Enlargement Of Intercellular Spaces Research Articles

Biochemical and ultrastructural studies in the neural retina and retinal pigment epithelium of STZ-diabetic rats: effect of captopril.

We measured the activities of total Na+, K+-ATPase (Na, K-ATPase), its alpha1 and alpha2/alpha3 isoforms and the angiotensin-converting enzyme (ACE) in the microvascular and neural compartments of the retina, and/or retinal pigment epithelium (RPE) of streptozotocin (STZ)-diabetic rats. The effect of captopril, an ACE inhibitor on Na, K-ATPase activities was also determined and correlated to morphological changes. Insulin-dependent diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg) in male Long-Evans rats. ACE activity was inhibited by captopril (10 mg/kg given in the drinking water) for 1 month. Na, K-ATPase activity was measured spectrophotometrically or by a radioassay (32P-labeled ATP). The activity of ACE was determined by a radioassay using tritiated benzoyl-gly-gly-gly as substrate. Both the alpha1 and alpha2/alpha3 isoforms of Na, K-ATPase were present in the microvascular and neural compartments of retinas, whereas only one isoform, the alpha2/alpha3, was found in the RPE. In 2-month diabetic rats, the activity of the alpha2/alpha3 isoform was reduced in both the microvascular and neural compartments of retinas, while the activity of the alpha1 isoform was reduced only in the neural isolates. ACE activity was significantly decreased in the retinal neural compartment and unaltered in the microvascular compartment from 2-month diabetic rats. In 5-month diabetic rats, Na, K-ATPase activity was moderately but not significantly reduced in RPE preparations. Ultrastructural studies revealed a significant deepening of basal infoldings in the RPE and a noticeable increase in the size of the extracellular space between the basal infoldings of 5-month diabetic animals. Captopril stimulated Na, K-ATPase activity in the neural retina, but not in the RPE. Diabetes-induced morphological changes in the RPE were not improved by captopril. An enlargement of intercellular space between the RPE cells was a frequent finding in the treated group. In conclusion, captopril stimulated Na, K-ATPase activity in the neural retina of diabetic rats. This stimulation seems to be beneficial to the neural retina. ACE inhibition, however, did not improve RPE morphological changes. Although the clinical significance of increased intercellular spacing between RPE cells in treated animals is not clearly established, we speculate that it might contribute to an increased alteration of their barrier function. Additional studies are necessary to assess both the desirable and adverse effects of captopril and other ACE inhibitors in the retinas of diabetic patients.

Ultrastructural alterations of choroid plexuses of lateral ventricles of rats (Rattus norvegicus) submitted to experimental chronic alcoholism.

Adult male rats (Wistar lineage) were alcoholized with sugar cane liquor diluted at 30(0) GL during 300 days and sacrificed every 60 days in 5 stages. Samples of choroid plexuses of lateral ventricles were collected and examined at transmission electronic microscope to detect possible ultrastructural alterations and to raise possible pathological correlations. Gradual changes were observed in these animals during all the experiment: dilatation and enlargement of cisternae of Golgi complex, dilatation of RER, presence of digestive vacuoles and a large amount of pinocytic vesicles as well as vesicles with electronlucent content throughout cytoplasm, as well as an enlargement of intercellular space between basolateral interdigitation of the cells and of the connective tissue. The changes observed in the epithelium and connective tissue of choroid plexuses specially in 240 and 300 days of treatment are presumably due to a disturbance in hydroelectrolitic homeostasis, contributing to several morpho-functional disturbs of central nervous system. No changes were observed in the control group animals.

Cholera toxin-induced secretion in rats is reduced by a soluble fiber, gum arabic.

Gum arabic (GA), a soluble fiber with emulsifying properties, enhances intestinal water and electrolyte absorption in normal and secreting rats. Our aim was to assess the effect of GA, 2.5 and 5.0 g/liter, on cholera toxin-induced water and electrolyte secretion in rat jejunum in vivo. After a 2-hr exposure to cholera toxin, jejunal segments of adult rats were perfused in vivo with at plasma electrolyte solution containing GA, 0, 2.5 or 5.0 g/liter. 24Na was used as a marker of sodium influx. Cholera toxin-induced secretion was reduced by GA, 2.5 and 5.0 g/liter. 24Na secretion into the lumen was reduced by GA. GA caused a morphological expansion of intercellular spaces in the villi but not crypts. In conclusion, GA promotes lumen to blood intestinal transport of water and sodium despite cholera toxin activation. These observations support a potential role for GA in enhancing the efficacy of ORS.

