Macroscopic and microscopic characteristics of low grade appendiceal mucinous neoplasms (LAMN) on appendectomy specimens and correlations with pseudomyxoma peritonei development risk.

Low grade appendiceal mucinous neoplasm (LAMN) is the primary source of pseudomyxoma peritonei (PMP). PMP may develop after seemingly complete resection of primary tumor by appendectomy, which is unpredictable due to lack of reliable prognostic indicators. We retrospectively reviewed 154 surgically resected LAMNs to explore if any of the macroscopic and microscopic characteristics may be associated with increasing risk of PMP development. Our major findings include: (1) As compared to those without PMP, the cases that developed PMP were more frequent to have (a) smaller luminal diameter (<1 cm) and thicker wall, separate mucin aggregations, and microscopic perforation/rupture, all suggestive of luminal mucin leakage; (b) microscopic acellular mucin presenting on serosal surface and not being confined to mucosa; and (c) neoplastic epithelium dissecting outward beyond mucosa, however, with similar frequency of neoplastic cells being present in muscularis propria. (2) Involvement of neoplastic cells or/and acellular mucin at surgical margin did not necessarily lead to tumor recurrence or subsequent PMP, and clear margin did not absolutely prevent PMP development. (3) Coexisting diverticulum, resulted from neoplastic or non-neoplastic mucosa being herniated through muscle-lacking vascular hiatus of appendiceal wall, was seen in a quarter of LAMN cases, regardless of PMP. The diverticular portion of tumor involvement was often the weakest point where rupture occurred. In conclusion, proper evaluation of surgical specimens with search for mucin and neoplastic cells on serosa and for microscopic perforation, which are of prognostic significance, should be emphasized.

Suspension culture promotes serosal mesothelial development in human intestinal organoids.

Pluripotent-stem-cell-derived human intestinal organoids (HIOs) model some aspects of intestinal development and disease, but current culture methods do not fully recapitulate the diverse cell types and complex organization of the human intestine and are reliant on 3D extracellular matrix or hydrogel systems, which limit experimental control and translational potential for regenerative medicine. We describe suspension culture as a simple, low-maintenance method for culturing HIOs and for promoting in vitro differentiation of an organized serosal mesothelial layer that is similar to primary human intestinal serosal mesothelium based on single-cell RNA sequencing and histological analysis. Functionally, HIO serosal mesothelium has the capacity to differentiate into smooth-muscle-like cells and exhibits fibrinolytic activity. An inhibitor screen identifies Hedgehog and WNT signaling as regulators of human serosal mesothelial differentiation. Collectively, suspension HIOs represent a three-dimensional model to study the human serosal mesothelium.

The embryonic development of the bovine stomach revisited.

The adult anatomy and physiology of the bovine (Bos taurus) stomach have been investigated extensively. Despite the many studies, however, the early development of the stomach has not yet been fully elucidated. The goal of the present study, therefore, was to review the available literature, to visualize the embryonic and early foetal development of the bovine stomach and to shed light on unresolved issues. The stomachs of fifteen bovine embryos and eleven foetuses from 26 to 80 days of gestation were photographed both in situ and after exenteration and critical point drying. A series of photographs was obtained that yielded a contiguous and comprehensive view of all the developmental changes that occurred until the virtually final configuration of the stomach was attained. In addition, the serosal surface was studied by electron microscopy, thus revealing subtle regional differences in the lining of the peritoneal cavity. Our observations corroborate the contention that all the compartments evolve from the fusiform primordium and that no outgrowth at the level of the oesophagus occurs. The greater curvature as well as the attachment line of the dorsal mesogastrium shift to the left, which is similar to the process in monogastrians. The rumen and reticulum develop from separate protrusions, and further compartmentalization results from constrictions and bulges and not from folding. Between 55 and 60 days of gestation, the entire bovine stomach except for the abomasum eventually relocates to its final position. In summary, previously debated key issues were addressed and integrated with current findings.

Development and ultrastructure of the thickened serosa and serosal cuticle formed beneath the embryo in the stonefly Scopura montana Maruyama, 1987 (Insecta, Plecoptera, Scopuridae).

