Antitumour necrosis factor-alpha chimeric antibody (infliximab) inhibits activation of skin-homing CD4+ and CD8+ T lymphocytes and impairs dendritic cell function.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and altered differentiation of keratinocytes in reply to cytokines such as interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha, provided by infiltrating CD4+ and CD8+ T cells and natural killer cells. Infliximab is a chimeric monoclonal antibody that neutralizes both soluble and membrane-bound TNF-alpha, and that may give a long-term disease remission. OBJECTIVES: To determine the in vitro effects of infliximab on CD4+ and CD8+ T cells derived from lesional skin, and on dendritic cells (DCs). METHODS: Psoriatic T-cell lines were isolated from lesional skin of four patients with psoriasis and assayed for their proliferation, cytokine release and susceptibility to apoptotic stimuli in the presence of graded (1-100 microg mL(-1)) concentrations of infliximab. DCs were differentiated in the presence of infliximab from peripheral blood monocytes. Phenotype was assessed by fluorescence-activated cell sorting and antigen-presenting capacity in functional assays. RESULTS: In vitro activation of psoriatic as well as antigen (nickel)-specific skin-homing T cells was strongly and dose-dependently impaired by infliximab, in terms both of proliferation and of IFN-gamma release. Despite the significant reduction of IFN-gamma secretion, infliximab only marginally affected the release of interleukin (IL)-10 by skin T cells, thus determining a reduction of the IFN-gamma/IL-10 ratio at the site of inflammation. The effects were maximal when T-cell activation occurred in the absence of costimulation, or when T cells were activated by immature compared with mature DCs. In addition, skin-homing CD8+ T cells were more prominently affected by infliximab compared with CD4+ T lymphocytes, both in terms of inhibition of activation and in their susceptibility to apoptosis. Finally, infliximab directly affected the differentiation of monocyte-derived DCs, by inhibiting the expression of CD1a and CD86, and strongly impaired the antigen-presenting capacity of immature and, to a lesser extent, mature DCs. CONCLUSIONS: Infliximab directly affects psoriatic T cells and impairs the antigen-presenting capacity of DCs. These effects may help to explain the long-term disease remission obtained with the drug.

[Savariaud's maneuver in surgical procedures used for direct hemostasis in gastric hemorrhage]. / La manovra di Savariaud nei procedimenti chirurgici di emostasi diretta per emorragia gastrica.

The paper illustrates the manoeuvre proposed by Savariaud for the surgical exploration of the gastric cavity. The indications and results of the method are described and its considerable diagnostic and therapeutic value are underlined especially in the presence of severe gastric hemorrhage.

[Clamping the suprahepatic inferior vena cava in emergency surgery. Technical note]. / Controllo della vena cava inferiore sovraepatica in urgenza. Note di tecnica chirurgica.

In major hepatic surgery the temporary exclusion of the vena cava may be achieved using a variety of more or less complex procedures. Alternatively, for use above all in emergency surgery, the paper illustrates a method of clamping the suprahepatic inferior vena cava using a left lateral route, which is quick to carry out and undoubtedly efficient.

[Subdiaphragmatic aortic clamping in abdominal hemorrhagic emergencies]. / Clampaggio aortico sottodiaframmatico nelle emergenze emorragiche addominali.

The paper describes a technique of subdiaphragmatic aortic clamping as a provisional method to stop blood flow in abdominal hemorrhage emergencies. The numerous indications for the method and satisfactory results obtained by its use are described.

[Position anomalies of the gallbladder. Apropos of 4 cases]. / Anomalie di posizione della colecisti. A proposito di quattro osservazioni.

Four cases of ectopic gallbladder are reported and interesting pictures presented. Related embryological, diagnostic and therapeutic aspects are then examined.

[Hemoperitoneum in segmental portal hypertension caused by pancreatic pseudocyst]. / Emoperitoneo in corso di ipertensione portale distrettuale da pseudocisti pancreatica.

A case of haemoperitoneum during segmentary portal hypertension due to pancreatic pseudocyst is reported. After a short general review, certain physiopathological and therapeutic aspects of particular practical interest are presented.

Chemoreception in Turbellaria.

This paper reviews the ultrastructural features and the behavioural aspects of presumptive chemoreceptors as reported in the literature, and adds some new observations. The involvement of both uniciliary and multiciliary sensory receptors has been cited. In some cases the expanded membrane area is due to microvillar projections and the ciliary segment is either reduced or absent. The chemoreceptive function can be inferred from comparison with similar, identified chemoreceptors in other taxa, from their specific location on the body surface, or from selective ablation experiments resulting in modified behavioural responses to known stimulants. In addition to feeding and ingestive behaviours, chemosensory cues are used in other ecologically adaptive functions such as habitat selection, intraspecific social communication which modulates reproduction, and several symbiotic relationships. Oriented behaviours can be altered by experience, giving rise to a more efficient colonization of different habitats or to a better exploitation of different food resources. Changes in water quality or the presence of pollutants will influence chemoreceptive abilities and can disrupt adaptive behavioural patterns.

Interaction between photoreceptors and pigment epithelium in developing pigeon retina: an electrophysiological and ultrastructural study.