Morphological Changes in Rabbit Corneal Endothelium After Surgical Injuries

Purpose: To understand the responses of the corneal endothelium to different types of surgery, we chronologically investigated the morphologic changes in the endothelial cells. Methods: We did a mechanical incision, epithelial ablation, and excimer laser radiation on rabbit corneas and observed the morphologic changes in the endothelial cells for up to 2 weeks after surgery under a light microscope and an electron microscope. Results: Although we observed enlarged intercellular spaces between neighboring endothelial cells, intercellular adhesion kept the cells tightly joined near their apexes immediately after each procedure. No signs of endothelial cell degeneration were observed after the procedures, but we did observe many Golgi apparati, rough-surfaced endoplasmic reticula, and secreted granules, indicating that the cells had been activated. After each procedure, the intercellular junctions and spaces required different amounts of time to return to normal. Conclusions: These results suggest that the different kinds of surgical injuries affected the corneal endothelium but that the changes were reversible. (J Jpn Ophthalmol Soc 103:350–355, 1999)

Chlorpyrifos elicits mitotic abnormalities and apoptosis in neuroepithelium of cultured rat embryos.

Chlorpyrifos is used increasingly as a pesticide in place of more toxic alternatives such as parathion. Although chlorpyrifos is not a potent dysmorphogen, recent reports that fetal or infant exposures may exceed acceptable limits have raised concern about the potentially more subtle effects on brain development. In the current study, whole rat embryo culture was used to study the effects of chlorpyrifos at the neural tube stage of development. On embryonic day 9.5, embryos were exposed to 0.5, 5, or 50 micrograms/ml of chlorpyrifos. After 48 hr (embryonic day 11.5), embryos were examined for dysmorphogenesis and were then processed for light microscopic examination of the neuroepithelium. Examination of 1-micron-thick toluidine blue-stained sections of the forebrain and hindbrain region revealed reduced and altered mitotic figures, with dispersion and disorientation of the mitotic layer. In addition, cytotoxicity was evidenced by cytoplasmic vacuolation, enlargement of intercellular spaces, and the presence of a significant number of apoptotic cells. These alterations were evident even at the lowest concentration of chlorpyrifos, which produced no dysmorphogenesis. The effects were intensified at higher concentrations, which were just at the threshold for dysmorphogenesis; the neuroepithelial abnormalities, however, were still present in embryos that were not dysmorphogenic. Our results in rat embryo culture support the idea that chlorpyrifos specifically targets brain development at low concentrations, indicating the need to reevaluate the safety of this compound for exposure in vivo.

Leydig Cell Functional Structure and Plasma Androgen Level during the Decline in Fertility in Aging Roosters

In roosters, fertility peaks to 96% at 32 weeks, shortly after sexual maturation, and then declines rapidly to 68% at 70 weeks and to less than 10% at 110 weeks, as a result of intratesticular retention of spermatozoa. The reduction in fertility is associated with functional structural changes of the interstitial tissue, reflected in decreased plasma androgen levels from 2.7 ng/ml at 32 weeks to less than 0.5 ng/ml at 110 weeks. In high fertility roosters, the interstitial tissue is tightly packed with Leydig cells, which contain relatively large amounts of rough endoplasmic reticulum and lipid droplets, both related to androgen synthesis. In the old rooster, which has a low fertility, the interstitial tissue contains only occasional Leydig cells within an enlarged intercellular space. These Leydig cells contain small amounts of endoplasmic reticulum, mainly rough, and there are low plasma androgen levels. It is concluded that differentiation of roosters' interstitial tissue is reflected by plasma levels of androgen. This, in turn, is related to the mechanism of spermatozoa release from Sertoli cells and, consequently, with the level of fertility.

Horseradish peroxidase permeation from the capillaries of the stria vascularis after inoculation of endotoxin into the middle ear.