We aimed to describe the development and ultrastructure of the thickened serosa and serosal cuticle formed beneath the embryo of Plecoptera, using Scopura montana of Scopuridae as a euholognathan representative. Using transmission electron microscopy, we found that the egg membranes were composed of a thick exochorion, a thicker endochorion consisting of two sublayers, and an extremely thin vitelline membrane. The egg membrane construction represents a groundplan feature of the euholognathan egg membranes. The serosa converges beneath the embryo to form a thickened serosa, comprising cells in a radial arrangement, in association with the formation of the amnioserosal fold. The thickened serosa then deposits the thickened serosal cuticle, consisting of four layers differing in fine structure and electron density. After achieving its secretory function, the thickened serosa then disintegrates, and the liberated serosal cells float for a short period in the peripheral region of the egg inside. Collectively, our findings should provide the basis for further characterization of the serosal structures concerned, but we were unable to corroborate previous studies assigning the thickened serosa and serosal cuticle in Plecoptera to the water absorption function.

Serosal membranes (pleura, pericardium, peritoneum). Normal structure, development and experimental pathology.

This monograph offers a comprehensive review of the present knowledge of the structure of the serosal coverings of the pleural, pericardial, and peritoneal cavities in humans and laboratory animals. The authors provide data from their own research--with transmission and scanning electron microscopy--on the structure of the main components of the serosal membranes: mesothelial cells, underlying basal lamina, and submesothelial connective tissue layer. Two main types of mesothelial cells (flat and cubic) are distinguished and their distribution on the parietal serosal sheets and on the visceral coverings of various organs is described. The openings between mesothelial cells (stomata) and their relations with lymphatic lacunae are described thoroughly. Special reference is made to the serosal accumulations of lymphoid tissue (milky spots). The transcellular and intercellular transport to and from serosal cavities is studied by means of horseradish peroxidase tracing experiments. The prenatal and postnatal developmental studies are focused on human and rat pleura. The alterations of serosal membranes after experimental hemothorax, pneumonectomy, and peritonitis caused by Pseudomonas aeruginosa application suggest the existence of early, reversible, and late, definite periods.

Structure and function of the extraembryonic membrane persisting around the larvae of the parasitoid Toxoneuron nigriceps.

The embryo of Toxoneuron nigriceps (Hymenoptera, Braconidae) is surrounded by an extraembryonic membrane, which, at hatching, releases teratocytes and gives rise to a cell layer embedding the body of the 1st instar larva. This cell layer was studied at different developmental times, from soon after hatching up to the first larval moult, in order to elucidate its ultrastructural, immunocytochemical and physiological function. The persisting "larval serosa" shows a striking structural and functional complexity: it is a multifunctional barrier with protective properties, limits the passage of macromolecules and it is actively involved in the enzymatic processing and uptake of nutrients. The reported results emphasizes the important role that the embryo-derived host regulation factors may have in parasitism success in Hymenoptera koinobionts.

Embryonic development of a collembolan, Tomocerus cuspidatus Börner, 1909: with special reference to the development and developmental potential of serosa (Hexapoda: Collembola, Tomoceridae).

The embryogenesis of a collembolan, Tomocerus cuspidatus, was examined and described, with special reference to the development of serosa and its developmental potential. As a result of cleavage, which starts with holoblastic cleavage and changes to the superficial type, the blastoderm forms. At the center of the dorsal side of the egg, the primary dorsal organ develops. The mesoderm is segregated beneath the entire blastoderm, excluding the primary dorsal organ. The mesoderm then migrates to the presumptive embryonic area, and the embryonic and extra-embryonic areas differentiate. The area lined with mesoderm is the embryo, and that devoid of it is the serosa. Owing to blastokinesis completion, the extra-embryonic area or the serosa is highly stretched, and the serosal cells are often found to undergo mitosis. The serosa possesses the ability to differentiate into the body wall. It was confirmed, in contrast to the previous understanding, that the serosal cells do not degenerate, but participate in the formation of the body wall or definitive dorsal closure. Integrating this newly obtained information and other embryological evidence, the basal splitting of Hexapoda was phylogenetically discussed and reconstructed, and a phylogeny formulated as "Ellipura (=Protura+Collembola)+Cercophora (=Diplura and Ectognatha)" was proposed.

