Biomedical subjects
Publications and source records attributed to T Gray.
A case of peripheral neuroepithelioma arising from the trigeminal nerve in Meckel's cave is presented. The discussion emphasizes the pathological criteria for the diagnosis of a peripheral neuroepithelioma and the current controversy about the classification of this and related tumors.
Renal histopathological changes in rats, caused by food partially moulded by a common fungus isolated from an area of nephropathy in Yugoslavia, were differentiated into acute and chronic responses. The acute response to a few days on the diet specifically involved necrosis and concomitant mitosis in proximal tubule cells. More protracted, continuous or intermittent administration of nephrotoxic mould led to a marked karyomegaly in the same corticomedullary region. The phenomenon is more prominent than that induced by treatment with ochratoxin A over a similar period, raising the question of the putative role of such mycotoxins in the etiology of chronic human renal disease.
Two community studies of campaigns conducted in the Illawarra Area of New South Wales demonstrate how GPs can successfully participate in structured public health initiatives. This approach is felt to bring benefits to the patient, the participating GP, and the wider community, and serves as a model for increased involvement in such programmes.
The question being examined is whether one or more morphologically distinct cell types can be identified in the conducting airways of adult rabbits possessing stem cell functions. The term "stem cell" is used to denote cells with extensive self-replicating potential and the ability to produce differentiated progeny. According to various models of cell renewal in the conducting airways that have been proposed over the years, two different cell types have to be regarded as primary candidates for the stem cell: basal cells and some type of secretory cells. The question is complicated by the fact that significant differences exist between species in the distribution and morphological characteristics of airway cell types. In addition, different airway segments may or may not be occupied by different populations of stem cells. Previously, investigators have addressed the problem by studying normal cell regeneration or injury induced cell regeneration in vivo in the whole animal. We decided to attempt a different approach, namely, to separate specific cell types and to study the proliferation and differentiation capacity of such cell isolates using in vitro and in vivo cell culture techniques. Our studies lead us to conclude that the conducting airways of adult rabbits contain at least two distinct cell populations endowed with stem cell potential, namely basal cells and bronchiolar Clara cells. From that it follows that the trachea and bronchi, on one hand, and the bronchioles, on the other hand, are occupied by two different stem cell populations governing renewal of the epithelial lining.
The clinical, radiological and pathological features of eight cases of supratentorial primitive neuroectodermal tumour are reviewed. These are tumours of children and young adults presenting with symptoms and signs of raised intracranial pressure. Radiologically they are characterized by a large enhancing mass lesion exciting little or modest surrounding oedema, with a propensity to develop in the frontal lobes. One tumour exhibited the pathological features of a primitive neuroectodermal tumour (PNET) with ependymal differentiation (ependymoblastoma). The rest showed no light microscopy patterns to indicate differentiation. Immunohistochemistry was helpful as it excluded other causes of a 'small blue cell' tumour but did not help in assessing differentiation. Ultrastructural examination of this group of apparently undifferentiated tumours showed focal markers of neuronal differentiation. Although features of neuronal differentiation can be found ultrastructurally in these tumours this is only evident after prolonged searching, often of several blocks, making assessment very prone to sampling errors. The term PNET thus remains appropriate and serves to group such tumours together to facilitate rational clinical management.
The abilities of various dioxins to induce toxicity or transformation of rat tracheal epithelial cells in culture were examined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was not cytotoxic and did not induce transformation as measured by the induction of growth-altered, preneoplastic cells (termed enhanced growth variants). However, TCDD enhanced the transformation of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated rat tracheal epithelial cells. Other dioxin congeners with 0 to 3 chloro substitutions were inactive in enhancing MNNG transformation. TCDD was most effective at a concentration of 0.3 nM and when treatment was administered immediately after MNNG exposure. The dose-response curves for enhancement of MNNG-induced transformation and induction of aryl hydrocarbon hydroxylase activity by TCDD were similar. These results are consistent with the hypothesis that the enhancement of cell transformation by TCDD is mediated through the TCDD receptor. TCDD also enhanced transformation when the cells were treated before MNNG treatment. The ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) to enhance MNNG-induced rat tracheal epithelial transformation was also examined. In contrast to the findings with TCDD, the number of transformed colonies was increased only by pretreatment with TPA followed by MNNG. TPA-pretreatment enhanced equally the number of normal cells forming colonies and the total number of transformed colonies after selection; therefore, the transformation frequency (transformants per total surviving colonies) was unchanged by TPA. In contrast, TCDD treatment enhanced the transformation frequency in MNNG-exposed cultures since the number of transformed colonies increased while the number of total colonies remained constant. Thus, TCDD appears to act by a different mechanism than TPA. TCDD enhancement of MNNG-induced transformation may be attributed to a promotional effect, a comutagenic action, or a modulation of cell proliferation and/or differentiation mediated through the TCDD receptor.