Escherichia coli-derived endotoxin was inoculated in the middle ear of guinea pigs 24 hours after being injected intraperitoneally. Twenty-four hours after the middle ear inoculation, horseradish peroxidase (HRP) was injected via the femoral vein and the permeability of HRP through the capillaries of the stria vascularis and the destination of the leaked HRP were examined. A large amount of HRP leaked out of the capillary through he opened endothelial cell junctions and penetrated the enlarged intercellular spaces. Leaked HRP entered the pinocytotic vesicles of the intermediate cells. Even slightly degenerated intermediate cells retained this function. The HRP penetrated the spongelike structure of the marginal cells leading to the intercellular space. This structure was not observed without endotoxin. The HRP could not pass the cochlear duct through the tight junctions between marginal cells. Blood sludging was observed in the strial capillaries. It appeared more frequently in the upper three turns than in the basal turn. The HRP leakage out of the capillaries was observed not only in the upper three turns but also in the basal turn.

Immunohistochemical and ultrastructural study of adult porcine endocrine pancreas during the different steps of islet isolation.

Treatment of diabetes mellitus by transplantation of isolated pancreatic islets could constitute an alternative to human pancreas allograft. Before transplantation, porcine islets are submitted to a procedure of isolation and purification. The quality of islets through these different steps may be assessed by morphological and functional studies. The aim of this work was the histological characterization of the four main cell types of porcine adult endocrine islets during the different steps of the isolation procedure using immunohistochemistry (IHC) applied in light (LM) and electron microscopy (EM). In fresh pancreas, islets were various sizes and shapes in LM. The number was not found different between the different portions of the pancreas. In IHC, insulin (Ins)-secreting cells accounted for the majority of the islet cells, while glucagon(Glu)-somatostatin (Som)- and polypeptide(PP)-immunoreactive cells, in decreasing number, were found in the mantle around the core of Ins-cells. In EM, B-cells contained poly-hedric granules with a dense central core and clear halo. Glu granules were spherical and very dense. D-cells and PP-cells were characterized by numerous granules, rather spherical and of inequal density for Som and more ellipsoidal for PP granules. After purification in Euroficoll, in EM, the four cellular types remained recognizable, but underwent vacuolization, mitochondrial swelling, and enlargement of intercellular spaces. After 3 days of culture on plastic dishes, as on Biopore membranes in a Millicell insert, microvilli appeared and vacuolization increased in EM. At the seventh day of culture, in EM, most of the cells were lysed in contrast to LM where at the same time, the four cell types were clearly identified by IHC but only in collagen matrix. Important discrepancies were noticed between LM and EM. This fact emphasizes the complementarity of morphological and functional studies in assessment of the quality of an islet isolation.

Response of guanylate cyclase to atrial natriuretic factor in epithelial cells of the frog choroid plexus

This study shows that the choroid plexus of Rana esculenta contains a guanylate cyclase particulate (GCp), similar to that identified in Mammalia, that is quite sensitive to the atrial natriuretic factor (ANF). The cytochemical tests for GCp show that ANF increases the enzymatic reaction products. Deposits are observed on the apical portion, at the basal level and along the lateral edges of the epithelial cells, with the exclusion of some intercalary epithelial cells with reaction-lacking microvilli. In particular, ANF seems to intensely stimulate the GCp activity along the lateral membranes of the epithelial cells delimiting enlarged intercellular spaces, which are probably dilated for the transport of water and solutes. These data confirm the osmoregulatory role of the hormone and its control of cephalorachidian liquid composition.

Ultrastructure of Contusion Cataract

We investigated the histopathologic condition of four lenses with contusion rosette cataract by light and electron microscopy; periods between blunt trauma and cataract extraction varied from 4 months to 40 years. The initial morphologic changes appear to be the formation of intercellular vacuoles within the lens epithelium and the swelling of superficial cortical lens fibers. Signs of beginning fiber degeneration within the edematous zone include fragmentation of fiber cytoplasm into droplets and globules, formation of abnormal membrane arrangements, and enlargement of intercellular spaces. Late rosette opacities manifest as sharply demarcated layers of vacuolic degeneration in the deeper cortex. We suggest that in contusion cataract, a traumatically induced dysfunction of the lens epithelium leads to an edema of superficial cortical lens fibers that subsequently undergo degeneration and produce a localized and permanent lamellar zone of vacuolation. With time and with the formation of new clear lens cells, this layer becomes gradually compressed and displaced deeper into the cortex.

Characterization of ultraviolet radiation-induced damage to keratinocytes in a skin equivalent in vitro.