Decrease in Cell Volume Generates Contractile Forces Driving Dorsal Closure.

Biological tissues must generate forces to shape organs and achieve proper development. Such forces often result from the contraction of an apical acto-myosin meshwork. Here we describe an alternative mechanism for tissue contraction, based on individual cell volume change. We show that during Drosophila dorsal closure (DC), a wound healing-related process, the contraction of the amnioserosa (AS) is associated with a major reduction of the volume of its cells, triggered by caspase activation at the onset of the apoptotic program of AS cells. Cell volume decrease results in a contractile force that promotes tissue shrinkage. Estimating mechanical tensions with laser dissection and using 3D biophysical modeling, we show that the cell volume decrease acts together with the contraction of the actin cable surrounding the tissue to govern DC kinetics. Our study identifies a mechanism by which tissues generate forces and movements by modulating individual cell volume during development.

Yolk utilization in stick insects entails the release of vitellin polypeptides into the perivitelline fluid.

This study investigates the developmental fate of vitellin (Vt) polypeptides generated by limited proteolysis in an insect embryo. To this end, a number of polyclonal (pAb) and monoclonal antibodies (mAb) were raised against the yolk sac and the perivitelline fluid of late embryos of the stick insect Carausius morosus. Two dimensional immuno gel electrophoresis and Western blotting demonstrate that polypeptides resulting from Vt processing are present both in the yolk sac and the perivitelline fluid. At the confocal microscope, different labelling patterns were detected in the ooplasm depending on the stage of development attained by the embryo. At early developmental stages, label is associated with large unsegmented portions of the fluid ooplasm. During embryonic development, the fluid ooplasm is gradually transformed into yolk granules by intervention of vitellophages. Prior to dorsal closure, the yolk sac is separated from the perivitelline fluid by interposition of serosa cells (the so called serosa membrane). Several mAbs raised against the perivitelline fluid react specifically with this membrane suggesting that the release of Vt polypeptides from the yolk sac occurs by intracellular transit through the serosa cells. By immunocytochemistry, gold label appears associated with the cell surface and a number of vacuoles of the serosa membrane. These data are interpreted as suggesting that Vt polypeptides resulting from limited proteolysis in stick insect embryos are not exhaustively degraded within the yolk sac, but are instead transferred transcytotically to the perivitelline fluid through the serosa membrane.

Reactive and neoplastic serosal tissue. A light-microscopic, ultrastructural, and immunocytochemical study.

Normal and reactive non-neoplastic serosal tissues and a spectrum of serosal neoplasms were studied using light-microscopic, ultrastructural, immunocytochemical, gel electrophoretic, and immunoblot techniques. Normal surface mesothelium expressed both low- and high-molecular-weight cytokeratins, whereas the scattered submesothelial cells were decorated only with antibodies to vimentin. Reactive non-neoplastic subserosal cells, however, coexpressed both low-molecular-weight cytokeratin and vimentin and demonstrated the ability for surface differentiation during which higher-molecular-weight cytokeratins were acquired and vimentin was lost. The authors suggest the term "multipotential subserosal cells," recognizing the unique intermediate filament expression of reactive subserosal cells and the ability for surface differentiation. The intermediate filament expression of the sarcomatoid/desmoplastic mesotheliomas resembled the MSC, whereas epithelial mesotheliomas resembled surface mesothelium. These findings have potential usefulness for diagnostic pathology.

Multiple myeloma of the serosa coat.

We report on a 47-year-old male patient with IgA-kappa plasmacytoma, who 12 months subsequent to diagnosis developed marked ascites. On light and electron microscopy morphologically identical plasma cells with bizarre intracytoplasmatic material were found in the bone marrow, pleural exudate, and ascites fluid. This kind of extramedullary spread is extremely rare and usually resists therapy. The mean survival rate for the 9 patients with malignant plasmacellular ascites whose cases have been documented so far was 2 months. After progression under VCMP regimens our patient has been successfully treated over a period of more than 4 years with i.v. VP16 monotherapy with additional intermittent local administration of methotrexate and systemic poly-chemotherapy according to the VAD scheme.

