most commonly used being the clonogenic CFU-GM assay. The aim of the current study was to evaluate whether primary lymphocytes from peripheral blood, assayed with a short-term non-clonogenic assay, could be used to detect species differences in drug sensitivity, and offer an alternative to the CFU-GM assay. The effect of 17 different cytotoxic drugs on lymphocytes from human, dog, rat and mouse was evaluated. A higher sensitivity of human than mouse lymphocytes was seen for topotecan and for 3 of 5 antimetabolites tested. Clear species specificity was also seen for the proteasome inhibitor bortezomib where rodent cells were 50-300 times less sensitive than human cells. Good agreement between our data and published CFU-GM data was observed, suggesting that primary lymphocytes may be a useful model for species difference screening in drug development.     

Tension leads to increased neutrophil accumulation and decreased laparotomy wound strength

Wound margin strength was measured immediately after and at 72 hours after median laparotomy in rats. The laparotomy wound was sutured with or without tension, and wound margin strength was measured as breaking strength with the sutures in situ. In wounds sutured without tension, no decrease in breaking strength was observed at 72 hours; in rats sutured with tension, breaking strength decreased by 77%, and in almost half of the animals the sutures cut through. There was markedly increased accumulation of neutrophil leukocytes around the sutures in the tension group, as indicated by increased tissue myeloperoxidase activity. The decrease in breaking strength was abolished by treatment with an inhibitor of the collagen-degrading proteinases of the neutrophils (the soybean trypsin inhibitor). Although the decrease in breaking strength should be due to collagenolysis, there were no changes in collagen content or solubility around the sutures, indicating that the changes in collagen were too delicate to be revealed by the methods used. We conclude that the decrease in breaking strength was caused by the neutrophils.     

A tobacco quit and win model in the Stockholm cancer prevention programme.

The main objective of the Stockholm Cancer Prevention Programme (SCPP) is to reduce cancer incidence and mortality among the 1.6 million inhabitants in Stockholm county by reducing risk factors particularly related to lifestyle. The objective of the SCPP's tobacco action programme is to reduce the number of adult daily users of tobacco (including oral snuff) to 20% by the year 2000. In 1988, a nationwide Quit and Win contest was conceived as part of this long-term programme. The contest recruited nearly 13,000 participants or 0.6% of the daily tobacco users in Sweden over the age of 16 years. More than 60% of the participants were recruited from Stockholm county. This corresponds to 1.9% of the daily tobacco users in Stockholm county compared with 0.3% in the rest of Sweden. The pharmacies and the public health services organizations were the principal distributors of contest entry forms. Sixty-two percent of the men and 59% of the women were tobacco free one month after the contest, and after 6 months the corresponding figures were 30 and 25%, respectively.     

Liver metabolic effects of intestinal shock and naloxone treatment in the rat

The liver metabolic response of rats following a standardized intestinal shock, induced by applying a pressure of 120 cm water on the mesenteric vessels for 60 min, was studied. Immediately prior to the release of the pressure on the vessels saline or naloxone was given either as a single injection or as a continuous infusion. After the reperfusion of the intestine no early disturbances in liver metabolism were found as evidenced from the ATP, glucose and lactate levels in liver biopsies taken 15 min following reflow. Within 60 min of reflow reduction of ATP and increases of glucose and lactate levels occurred. There were no major hemodynamic or liver metabolic differences between saline- and naloxone-treated shocked rats. When saline or naloxone was given as a continuous infusion, the changes in liver metabolism were, however, less severe than those observed in the single injection situation pointing toward a non-specific effect of volume replacement rather than a blockade of opioid receptors. Hepatic hypoxia and/or cellular effects of "shock factors" could be mechanisms of pathophysiologic importance for the disturbed liver metabolism in this shock model.     

Tenascin-C in primary Merkel cell carcinoma

BACKGROUND/AIMS: Merkel cell carcinoma (MCC) is a rare malignant cutaneous neuroendocrine tumour that mostly affects the elderly. It shows rapid progression of the primary tumour, together with a vertical growth pattern into the underlying subcutaneous tissue. Metastatic dissemination to regional lymph nodes is early and frequent. Tenascin-C (Tn-C) is a large extracellular matrix glycoprotein that is expressed in various benign and malignant processes. Expression of Tn-C is also associated with invasion and cellular proliferation, and is often downregulated in fully evolved advanced carcinomas. In previous studies, Tn-C expression correlated with prognosis in tumours of different origin. METHODS: Immunohistochemistry was used to investigate the expression of Tn-C in 25 MCC specimens and to evaluate the prognostic importance of this glycoprotein. RESULTS: Seventeen samples expressed Tn-C. Staining was mainly seen in the invasion borders and within the connective tissue septae inside the tumours. The expression of Tn-C correlated significantly with large tumour size. There was also frequent expression of Tn-C in primary tumours with metastatic dissemination. Most of the Tn-C negative samples were of small size. CONCLUSIONS: Tn-C expression seems to increase with tumour size and malignant behaviour. Expression was slightly enhanced in tumours with high proliferative indices. Expression is seen mainly in areas of invasive growth and, in this respect, resembles that of other invasive tumours.     

P75 nerve growth factor receptor is expressed in regenerating human nerve grafts

BACKGROUND: The purpose of this study was to elucidate the expression of p75 nerve growth factor receptor (p75NGFR) in human cross-facial nerve grafts and to compare the immunohistological findings with patient data and the functional outcome in facial reanimation. MATERIALS AND METHODS: The study comprised 37 sural nerve graft specimens. All of the patients had long-lasting complete facial paralysis and were operated on by the standard two-stage procedure involving cross-facial nerve grafts and microneurovascular muscle transfer. Nerve biopsies were taken 4 to 20 months (mean, 8 months) after the cross-facial nerve grafting. Immunohistochemistry for p75NGFR as well as for Schwann cells (S-100; Dako, Glostrup, Denmark) and for Neurofilament-200 (NF-200; Boehringer, Mannheim, Germany) was performed. RESULTS: In graft biopsies, the mean number of NF-200-positive axons amounted to 38% (range, 6-81%) of that in control samples. Further, regenerated axons were thinner than in control samples. Morphologically, the grafted nerves were characterized by fibrosis and invasion of inflammatory cells. A longer time between cross-facial nerve grafting and biopsy sampling correlated with a higher number of viable axons (NF-200) (P = 0.002). In all cases, expression of p75NGF receptor was clearly higher at the distal end of the grafted nerve. Expression of p75NGFR was lower in older than in younger patients (P = 0.003). A high expression of p75NGFR was often seen with better function of the transplanted muscle. CONCLUSION: Increased expression of p75NGFR in human nerve grafts was noted, especially in younger patients. We suggest that p75NGFR expression might be a contributing factor in a successful axonal regeneration and eventual recovery of muscle function.     

Esophageal and jejunal motor function after total gastrectomy and Roux-Y esophagojejunostomy

Emptying and peristaltic activity of the esophagus and proximal jejunum were studied using scintigraphy and fluoroscopy documented on videotape in 11 patients after total gastrectomy and Roux-Y loop reconstruction. Impaired esophageal motor function, as judged by both methods, was seen in five patients who were all 50 years of age or older. This was in contrast to the findings in a group of healthy control subjects, all over 50 years of age, in whom esophageal function appeared normal on scintigraphy in five of seven. Disturbed jejunal function, as judged by radiography, was found in eight patients, whereas the emptying rate according to scintigraphy was judged normal in all but two patients. Five of the patients complained of various adverse alimentary tract symptoms, but the scintigraphic and radiographic findings did not correlate with these symptoms.