The human skin equivalent (HSE) provides a convenient model for studying the dermatological effects of exposure to ultraviolet (UV) radiation. HSEs, constructed by overlaying a collagen-fibroblast matrix with epidermal cells, were maintained submerged for 1 week after the addition of epidermal cells and then raised to the air-liquid interface for an additional 3 weeks. HSEs were exposed to sublethal doses of UV radiation ranging from 0 to 500 J/m2, incubated up to 48 h in medium containing 3H-thymidine and fixed for ultrastructural and autoradiographic analysis. Exposure to radiation doses greater than 50 J/m2 led to vacuolation of the cornified envelopes and enlargement of intercellular spaces. These doses also led to the formation of dense cytoplasmic bodies, and separation and vesiculation of the nuclear envelope in the basal cells. DNA synthesis in the basal cells was analyzed autoradiographically. Maximal numbers of labeled basal cells were observed 24 h after exposure to UV radiation at 50 J/m2. Although the proportions of labeled cells varied among different epidermal donors, the maximal responses and time-course of 3H-thymidine incorporation remained consistent, supporting the usefulness of the HSE in studying the effects of UV irradiation on human skin.

Differential cell enlargement and its possible implication for resupination in Lemboglossum bictoniense (Orchidaceae)

Changes in the structural features of cell populations in the pedicel of Lemboglossum bictoniense (Bateman ex. Lindley) Halbinger were examined by means of light microscopy in relation to resupination, a twisting of the pedicel through 180o prior to flower opening. Serial sections in transverse and longitudinal planes were taken from pre-resupinate and fully resupinate pedicels of flowers from a single inflorescence, and comparisons made between the tissues. The pedicel is a prismatic cylinder flattened on three sides, producing three distinct ribS. Each rib contains one central vascular bundle enclosed by cortical parenchyma. Intervening cortical parenchyma forms flanks external to a central core of three vascular bundles, each of which is split into three distinct traces at this level. Resupination is accompanied by axial and radial expansion of cortical parenchyma. Specialized raphide-bearing cells in the cortex expand axially doubling their length in the ground parenchyma. These raphide cells are localized in the rib cortex, and their expansion is reflected in greater elongation of the ribs relative to flank areas. The extra rib length is accommodated by a lateral displacement (twisting) of the ribs around the central axis of the pedicel. Tissue distortion is reduced by cell division, expansion of intercellular spaces and a radial contraction of pith parenchyma. Raphide cell elongation could be a contributing factor in pedicel twisting. The direction of resupination may be controlled by the organization of these cells into arcs on one or other side of the rib vascular bundle.

Differential cell enlargement and its possible implication for resupination in Lemboglossum bictoniense (Orchidaceae)

Changes in the structural features of cell populations in the pedicel of Lemboglossum bictoniense (Bateman ex. Lindley) Halbinger were examined by means of light microscopy in relation to resupination, a twisting of the pedicel through 180° prior to flower opening. Serial sections in transverse and longitudinal planes were taken from pre-resupinate and fully resupinate pedicels of flowers from a single inflorescence, and comparisons made between the tissues. The pedicel is a prismatic cylinder flattened on three sides, producing three distinct ribs. Each rib contains one central vascular bundle enclosed by cortical parenchyma. Intervening cortical parenchyma forms flanks external to a central core of three vascular bundles, each of which is split into three distinct traces at this level. Resupination is accompanied by axial and radial expansion of cortical parenchyma. Specialized raphide-bearing cells in the cortex expand axially doubling their length in the ground parenchyma. These raphide cells are localized in the rib cortex, and their expansion is reflected in greater elongation of the ribs relative to flank areas. The extra rib length is accommodated by a lateral displacement (twisting) of the ribs around the central axis of the pedicel. Tissue distortion is reduced by cell division, expansion of intercellular spaces and a radial contraction of pith parenchyma. Raphide cell elongation could be a contributing factor in pedicel twisting. The direction of resupination may be controlled by the organization of these cells into arcs on one or other side of the rib vascular bundle.

Ultrastructural study of the ovary of the sessile scyphozoan, Haliclystus octoradiatus (Cnidaria: Stauromedusae).