A scanning and transmission electron microscope study of the human minor salivary glands.

All human minor salivary glands, apart from the posterior deep lingual (von Ebner's) glands which were serous, contained a minor population of seromucous cells that increased from palatine and posterior superficial lingual (Weber's) to labial, anterior lingual (Blandin and Nuhn's) and buccal glands, in that order. Unlike the predominant mucous cells, whose structure was uniform, serous and seromucous cells exhibited, in each gland, peculiar cytological and cytoarchitectural characters.

Serous cutaneous glands in Phyllomedusa hypochondrialis (Anura, Hylidae): secretory patterns during ontogenesis.

Three syncytial gland types (Ia, Ib, and II ) have been described in the skin of larval, juvenile and adult Phyllomedusa hypochondrialis, which share the ultrastructural traits common to the serous secretory units of anuran skin, although each manufactures a peculiar product. Type la secretion consists of dense granules provided with a peculiar substructure, type Ib of vesicles holding a lucent material, type II of lipid deposits. None of the developmental stages investigated showed intermediate features between any of the three cutaneous products, which accumulate in the syncytial cytoplasms of the secretory units following different biosynthetic pathways, consistent with each gland type. These findings confirm previous results on adult specimens of P. hypochondrialis and P. sauvagei and stress the polymorphism of the serous glands in the genus Phyllomedusa. This morphological variability reflects the wide adaptive flexibility of serous glands in anurans.

Development of serous cutaneous glands in Scinax nasica (Anura, Hylidae): patterns of poison biosynthesis and maturation in comparison with larval glands in specimens of other families.

We examined the development of serous (poison) cutaneous glands in larval and juvenile Scinax nasica (Hylidae) at the ultrastructural level. We describe the biosynthesis and maturation of the cutaneous poison in comparison with the corresponding processes in representatives of Discoglossidae, Leptodactylidae, Pelobatidae and Pipidae. Serous biosynthesis in S. nasica starts in discrete adenoblasts and continues in the syncytial secretory unit. Biosynthetic processes involve rough endoplasmic reticulum and the Golgi apparatus, that releases membrane-bounded material, varying from fine grained to flocculent. During the post-Golgian secretory phase, this material undergoes initial maturation, and two products are formed: dense granules and larger vesicles holding a thin substance that will later be structured into a three-dimensional, honeycomb-like net. Both the secretory granules and vesicles change into glomerular-like aggregates of bowed, rod-shaped subunits (modules). In adult frogs, formation of dense granules is bypassed. The modular granule substructure seems to be related to the merocrine release of small amounts of poison, involved in regulating skin homeostasis. Comparison with maturational changes in larval glands of species representing four anuran families discloses similar patterns in the Leptodactylidae, but production of opaque homogeneous granules occurs in the Discoglossidae, clear vesicles in the Pelobatidae and aggregates of dense bars in the Pipidae.

The mesothelial cells in CAPD effluent and their relation to peritonitis incidence.

The total cell count and cell differentiation of the overnight peritoneal dialysis effluent (PDE) was analysed in 34 long-term CAPD patients. The mean percentage and yield of mesothelial cells were 3.1% and 0.17 x 10(6) per PDE. There was a significant lower percentage and yield of mesothelial cells in the PDE of patients with a peritonitis incidence (PI) of more than 2 episodes a year. Independent of dwell time, a positive correlation between the total yield of leucocytes and the yield of mesothelial cells was found. No relation between the amount of phospholipids in the PDE and the yield of mesothelial cells could be shown. Mesothelial cells in the PDE are probably reflecting the turn-over rate of a reactive mesothelium. Whether a low turn-over rate of the mesothelium is causing or is caused by a high PI needs further investigation.

Ultrastructure, distribution, and density of lamellar bodies in human peritoneum.

