Macrophages in human tumours: An immunohistochemical study

Forty-five human malignant tumours and three benign lesions were stained histochemically for non-specific esterase (NSE) and acid phosphatase (AP), and immunohistochemically for lysozyme. Most of the tumours contained small numbers of lysozyme positive macrophages (LPM), but colonic tumours showed moderate numbers of LPM around the edge of the lesions. Gastric and secondary duodenal tumours (n = 3) contained moderate numbers of intralesional LPM in addition. Most squamous and all mesenchymal tumours contained no lysozyme positive macrophages. The usefulness of the three staining methods was assessed and it was concluded that lysozyme was specific but detected only part of the macrophage population. Neutrophil polymorphs were also stained but could be recognised by nuclear morphology. AP and NSE detected more cells but stained tumour cells as well as macrophages, making these methods of limited use in tumours showing invasion of the stroma by single cells or small groups of cells.     

Pulmonary oedema in rats given dehydromonocrotaline: a topographic and electron-microscope study.

Study of cleared, histological and electron-microscope specimens shows that increased vascular permeability plays a major role in the formation of the pulmonary oedema and pleural effusions that occur in rats following the intravenous injection of a large dose of dehydromonocrotaline. There is a latent interval of 6-8 hr between injection of the dehydroalkaloid and the start of increased permeability which appears to be due to a direct damaging effect of the toxin on the endothelium of pulmonary capillaries and small venules. The endothelial injury does not cause permanent disruption of small blood vessels, and 2 days after injury all vessels are patent and lined by a complete layer of endothelium. Large numbers of mononuclear cells are present in the interstitial tissues of the lung 44 hr after injury. These cells appear to be emigrated blood monocytes but the cause of their emigration and their role in the subsequent progression of this type of injury to the lung are not clear.     

Hepatic tumours induced by anabolic steroids in an athlete.

A fatal rupture of an hepatic tumour occurred in an athlete who had been taking anabolic steroids for several years as an aid to body building. The case illustrates the hazards of non-therapeutic androgen administration, and emphasises the need for athletes to be made clear of the disturbances to gonadal function, liver structure and function, and the threat to life.     

Late-onset cerebellar degeneration in mice induced transplacentally by methylnitrosourea

A late-onset degenerative disease in the cerebellum was produced in the offspring of mice exposed to 1 mg/kg of the direct-acting DNA alkylating agent methylnitrosourea (MNU) on day 16 of gestation. This intrauterine exposure to MNU also provoked a progressive retinal degeneration that was described elsewhere. Mild ataxia in the MNU-exposed animals was expressed by 20 weeks of age. Although animals appeared normal in the immediate post-natal period, quantitative histological evaluation of cerebellar coronal sections indicated that MNU-exposed animals had a significantly greater number of pyknotic Purkinje cells than age-matched controls. The number of pyknotic Purkinje cells declined with age in the drug exposed animals; however, the percentage of pyknotic Purkinje cells to total number of Purkinje cells still was greater in MNU-induced animals at 36 weeks than in controls, suggesting that a slow degenerative process was ongoing in the MNU-exposed animals. Furthermore, the folia were grossly disrupted in 90% of the older MNU-exposed animals (ages greater than 12 weeks), suggesting permanent cerebellar disruption macroscopically. Such intrauterine exposure to low doses of alkylating agents may be potentially useful in modeling degenerative neuronal diseases.     

Perivascular pseudorosettes in childhood brain tumours: an ultrastructural and immunohistochemical study

Perivascular pseudorosettes (PP) in childhood central nervous system tumours were examined with light and electron microscopy and immunohistochemistry for glial fibrillary acidic protein, S-100 protein and albumin. One kind of PP at light microscopy comprised a central thin-walled vessel surrounded by a thick mantle of eosinophilic fibrillary material and rings of usually regular nuclei. Adjacent tumour tissue was compact. This type was correlated closely with ultrastructural evidence of ependymal differentiation. The central vessel showed continuous endothelium in all. Another type of PP comprised a central vessel of varying thickness surrounded by hyaline material, clearly defined tapering processes, and rings of often irregular nuclei. Adjacent tissue showed extensive edema and microcystic change. Ultrastructurally, this type showed no ependymal differentiation except in one myxopapillary ependymoma. Fenestrated vessels were seen in half of the tumours associated with this kind of PP. It is proposed that variation in vascular permeability, rather than in the structure of tumour cells, is the main cause for the difference in histological appearance of the two types of PP. Fenestrated vessels may also be responsible for the "myxoid" change in myxopapillary ependymomas. The amount of extracellular albumin showed no consistent correlation with the presence of fenestrations in vessels. A variable degree of positivity to GFAP and S-100 protein was seen in the tumours associated with both types of PPs with no clear difference in pattern.     

DNA ploidy distribution in renal tumours induced in male rats by dietary ochratoxin A.