An ultrastructural study of the ovary of the sessible jellyfish, Haliclystus octoradiatus, indicates that it is fundamentally different from that of other scyphozoans and is the most structurally complex within the class. Oocytes develop within a series of spherical, sac-like ovarian follicles consisting of an enlarged intercellular space between two layers of subumbrellar gastrodermis. Developing oocytes are largely restricted to a thin germinal epithelium at the periphery of each follicle and gradually migrate toward the lumen as they mature. Individual oocytes are surrounded by early germ cells and follicle-like accessory cells of presumed somatic origin. Similar folliclelike cells have not been described in the Cnidaria previously. Vitellogenesis appears to involve the combined activity of the Golgi complex and associated rough endoplasmic reticulum. Ovarian morphology may be helpful in deciphering phylogeneitc relationships within the Cnidaria. © 1993 Wiley-Liss, Inc.

Photophysiology of turion germination in Spirodela polyrhiza (L.) schleiden. XI. Structural changes during red light induced responses

Summary Germination response as well as de-etiolation (chlorophyll fluorescence in vivo ), induced by irradiation with continuous red light (cR), were investigated in etiolated, photodormant turions of Spirodela polyrhiza . Structural changes during these physiological reactions were revealed by light and electron microscopy. Two different developed embryonic-like organs (frond primordia) were found and characterized in greater detail. One of the earliest cytological changes within these primordia after light-induction was the formation of dictyosomes, absent before cR irradiation. Enlargement of intercellular space during the first 48 h of cR irradiation pointed to cell elongation as the primary process on the cellular level. Cell division was demonstrated in the subsequent period (72 h cR) in parallel with the visible emergence of the new sprout. Disappearance of prolamellar bodies and formation of chloroplasts within the primordial cells was demonstrated before visible germination was detectable. The starch content of these plastids was increased within the pre-germination period, especially in apical cells. Therefore, carbohydrate translocation from the storage tissue to the frond primordia was postulated.

Methotrexate-induced developmental toxicity in rabbits is ameliorated by 1-(p-tosyl)-3,4,4-trimethylimidazolidine, a functional analog for tetrahydrofolate-mediated one-carbon transfer.

Dihydrofolate reductase reduces folic acid to tetrahydrofolate as a prerequisite to one-carbon metabolism, which is required for normal embryonic de novo DNA synthesis. The developmental toxicity of methotrexate (MTX) has been attributed to MTX's ability to inhibit the activity of dihydrofolate reductase and thereby indirectly suppress one-carbon metabolism. The compound 1-(p-tosyl)-3,4,4-trimethylimidazolidine (TTI), which is structurally unrelated to folate, reestablishes one-carbon metabolism by the biomimetic transfer of single carbon units. Whether the developmental toxicity of MTX is indeed caused via suppressed one-carbon metabolism was tested in New Zealand white rabbits following concurrent maternal treatment with MTX and TTI. TTI reduced MTX developmental toxicity judged by increased mean fetal body weights, decreased percentage of malformed fetuses, and reduced incidences of major malformations. Two doses of TTI (90 mg/kg, each) at 1 hr prior to and 1 hr after MTX also reduced the developmental toxicity, but was no more effective than the single-injection regimen. Treatment with TTI alone caused no developmental toxicity. Histologically, MTX caused enlarged intercellular spaces in limb bud mesenchyme that began at 6-8 hr and increased in size until 16 hr. Mesenchymal nuclei appeared basophilic, with angular contours. Pretreatment with TTI delayed MTX-induced histological changes until 20-24 hr after MTX in 36-50% of embryos and completely protected the remainder. The sequence of MTX-induced changes was not altered among affected embryos, although the severity of the lesions did not appear as great. Saline-only or TTI-only treatments caused no alterations in limb buds. These data are consistent with the concept that impaired one-carbon metabolism is indeed the fundamental process underlying MTX developmental toxicity.

Changes in the choroid plexus, responses by intrinsic epiplexus cells and recruitment from monocytes after experimental head acceleration injury in the non-human primate.

We have examined, by scanning and transmission electron microscopy, morphological changes in the choroid plexus of the lateral ventricles of the non-human primate brain after lateral head acceleration. We demonstrate passage of plasma and blood cells either through tears in blood vessels and the choroidal epithelium, or through the cells of the choroidal epithelium, 20 min after injury, together with morphological changes in that epithelium. At 3 and 4 h small cells with a reniform nucleus accumulate in the connective tissue core of the choroid plexus. We suggest that these are monocytes. At 6 and 12 h cells can be seen in enlarged intercellular spaces within the choroidal epithelium. These cells possess surface ruffles and we suggest that they are monocytes differentiating into macrophages and epiplexus cells. Further evidence for transepithelial migration of monocytes/macrophages is obtained at 7 days. However, at 28 days all blood has been removed from the surface of the choroid plexus and epiplexus cells possess an appearance typical of that in uninjured animals. The possible sources of epiplexus cells are discussed with reference to studies of responses after brain insult and of development. We have obtained no evidence in support of emperipolesis by monocytes through the choroidal epithelium. We suggest that monocytes/macrophages migrate, via an intercellular route, to differentiate into epiplexus cells, thus providing additional numbers of epiplexus cells after head injury.

