HIV replicates in cultured human brain cells.

Adherent human embryo brain cells have been infected with HIV. Cells replicating HIV were maintained in culture for seven sequential passes over 7 months and continued to produce HIV during that time. Human embryo brain cells displayed glial-cell morphology and expressed glial fibrillary acidic protein. Electron microscopy showed clusters of virus particles around these cells as well as budding virus. Extracted, infected glial cells revealed bands for three major gag proteins, p18, p24 and p55, in Western blotting. It was not possible to detect CD4 antigen on the surface of these cells by indirect immunofluorescence or alkaline phosphatase staining with CD4 monoclonal antibodies. The results of these experiments indicate that HIV replicates in non-malignant brain cells. This observation strengthens the postulated aetiological link between HIV and the encephalopathy, dementia and other neurological symptoms observed in HIV-infected patients.

Hormone replacement therapy in the menopause: a suitable animal model.

Female CBA mice, aged 11 months, were treated cyclically with oral ethynyl oestradiol or oestrone sulphate for 3 months. The ovaries of all animals appeared to be atrophied. Target tissues throughout the genital tract showed a response to both oestrogens. Electron microscopy of both the endometrium and the urothelium demonstrated morphological changes characteristic of increased cellular metabolic activity in the treated mice. Endometrial hyperplasia developed in both treatment groups but more pronounced epithelial changes occurred with oestrone sulphate. This hyperplasia was accompanied by a doubling in the number of uterine cytoplasmic oestrogen receptors. A 50% fall in serum levels of luteinizing hormone in the treated mice revealed that the hypothalamic-pituitary system was still intact. Both oestrogens improved skeletal balance by changes in cortical-endosteal bone remodelling. The results suggest that the CBA strain of mouse is a suitable model for the study of the human climacteric and its response to hormone replacement therapy.

The effects of oestrogen administration on tryptophan metabolism in rats and in menopausal women receiving hormone replacement therapy.

The effects of the administration of oestrogens on the activity of hepatic tryptophan oxygenase have been assessed both directly (by measurement of enzyme activity in vitro) and indirectly (by measurement of urinary excretion of tryptophan metabolites) in rats, and indirectly in menopausal women receiving hormone replacement therapy. Intraperitoneal administration of 500 micrograms of oestradiol or ethinyl oestradiol/kg body wt had no effect on the activity of tryptophan oxygenase in homogenates of liver from mature (13-week-old) female rats. Both adrenalectomy and ovariectomy led to a reduction in the activity of tryptophan oxygenase in homogenates of liver from mature rats; again there was no effect of giving 500 micrograms of oestradiol/kg body wt by intraperitoneal injection. Intraperitoneal administration of 210 micrograms of oestrone sulphate/kg body wt for 1 or 2 days before killing, or its incorporation in the diet for up to 8 weeks at an equivalent dose rate, had no effect on the activity of tryptophan oxygenase in homogenates of liver from ovariectomized 6-14-week-old female rats. Intraperitoneal administration of 500 micrograms oestradiol/kg body wt to intact mature female rats together with 500 mg tryptophan/kg body wt caused a reduction in the urinary excretion of xanthurenic and kynurenic acids, kynurenine and N1-methyl nicotinamide. When peri- and post-menopausal women were treated with ethinyl oestradiol (20 micrograms/day) or piperazine oestrone sulphate (3 mg/day) for 3 months, there was an increase in the concn of tryptophan in plasma, with no change in the urinary excretion of xanthurenic and kynurenic acids and kynurenine. This study provides no evidence for the induction of tryptophan oxygenase by oestrogens in rats or human beings.

Serotonin-immunoreactive cells in the lamina propria plexus of the appendix.

The lamina propria of the human appendix possesses a recently defined ganglionated neural plexus with neurosecretory-type component cells. In order to elucidate the functional role of this plexus, immunohistochemical light and electron microscopic studies were performed on 21 appendixes. By light microscopy, 18 specimens showed within the lamina propria neuron-like and neurosecretory-type cells that stained positively with lead hematoxylin and were positive for serotonin. The number of these cells varied from specimen to specimen. No correlation between the number of serotonin-immunoreactive intraepithelial enterochromaffin cells and the number of plexus cells could be established. Electron microscopic examination revealed identical pleomorphic neurosecretory granules within enterochromaffin cells and plexus cells. The site of serotonin storage in these granules was revealed by electron immunocytochemical methods. It is suggested that, under physiologic conditions, the lamina propria plexus has a modulatory role between the epithelium and the deeper mural enteric nervous system mediated by serotonin neurotransmission. Uncontrolled release of serotonin by the plexus may initiate inflammation and elicit pain related to the appendix.

Somatostatin: a paracrine contribution to hypothyroidism in Hashimoto's thyroiditis.