DNA ploidy distribution, measured in experimental renal tumours that occurred in twelve ageing male Fischer rats derived from carcinogenicity experiments on ochratoxin A (OTA) in response to chronic dietary exposure, was diploid in all renal adenomas and aneuploid in all carcinomas, correlating with their typical organised and disorganised histopathology, respectively. Aneuploidy was also detected in renal tissue in which karyomegaly, induced by OTA, was analogous to that caused by the fungus Penicillium polonicum. Thus, the experimental rat renal carcinoma could arise within an adenoma directly from certain persistent karyomegalic tubular epithelial cells long after their particular genetic damage has been caused during a protracted period of OTA insult.     

Macrophages are essential for antitumour effects against weakly immunogenic murine tumours induced by class B CpG-oligodeoxynucleotides

We explored the mechanisms of class B CpG-oligodeoxynucleotide-induced antitumour effects against weakly immunogenic tumours. Treatment with CpG-oligodeoxynucleotide 1826 (CpG) induced similar antitumour effects in B16 melanoma-bearing immunocompetent C57BL/6 mice and T-cell-deficient severe combined immunodeficient (SCID) mice, and NXS2 neuroblastoma-bearing T-cell-depleted A/J mice. Both macrophages (Mphi) and natural killer (NK) cells from CpG-treated C57BL/6 mice could mediate cytotoxicity in vitro, suggesting that these cell types might control tumour growth in vivo. However, CpG treatment of SCID/beige mice or T-cell-depleted and NK-cell-depleted A/J mice still induced antitumour effects in vivo, arguing against a major role of NK cells in the antitumour effects of CpG in the absence of T cells. In contrast, CpG treatment of interferon-gamma knockout (IFN-gamma(-/-)) C57BL/6 mice resulted in no antitumour effects in vivo and no Mphi-mediated tumoristasis in vitro despite unaltered cytolytic function of NK cells in vitro. Moreover, Mphi inactivation by silica substantially reduced CpG-induced suppression of tumour growth in vivo, revealing an important role of Mphi in CpG-induced antitumour effects. The in vitro tumouritoxicity by CpG-stimulated Mphi (CpG-Mphi) correlated with tumour cell mitochondria dysfunction and involved nitric oxide (NO), tumour necrosis factor-alpha (TNF-alpha) and IFN-gamma, whereas interleukin-1alpha (IL-1alpha), IL-1beta, IFN-alpha, TNF-related apoptosis-inducing ligand and Fas ligand played insignificant roles in CpG-Mphi tumouritoxicity. Taken together, our results indicate that the growth control of weakly immunogenic tumours during CpG-immunotherapy is mediated predominantly by Mphi, rather than T cells or NK cells.     

DNA study of bladder papillary tumours chemically induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in Fisher rats

To examine DNA abnormalities in bladder papillary tumours induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in female rats, using image cytometric DNA analysis and cytogenetics. Thirty female rats were exposed to BBN in their drinking water for 20 weeks. One group of 10 animals served as controls. The animals exposed to BBN were killed at a rate of two per week, with the bladder being collected under aseptic conditions and those tumours with exophytic growth removed. The nuclear DNA content of the tumours was evaluated using image cytometric analysis. In two rats part of the tumour pieces was stipulated for culturing. Cytogenetic analysis was performed on at least 30 cells from each cell population and on both tumours. Papillary carcinomas were classified as low grade and high grade. DNA ploidy studies were carried out on 28 low-grade and 21 high-grade papillary carcinomas. Histograms obtained by image analysis showed that a normal urothelium was diploid; 28.6% and 100% of low-and high-grade papillary carcinomas were aneuploid respectively. Both tumours used for cell culture showed multiple numerical and structural chromosome alterations and several marker chromosomes. Image cytometric DNA analysis proved to be a good and reliable method for examining DNA alterations in papillary bladder carcinomas. The present findings establish that the DNA content is statistically different between low-grade and high-grade papillary carcinomas and that deviation from the diploid number is markedly higher in the high-grade ones. In addition, the occurrence of marker chromosomes seems to be related to the aggressiveness of the tumour.     

Morphological analysis of malignancy: a comparative study of transplanted brain tumours.

A comparative study of the cellular composition and ultrastructural features of rat brain tumours produced by early and late passage of neoplastic glial cells was carried out. The cells injected intracerebrally were of a clone neoplastic astrocytes (A15A5) derived from a mixed glioma induced transplacentally by N-ethyl-N-nitrosourea (ENU) in a BD-IX rat. The neoplastic cells were maintained for various lengths of time in vitro and then injected (5 X 10(5) cells) into the left frontal lobe of the brains of syngeneic rats, resulting in a 100% tumour yield. Gliomas produced by cells of earlier passages were less malignant and contained better differentiated astrocytes than those produced by cells of later passages. There were also differences in size, shape, extracellular space, presence of haemorrhage and necrosis, vascularity and invasion of the surrounding tissues. Thus the morphological features of transplanted tumours in vivo correlated well with the in vitro behaviour of neoplastic glial cells.