Morphological observations suggest that rate tracheal epithelial (RTE) cells undergo squamous differentiation when maintained in cell culture. The purpose of the studies presented here was to examine and define differentiation of cultured RTE cells with the help of markers previously shown to be specific for squamous differentiation. Furthermore, we wanted to determine whether neoplastic transformation of these cells causes significant disruption of their differentiation program. Our experiments showed that squamous differentiation occurs in normal primary RTE cell cultures. Epidermal transglutaminase (transglutaminase type I) activity increased approximately 20-fold in RTE cultures as a function of time. Cholesterol sulfate, another marker of squamous differentiation, increased only modestly with time. A significant number of cells formed cross-linked envelopes in cultures growth-arrested at a cell density of approximately 250 cells/mm2. However, no significant changes in keratin expression were detected. Neoplastically transformed RTE cells which exhibit a greatly increased growth capacity expressed the same three markers of squamous differentiation as normal RTE cells. However, transglutaminase type I activity was relatively low. The cross-linked envelope formation was independent of cell density in the transformed cells. Like in normal RTE cultures, cholesterol sulfate accumulation only increased moderately with increasing cell density. The keratin pattern of transformed RTE cell lines was identical to that of normal primary RTE cells. A well-differentiated squamous cell carcinoma derived from one of the neoplastic cell lines expressed in vivo keratin markers typical of keratinization (56 kd acidic keratin and 65-67 kd basic keratins). We draw the following conclusions. (i) The biochemical studies confirm that normal RTE cells undergo squamous differentiation. The pathway of terminal squamous differentiation is cell density dependent. (ii) In transformed RTE cells, growth as well as differentiation are less subject to regulation by cell density than in normal cells. (iii) Transformed RTE cells are differentiation competent; the main abnormality appears to be that in transformed cell populations proliferation and differentiation occur concomitantly.
Studies were performed to examine the hypothesis that the basal cells in the large conducting airways function as stem cells. Basal cells were isolated from the tracheas of adult rabbits using centrifugal elutriation procedures. Such cell isolates that contained greater than 90% basal cells were plated in culture at low cell density to produce individual basal cell clones. Clones were similarly obtained from unfractionated tracheal cells (mixed tracheal cells). Basal cell and mixed cell clones were tested to compare their in vitro growth capacity and their ability to reepithelialize denuded tracheal grafts with a mucociliary epithelium. Both basal cell and mixed cell clones underwent 15 to 20 population doublings in culture. The sizes of their clonogenic cell compartments were roughly similar. When inoculated into denuded tracheal grafts, both types of clones were equally efficient in establishing a mucociliary epithelium. The major secretory cell types observed in tracheas repopulated with the two types of cell clones were cells containing small secretory granules and either rough or smooth endoplasmic reticulum. Goblet cells were seen in approximately 40% of tracheas repopulated with either of the two types of cell clones. It is concluded that in rabbits tracheal basal cells can generate secretory cells with varying morphologic characteristics as well as ciliated cells and may be regarded as epithelial stem cells.
Using an immunocytochemical method to localise antibodies to ubiquitin, filamentous inclusion bodies were seen in spinal anterior horn neurones in cases of motor neurone disease (MND) but not in any control cases. These inclusion bodies appeared to be closely associated with classical Bunina bodies and immuno-electron microscopy suggested that they were based on arrays of straight 10-15 nm filaments together with some granular material. These observations link the protein ubiquitin with a chronic neurodegenerative disease and extend previous observations of a close association between filamentous inclusion bodies and ubiquitin. Ubiquitin-filament inclusions should be regarded as a new hallmark in the histological diagnosis of MND.