Thyroid tissue from 18 consecutive cases of Hashimoto's thyroiditis treated surgically were stained immunohistochemically for neurone specific enolase (NSE), somatostatin, calcitonin and thyroglobulin. Cells staining for NSE and somatostatin were present in 14 cases. In four cases large numbers of cells including oxyphil cells stained for NSE. Consecutive sections showed an identical staining pattern of these cells for somatostatin. Sections stained for calcitonin showed few or no positively staining cells. There were moderate numbers of NSE and somatostatin-containing cells in five of the cases, occasional cells in five and none in four cases. Electron microscopy confirmed neurosecretory-like granules within positively staining cells. Somatostatin is known to inhibit T3 and T4 production or release from thyroid cells by a direct action. We suggest, in Hashimoto's disease, somatostatin in paracrine cells serves as a local inhibitory neuroendocrine effector and could be causally related to the hypothyroid state.

A primary tumour of the oesophagus with both melanocytic and schwannian differentiation. Melanocytic schwannoma or malignant melanoma?

A 76 year old white woman presented with a four month history of dysphagia and weight loss. Clinical, radiological, and endoscopic examination revealed a pigmented mass in the lower third of the oesophagus. The preoperative diagnosis, including biopsy examination, was that of malignant melanoma. Following oesophageal resection, the mass was found to be a localised, relatively superficial tumour with light, electron microscopic, and immunohistochemical features common to both Schwann cells and melanocytes. The patient survived 46 months after surgery and died of a stroke, with no evidence of tumour recurrence. The tumour is presented as a case of melanocytic schwannoma, with unique features when compared with oesophageal melanotic schwannomas and malignant melanomas described in the literature. The differential diagnosis is discussed and an origin from a common precursor cell of neural crest origin is postulated.

The renal pathology of primary antiphospholipid syndrome: a distinctive form of endothelial injury.

Some features of the vascular and glomerular pathology of primary antiphospholipid syndrome (APS) are well recognized, but we describe novel glomerular ultrastructural changes that we consider to be pathognomonic of APS. Renal biopsies from eight patients with APS were examined by light and electron microscopy. All had anti-cardiolipin antibodies, and the clinical presentation ranged from fulminant multi-system disease to isolated proteinuria. By light microscopy, the hexamine silver stain showed a combination of glomerular basement membrane wrinkling and reduplication. By electron microscopy, redundant, wrinkled segments of basement membrane were accompanied by a 'new' straighter thin basement membrane adjacent to the endothelium. In two cases the presence of these antibodies was not suspected clinically, and there was no clinical history or evidence of a thrombotic microangiopathy. We describe a distinctive glomerular lesion that represents an unexplained form of endothelial injury in this syndrome.

Cyclosporin nephrotoxicity in heart and lung transplant patients.

Twenty-two patients with heart, lung or heart and lung transplants maintained on cyclosporin for periods ranging from 3 months to 10 years developed renal insufficiency which was investigated by renal biopsy. The histopathological changes were: (i) severe vascular and glomerular damage due to thrombotic microangiopathy (TM); (ii) a form of focal segmental glomerulosclerosis (FSGS); (iii) glomerular ischaemia. Rather than being separate entities, these changes appeared to represent a spectrum of pathology, some biopsies showing all three forms of glomerular injury. In all cases the glomerular changes were accompanied by arteriolar and arterial pathology, and we identified novel ultrastructural changes in the arteriolar endothelial basal lamina. Tubular atrophy was a consistent feature, the severity of which reflected the severity of the glomerular sclerosis, and which appeared to be a consequence of glomerular loss. Our findings are consistent with the nephrotoxic effects of cyclosporin being mediated chiefly via damage to preglomerular vessels and glomerular capillary endothelium. From an analysis of the clinical aspects of these cases, the effects of cyclosporin appear to be to some extent idiosyncratic, and therefore not entirely preventable, but strict monitoring of blood cyclosporin levels is essential to minimize the risk of permanent renal damage. Monitoring urinary protein in addition to plasma creatinine may detect the onset of FSGS, as proteinuria precedes creatinine elevation.

The development of ependyma in the human fetal brain: an immunohistological and electron microscopic study.

The stratified inner layer of the embryonic fetal brain, the ventricular zone (VZ), contains glial fibrillary acidic protein (GFAP)-positive cell bodies of radial glia. The adult cerebral ventricle is lined by a single layer of cuboidal, ciliated common ependymal cells which are, immunohistologically, GFAP negative. In late gestation, the ventricular lining is formed by tanycytes, ependymal cells with short, intensely GFAP-positive basal fibres. The development of ependyma was examined, morphologically and immunohistologically, in human fetal brain from between 11 weeks gestation to 6 months post-term to determine the relationship between the radial glia cell, tanycyte and common ependymal cell. This study was not able to show whether tanycytes were formed from radial glia or were formed from a previously uncommitted population of VZ cells. The study did show, however, that tanycytes probably mature into common ependymal cells following acquisition of cilia and loss of basal fibres. Electron microscopic data indicate that tanycytes have features suggestive of a secretory and/or transport function.

Binovular follicles in the adult human ovary.

