Raised tissue copper levels in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a well-recognised-potentially malignant condition of the oral cavity associated with areca nut chewing. Areca nut has been shown to have a high copper content compared to other commonly eaten nuts, and chewing areca nut for 5-30 min significantly increases soluble copper in whole mouth fluids. Our aims were to determine if tissue and serum concentrations of copper were raised in patients with OSF as a result of chewing areca nut. A panel of buccal mucosal biopsies from patients with OSF from Nagpur, India, was used to measure the tissue concentrations of copper by mass absorption spectrometry (MAS). By MAS, the mean tissue copper level was 5.5+/-2.9 microg/g in the OSF specimens (n=11) compared with 4+/-1.9 microg/g in the non-areca chewing controls (n=7) (P=0.2). Energy dispersive x-ray microanalysis (EDX) was used to identify the presence and distribution of the metal element. EDX showed distinct peaks corresponding to copper (Kalpha 8.04 keV; Kbeta, 8.91 keV) in the epithelium (21/23) and in the connective tissue (17/23) of the OSF specimens compared to spectra obtained from control oral biopsies from non-areca chewing subjects (n=7). These findings were confirmed by secondary ion mass spectrometry (SIMS) analysis in a small number of samples. Serum copper (17.23+/-1.80 pmol/l), caeruloplasmin (0.32+/-0.04 g/l) levels and urinary copper (0.52+/-0.26 micromol/l) in OSF patients (n=14) were within the laboratory reference ranges. The finding of copper in OSF tissue supports the hypothesis of copper as an initiating factor in OSF, playing a role in stimulating fibrogenesis by the upregulation of lysyl oxidase activity.

Ultrastructural pathology of the heart in patients with beta-thalassaemia major.

Patients with beta-thalassaemia major frequently suffer from hypersiderosis which leads to hemochromatosis of major organs such as the heart and liver. Little information exists about the ultrastructural pathology of the human heart in beta-thalassaemia patients. Five Cypriot patients with elevated blood ferritin and intractable heart failure were investigated. Cardiac biopsies from these patients were studied by light and electron microscopy, as well as by X-ray microanalysis. Ultrastructural examination revealed the presence of disrupted myocytes showing loss of myofibers, dense nuclei, and a variable number of pleomorphic electron dense granules. These cytoplasmic granules or siderosomes consisted of iron-containing particles as confirmed by X-ray microanalysis. It is likely that the ultrastructural changes observed in myocytes of patients with beta-thalassaemia are largely due to iron deposition.

Ultrastructural and histochemical observations on intracellular and luminal microcalculi in the feline sublingual salivary gland.

As the genesis of salivary calculi in man has not been established, the fortuitous observation of microcalculi in sublingual glands of cats prompted this study. Microcalculi were seen occasionally within acinar cells and lumina and macrophages, and rarely interstitially. Microcalculi were stained with the periodic-acid/Schiff technique, and acid-phosphatase activity was associated with intracellular microcalculi. Intracellular microcalculi were seen ultrastructurally in acinar cells in membrane-bound vacuoles that also contained debris and sometimes what appeared to be secretory material. X-ray microanalysis showed the microcalculi to consist of crystals containing calcium and phosphorus. The observations suggest that the microcalculi form within autophagosomes in acinar cells by a precipitation of calcium and phosphorus present in degenerate material, and that the microcalculi eventually enter lumina, where they may be discharged in the saliva or retained and enlarge.

Scanning electron microscopy of the endometrial cell surface in postmenopausal women receiving oestrogen therapy.

The surface ultrastructure of normal and abnormal endometrial cells from patients receiving oestrogen therapy for the climacteric syndrome was studied by scanning electron microscopy. Patients with endometrial pathology were treated with oral progestogens. Excessive oestrogen stimulation caused proliferation of cilia and microvilli. Cystic hyperplasia was characterised by a proliferation of cilia until they covered more than one-third of the surface area of the endometrium; further proliferation occurred in cases of adenomatous hyperplasia when the surface was almost completely covered with cilia. Cell morphology remained apparently normal until atypical hyperplasia, when occasional cells appeared large and irregular, or adenocarcinoma occurred, when the surface cells appeared large, pleomorphic and sometimes wrinkled, being mostly devoid of cilia. Although cystic hyperplasia was converted to a normal histological picture of atrophic or pseudo-decidual endometrium by courses of progestogen, the deciliated endometrial cells showed persisting abnormal ultrastructural characteristics.