OBJECTIVE: To determine the ultrastructure, relative density, and location of lamellar bodies in the various regions, structures, cells, and intercellular matrix in normal human peritoneum; to carry out engineering analysis of the role of lamellar structures in serosal lubricancy and deduce what effect this system may have on the process of peritoneal dialysis. DESIGN: Five samples of normal human parietal peritoneum obtained at elective operation were fixed in a tannic acid-glutaraldehyde mixture and submitted to examination by transmission electron microscopy. Detailed analysis using reconstruction of serial electron micrographs and tracings of montages were employed in determining location, disposition, density, and geometric patterns of lamellar bodies in all levels of the peritoneal membrane. RESULTS: Lamellar profiles were found in greatest density enmeshed in surface microvilli and in mesothelial cytoplasm. Lamellar bodies were frequently observed capping the external portion of mesothelial junctional complexes, and within intercellular junctions. Lamellar bodies were also encountered in macrophages, both in the peritoneal cavity and submesothelial tissue, and also in fibroblasts. Lamellar bodies were present in low density in the matrix ground substance of submesothelial connective tissue, in blood vessel walls between smooth muscle, in endothelial cell cytoplasm, and in vascular lumina. CONCLUSION: Three-dimensional analysis of lamellae on mesothelial surfaces indicates that an arrangement of constantly changing microscopic spheres and cylinders would act as "ball and roller bearings" among the microvilli for the lubrication of opposing surfaces. The entrapment of fluid in lamellar bubbles, which in normal peritoneum fill the microvillous layer, would, if maintained in peritoneal dialysis, constitute a stagnant layer of considerable stability and inertia.

Serous and mucous cells of human submandibular salivary gland stimulated in vitro by isoproterenol, carbachol and clozapine: an LM, TEM, and HRSEM Study.

We have investigated by LM, TEM, and HRSEM the effects of D,L-isoproterenol (beta-adrenergic agent), carbachol (muscarinic agent) and clozapine on biopsy specimens of human submandibular gland stimulated in vitro in an inorganic oxygenated medium. Clozapine is a dibenzodiazepine derivative used in psychotic patients that provokes hypersalivation, a displeasing side effect that often causes discontinuance of therapy. Our findings demonstrate that clozapine acts on salivary mucous and seromucous (serous) cells of the gland as a muscarinic agonist. However, the induced secretory response seems to differ qualitatively and quantitatively from that resulting from carbachol. Thus, in agreement with published data resulting from therapeutic treatments and from experimental studies on rats, the mechanism of clozapine induced hypersialorrhea remains open to further investigation.

[Structural and functional characteristics of the cellular reaction of the bladder epithelium in the frog to calcium extraction from the apical and basolateral membranes]. / Strukturno-funktsional'nye osobennosti reaktsii kletok épiteliia mochevogo puzyria liagushki na izvlechenie kal'tsiia iz apikal'noi i bazolateral'noi membran.

Extraction of Ca++ ions from cells of the frog urinary bladder serosa side is followed by an increase in the bladder wall permeability for water and inulin. Ultrastructural changes were observed, such as destruction of cell junctions, swelling of the cell and their organelles, reconstruction of the cytoskeleton elements. The free calcium Ringer solution injected in the bladder lumen does not change the permeability of the wall for water and sodium ions. In this case the cell response to the antidiuretic hormone decreases; the ultrastructure of cells and intercellular junctions is not disturbed; the distribution of intramembrane particles on the P- and E-faces of the apical membrane is normal. The above results indicate that there are qualitative differences in the cell response towards the extraction of Ca++-ions between the serosal and mucosal membranes. This also suggests that on the external surface of the apical membrane Ca++ ions may play a very important role in redistribution of intramembrane particles under the action of the antidiuretic hormone.

[Anatomy and histotopography of human pericardial lymphoid tissue]. / Anatomiia i gistotopografiia limfoidnoi tkani perikarda cheloveka.

Data concerning microscopic structure of the layers of human serous pericardium, localization of lymphoid structures as related to them and their interrelations with connective tissue elements and vessels are represented. Findings on the thickness of serous pericardium in different layers are also given.

[The enzymatic barrier of the small intestine]. / Enzimaticheskii bar'er tonkoi kishki.

The small intestine's barrier functions are reviewed. The data on mechanical (passive) and active protective systems of the organism against various antigens, toxic substances and proteins, is presented. An important role of these protective systems as an enzyme apparatus of epithelial and postepithelial layers of the small intestine's mucose, is shown.