In pigeons as in other vertebrates, the electroretinogram (ERG) first can be recorded simultaneously with the appearance of the photosensitive lamellae in the developing outer segments. At around 4-6 days after the bird has hatched a small negative-positive complex (a-b-wave) appears. Simultaneously, a c-wave can be recorded and the termination of the stimulus is followed by a positive d-wave. The ERG amplitude progressively increases during the first month as the lamellar structures complete their maturation. The c-wave amplitude shows a steady increase in the early post-hatching period which parallels the a-b complex maturation. In newly hatched pigeons the retinal pigment epithelial (RPE) cell consists of a small soma and long villi which extend toward the photoreceptors. During maturation a progressive increase in RPE thickness and number of cytoplasmic elements can be observed.

Developing pigeon retina: light-evoked responses and ultrastructure of outer segments and synapses.

Morphological development of photoreceptor outer segments and synapses in the foveal region of the pigeon retina was studied by electron microscopy. In addition, the maturation of outer retina function was investigated by recording electroretinographic (ERG) responses to either flash or pattern stimuli. The first ERGs to unpatterned or patterned stimulation can be recorded at 4-6 days posthatching. These results are consistent with anatomical analysis of pigeon photoreceptor and synapse development. Indeed, photosensitive lamellae in the outer segments can be observed simultaneously with the appearance of the first retinal responses to light. A few synapses can already be seen in the outer plexiform layer at the time photoreceptor disks first appear. In contrast, numerous synapses are already present in the inner plexiform layer when photoreceptor lamellae have yet to appear. A comparable maturation pattern has been reported to occur in chicks toward the end of the incubation time.

[4 cases of tricholeukocytic leukemia]. / Osservazioni su 4 casi di leucemia tricoleucocitica.

The clinical, haematological, cytomorphological, cytochemical, ultrastructural, and bone marrow biopsy histological data observed in 4 cases of tricholeukocytic leukaemia are reported, along with some unusual findings. Stress is placed on the varied course of this disease and the difficulties associated with its treatment. Some criteria for the choice of therapy are also proposed.

Ultrastructure of meiosis-inducing (heterotypic) and non-inducing (homotypic) cell unions in conjugation of Blepharisma.

Cells of mating types I and II of Blepharisma japonicum interact with each other and unite in heterotypic (type I-type II) or homotypic (type I-type I, type II-type II) pairs. Heterotypic pairs undergo meiosis and other nuclear changes of conjugation, while homotypic pairs remain united for days without the nuclear changes taking place. We compared cell unions of these two kinds of pairs at the ultrastructural level. In the homotypic union, cell membranes are closely juxtaposed, separated by a distance of about 20 nm. This arrangement is interrupted in some places by vacuoles and small cytoplasmic bridges. Saccule-like structures tend to be more abundant near the united surfaces. Microtubules running at right or slightly obtuse angles with the cell surface (PACM microtubules) are characteristically present at the united region of cells. These structures are very similar to those observed in earlier stages of the heterotypic union. However, in homotypic pairs, cells unite only at the anterior half of the peristome, while in heterotypic pairs cells unite also at the posterior half of the peristome, where the cell membrane totally disappears in later stages. PACM microtubules persist for at least 18 h in homotypic unions, while they disappear within a few hours in heterotypic unions. These differences between the two kinds of cell union are discussed in relation to the initiation mechanism of meiosis and other nuclear changes of conjugation. Similarities between homotypic union and cell junctions in multicellular organisms are also discussed.

Degenerative and regenerative processes in the olfactory system of homing pigeons.

Experimental resection of the olfactory nerve in the homing pigeon induces a total degeneration of the nerve and olfactory epithelium. The orthograde degenerative process starts before the retrograde one. Ten days after resection, new neurons begin to differentiate from the basal cells. The axon forms earlier than the distal dendritic process, and the speed of growth increases slowly. The regenerated axons only reach the bulb in the 5th month. Two months after resection the olfactory epithelium is similar to that of the intact control side. The ultrastructural features of the mucosa and olfactory axons are similar to those of normal ones.

Olfactory nerve reconstitution in the homing pigeon after resection: ultrastructural and electrophysiological data.

Homing pigeons were subjected to uni- or bilateral resection of the olfactory nerves. A control of the operated region carried out five months later, showed that the olfactory nerves were continuous from the olfactory mucosa to the bulb. Cross sections of the regenerated nerve, observed under the electron microscope, showed morphological alterations with respect to the normal. Total measurement of the cross surface of both olfactory nerves showed that the regenerated nerve is always smaller than the intact nerve; this is also apparent in the total number of the fibres counted. Electrophysiological tests, performed on the regenerated nerve showed that the conduction along the resected nerve is restored.

Fine structural observations on the ciliary receptors in the epidermis of three otoplanid species (Turbellaria proseriata).

In Notocaryoturbella bigermaria, Otoplana truncaspina and Paroto-planella heterorhabditica three types of epidermal receptors are recognized. Type I: with a single cilium running in a duct, piercing the distal dendrite process of the receptor. The internal wall of the dendrite process has eight ridges with longitudinal filaments lying inside them. The ciliary basal body lacks a longitudinal rootlet but is encircled by a thin annular formation. Type II: with a single (A) or several (B) cilia which protrude from the outer epithelial surface and are provided with a large and striped rootlet. Both types are considered as mechanoreceptors. Type III: with two or more short and stumpy cilia devoid of rootlets and displaying the usual 9 + 2 pattern in the proximal part only. They are considered as chemoreceptors.