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The objective of this study was to examine the differentiation potential of basal cells purified from rabbit tracheas by means of centrifugal elutriation. Cell suspensions containing between 83 and 94% basal cells were inoculated into tracheal grafts denuded of their own epithelium and transplanted to the backs of nude mice. Within 1 week after inoculation, the basal cells reestablished a continuous poorly differentiated epithelial sheet which at 2 to 4 weeks showed typical mucociliary differentiation. Basal cells, ciliated cells, goblet cells, and secretory cells with small granules were present. Some of the latter contained abundant rough endoplasmic reticulum and others contained predominantly smooth endoplasmic reticulum. These data indicate that basal cells can give rise to all major tracheal cell types suggesting that they are the main stem cell in the large airways of rabbits.
The arrangement of tissue in the internal elastic lamina of muscular pulmonary arteries in rats has been studied. It consists of long plates of elastic tissue joined to each other by side branches, thus forming a continuous branching network. The thick plates are orientated parallel to the long axis of the vessel. This is similar to the arrangement in the saphenous and splenic veins in the dog. Systemic arteries show a different arrangement, usually a single fenestrated sheet. The differences between systemic and pulmonary arteries can be explained by considering the different biomechanical forces acting on them.
We describe a method for the ultrastructural localization of surface markers on cells in intact tissue sections. Using a primary monoclonal antibody to a surface marker followed by a second stage gold-labelled antibody, surface antigens can be specifically localized. This enables cellular interactions to be studied in solid tissues.
The purpose of our studies was to examine the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on survival, proliferation, and differentiation of normal and preneoplastic rat tracheal epithelial (RTE) cells. Normal RTE cells obtained from 8-week-old rats were plated into medium containing TPA at concentrations ranging from 0.1 to 100 ng/ml. A dose-related increase in colony-forming efficiency (CFE) was observed at concentrations above 0.1 ng/ml. At 100 ng/ml the CFE was increased 5-fold above that observed in controls. Similar studies were carried out with immortal, preneoplastic RTE cells derived from carcinogen-exposed primary cultures. Upon exposure to 10 ng/ml of TPA, 9 out of 11 cell lines showed a marked decrease in CFE ranging from a 70 to a greater than 99% reduction. Two out of 11 cell lines showed only a minor reduction in CFE at this TPA concentration. Teleocidin B was as potent as TPA in causing inhibition of CFE in preneoplastic RTE cells; the potency of 4-O-methyl TPA was approximately 1/100 that of TPA and phorbol was virtually inactive. Further studies suggested that inhibition of clonal growth of the preneoplastic tracheal cells by TPA was due to rapid cell death. As early as 2 h after addition of TPA to the cultures, a loss of viable cells from the cultures as well as a reduction in CFE was observed. Morphological studies support the interpretation that a large number of cells was severely damaged within 2--4 h after TPA exposure. The formation of cross-linked envelopes (CLE), a measure of keratinocyte differentiation, was determined in cultures of preneoplastic RTE cells. TPA caused only minor increases in CLE formation indicating that the cells were not dying from TPA-induced terminal keratinocyte differentiation, but rather from TPA toxicity. Thus, preneoplastic RTE cells respond differently to TPA from normal RTE cells and also from normal and transformed keratinocytes of various origins. The role of TPA toxicity in promoting preneoplastic RTE cells to the neoplastic state is being investigated.
We report a patient with a transellar intercavernous carotid anastomosis associated with right-sided descending aorta and agenesis of the internal carotid artery. To our knowledge, such an association has not been reported previously. Findings at angiography, computed tomography (CT) and dynamic CT are presented. We suggest that dynamic CT is not a reliable method of excluding this anomaly, a fact that has relevance to investigation prior to transphenoidal surgery for pituitary adenoma.
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The clinical presentation of sphenoid sinus mucocele is usually dependent on the degree of involvement of adjacent structures. Since extension can be in any direction, there is a wide spectrum of symptomatology and clinical diagnosis can be difficult. Five cases of sphenoid sinus mucocele, four of which were demonstrated by computed tomography (CT), are presented. CT with its multiplanar display capability, is the diagnostic procedure of choice. It not only demonstrates the extent of the lesions non-invasively, but its ability to demonstrate bony expansion and destruction as well as density and enhancement pattern, will obviate the need for tomography. It has the greatest potential for differentiating other sphenoid and parasellar lesions.
We report a 69-year-old woman with a spinal meningeal arteriovenous malformation (AVM) supplied entirely from the internal iliac artery. In addition, the patient also had a tethered cord and a sacral fibromuscular cyst. To our knowledge, this is the second patient reported with such an association.