Morphological and Histochemical Effects of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) on Marmoset (Callithrix Jacchus) Testes

The testes of marmosets (Callithrix jacchus), which had been treated with a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.3 microgram to 10 micrograms/l kg body weight (BW)) were studied after 7 days using morphological and histochemical techniques. Light microscopic and electron microscopic examination revealed decreased intercellular contact in the germinal epithelium, as indicated first by enlarged intercellular spaces between the Sertoli's cells and between the Sertoli's cells and neighboring germ cells (i.e., spermatogonia and preleptotene spermatocytes), particularly in the basic compartment of the germinal epithelium. Second, decreased intercellular contact was indicated by the accumulation of premature spermatids and spermatocytes in the tubular lumen after TCDD treatment. The Sertoli's cells exhibited an increased amount of lipids, phagolysosomes, and vacuoles in their cytoplasm. Spermatids were frequently affected by TCDD, particularly during early spermiogenesis. These alterations included vacuolization of the cytoplasm and the development of additional germinal vesicles. This special effect on spermiogenesis became even more evident quantitatively by determination and counting of tubular stages in semithin sections. Tubular determination on the basis of the appearance of spermatids revealed that the ratio of tubular stages I to III became lower and that of stages V to VII became higher, dose dependently, indicating a maturation stop at the beginning of spermiogenesis caused by TCDD treatment. After TCDD treatment, Leydig's cells were morphologically unaffected, but histochemical investigations revealed decreased activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). The sensitivity of the applied methods was different in view of the level of unaffection. The effect of Leydig's cells, as indicated by the decreased activity of 3 beta-HSD, had already been found at a dose of 1 microgram/kg BW TCDD, whereas clear-cut morphological and morphometrical effects were seen at 3 micrograms/kg BW for the first time. Moreover, with the special effect on spermiogenesis in marmoset monkeys, the findings demonstrate that the toxicity of TCDD on testicular morphology is species specific.

Spirochetes in early lesions of necrotizing ulcerative gingivitis experimentally induced in beagles

The presence of spirochetes and other bacteria during the induction of necrotizing ulcerative gingivitis (NUG) in beagle dogs was studied by transmission electron microscopy. NUG was induced by application of dental debris from diseased dogs to 4 beagles treated with corticosteroid. Biopsies of interdental papillae were collected during a period of 7 weeks. Spirochetes and other bacteria were observed in enlarged intercellular spaces between non-keratinized epithelial cells. Intracellular bacteria were found with and without surrounding vesicular spaces. The invasive spirochetes were mainly intermediately sized and of flagellar "4-8-4" configuration or higher. Bacterial invasion of the sulcular epithelium occurred before clinical evidence of NUG could be observed. It is concluded that invasion by intermediate spirochetes and other bacteria plays a role in initiating ulcerative gingivitis in beagles.

Gastric Leiomyomas in the Japanese Newt, Cynops pyrrhogaster; Ultrastructural observations

Nineteen of 700 outwardly healthy captive adult Japanese newts, Cynops pyrrhogaster, had nodular neoplasms protruding on the gastric serosal surface. These tumours were characterized as sharply circumscribed leiomyomas of the muscularis externa with occasional submucosal involvement. Ultrastructural analysis of tumour myocytes revealed irregular-shaped, well-differentiated cells with cytoplasmic processes, and reduced quantities of intracellular myofibrils. They were surrounded by enlarged intercellular spaces filled with disorganized and increased amounts of collagen. Vacuolation was seen both in tumour myocytes and in mucous epithelial cells. Virus-like particles were observed in nuclei of some tumour myocytes. Interstitial cells with laminated-type granules were seen amongst tumour cells. These relatively benign leiomyomas shared some morphologic features with human gastric leiomyomas. Their cause and prognosis remain unknown.