The human ovary may contain binovular or polyovular follicles at birth, but they are unusual later in life. Binbovular follicles were found in bilateral ovarian biopsies from a patient with primary amenorrhea who had been treated with exogenous gonadotropins. The fine structural morphology of these follicles has shown that both oocytes were in the resting meiotic prophase, that their respective vitelline bodies faced each other across the intervening plasma membranes, and that the adjacent oocytes made mutual contacts similar to those found between granulosa cells and oocytes. From the appearance of the multivesicular bodies in nearby stromal fibroblasts it is suggested that these follicles had formed by fusion of two adjacent primordial follicles by a mechanism similar to the depolymerization of the ground substance in the apex of the Graafian follicle that leads to ovulation.

[Current opinion on diagnosis of primary Sjögren's syndrome]. / Attualità nella diagnosi della sindrome di Sjögren.

For many years, Sjögren's syndrome was a purely descriptive diagnosis of symptoms such as xerostomia and dry eye (sicca syndrome). The different classification criteria proposed for Sjögren's syndrome comprise a rather variable spectrum of diagnostic possibilities, at one extreme of which we find an array of exclusively objective parameters while, at the other extreme, the objective parameters and patients' symptoms balance out. Improved accuracy in the diagnosis of Sjögren's syndrome can be attained only through the combination of a symptoms questionnaire, histopathology, scintigraphy or sialography or evaluation of the unstimulated salivary flow and specific autoantibodies. In these last few years, further methods have been proposed to increase diagnostic accuracy: the analysis of various salivary constituents, saliva and tear ferning tests, the search for new autoantigens and, above all the use of ultrasonography and magnetic resonance imaging. Color-power Doppler and magnetic resonance sialography have recently been proposed as promising techniques to improve sensitivity and diagnostic specificity. This study discusses the data present in the literature and personal experience regarding diagnostic methods in a group of 350 patients affected by primary Sjögren's syndrome.

Primary localised pleural neurofibroma: expanding the spectrum of spindle cell tumours of the pleura.

AIMS: Primary localised pleural neoplasms are a rare group of thoracic tumours, with solitary fibrous tumour representing the most frequently encountered entity. Two cases of localised pleural neurofibromas involving the pleura are described. METHODS AND RESULTS: The patients were both female: 78 and 29 years of age. In the former a pleural-based lesion was identified on a chest radiograph after she presented with shoulder pain. The second patient was known to have neurofibromatosis type I, and the pleural lesion was found incidentally during excision of a metastatic malignant peripheral nerve sheath tumour of the lung. Both tumours were localised and composed histologically of bland neoplastic spindle cells embedded in a loose collagenous matrix. There was variable immunoreactivity for S100 and CD34, while ultrastructure examination in the two cases showed a mixture of nerve sheath cell types. CONCLUSION: To the best of the authors' knowledge, localised neurofibromas have not been previously reported within the pleura. The presence of a bland spindle cell pleural neoplasm immunoreactive for CD34 may potentially be mistaken for a solitary fibrous tumour. While distinction is usually achieved on close attention to the histological features, staining with S100 protein, especially in small biopsies, should be considered to exclude a neurofibroma.

Multicystic structures appearing in mature cystic teratomas of the ovary: an immunohistochemical and ultrastructural study.

Multicystic or sieve-like areas are frequently present in the walls of mature cystic ovarian teratomas. This histological, immunohistochemical and ultrastructural study supports the contention that such cysts arise from oleous material which has been extravasated through the cyst wall and become lodged within fibrous tissue and small blood vessels. Some cysts may also arise from degenerate sebaceous glands.

Ovarian cystadenofibroma: a consideration of the role of estrogen in its pathogenesis.

A review of 35 cystadenofibromas of the ovary has revealed certain morphological features which implicate the role of estrogenic hormones in the pathogenesis of these neoplasms. The epithelium was tubal in type and at the ultrastructural level was found to be comparable with that of the normal Fallopian tube during estrogenic stimulation. The appearance of the stromal fibroblasts in the connective tissue component of the tumor was also consistent with an estrogenic influence. It is suggested that the source of estrogen responsible for both the epithelial differentiation and the fibrous proliferation may be found in functional steroidogenic cells present in the stroma of the neoplasm.

Neurosecretory cells of the lamina propria of the appendix and their possible relationship to carcinoids.

Carcinoid tumours of the appendix are generally thought to be derived from enterochromaffin cells; in-situ abnormalities of these cells are, however, rarely observed in the mucosal epithelium. One hundred appendices, removed consecutively at surgery, were stained with an alcian blue-PAS diastase-lead haematoxylin sequence and, in 69, cells were found in the lamina propria with a cellular and architectural morphology identical to those of an archetypal appendiceal carcinoid tumour. These cells appeared to contain neurosecretory granules, were diazo-positive and showed argentaffinity. They were further characterized by the localization of cytoplasmic neurone specific enolase and the presence of neurosecretory granules was confirmed by electron microscopy. These cells are designated subepithelial neurosecretory cells (SNC). It is suggested they are an integral component of the subepithelial nervous plexus and are in progenitors of appendiceal carcinoid tumours. A neuroectodermal origin of the SNC-and hence appendiceal carcinoid tumours-is proposed.