Evolution and integration of innate immune systems from fruit flies to man: lessons and questions

Despite broad differences in morphology, ecology and behavior, the fruit fly Drosophila melanogaster and humans show a remarkably high degree of conservation for many molecular, cellular, and developmental aspects of their biology. During the last decade, similarities have also been discovered in some of the mechanisms regulating their innate immune system. These parallels regard mainly the Toll-like receptor family and the intracellular signaling pathways involved in the control of the immune response. However, if the overall similarities are important, the detailed pathogen recognition mechanisms differ significantly between fly and humans, highlighting a complicated evolutionary history of the metazoan innate defenses. In this review, we will discuss the main similarities and differences between the two types of organisms. We hope that this current knowledge will be used as a starting point for a more comprehensive view of innate immunity within the broad variety of metazoan phyla.     

Type III a glycogenosis

Summary A combined biochemical and ultrastructural study, including cytochemical and negative staining techniques, has been made of three tissues, liver, muscle and leucocytes, in a case of type III A glycogenosis.The electron microscopic studies revealed an increased accumulation of glycogen in the liver, in the skeletal muscle and in the leucocytes.The hepatic glycogen, either isolated or within the hepatocytes, is mostly represented in the form of monoparticulate granules and of rosettes with fewer component units, whereas the typical rosettes are rare. The isolated and intracellular glycogen of muscle cells appears composed of monoparticulate granules, as in normal muscle cells.The biochemical studies confirm the diagnosis of type III A glycogenosis and seem to exclude the simultaneous occurrence of the enzymatic defect responsible for type II glycogenosis.

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Typ III A GlykogenoseEine biochemische und ultrastrukturelle Untersuchung

Zusammenfassung Die Beobachtung einer Glykogenose (Typus III A) bei einem 11 Jahre alten Jungen wurde biochemisch, elektronenmikroskopisch, cytotopochemisch und durch eine Reihe sog. Negativfärbungen durchgearbeitet. In Leber, Muskulatur und Leukocyten wurden starke Glykogenanhäufungen nachgewiesen. Das Leberglykogen war, sowohl in Schnittpräparaten als auch bei isolierter Untersuchung, von dem normalen Glykogen des gesunden Menschen deutlich verschieden. Sogenannte typische Rosetten wurden nur ganz ausnahmsweise gefunden. Dagegen fanden sich sog. kleine Rosetten, jeweils zusammengesetzt aus einigen wenigen Partikeln, vor allem aber monopartikuläre Granula. In der Muskulatur jedoch trat das Glykogen, wie auch beim gesunden Menschen, monopartikulär und granuliert auf.Biochemisch konnte die Diagnose einer Glykogenose des Typus III A eindeutig gestellt werden. Es haben sich keine Anzeichen dafür nachweisen lassen, daß ein sog. Fermentdefekt, etwa wie bei einer Glykogenose des Typus II, zugrunde lag.

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This work was supported by Grant N. 115/815/1270 from the Consiglio Nazionale delle Ricerche, Comitato Biologia e Medicina. Italy.

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Dr.Minio Paluello and Dr.Bruni are fellows of Consiglio Nazionale delle Ricerche.     

Distant muscular (gluteus maximus muscle) metastasis from laryngeal squamous cell carcinoma

Clinical evidence of non-lymphatic distant metastasis has been reported in approximately 10% of cases of head and neck squamous cell carcinoma (HNSCC). The lungs are the commonest site of distant metastasis of HNSCC, followed by the bones, liver and skin. A 65-year-old male underwent supraglottic laryngectomy and left modified neck dissection for a carcinoma of the laryngeal surface of the epiglottis extending to both false cords. Eight months later the patient underwent right radical modified neck dissection for hypodermal metastatic disease involving the underlying (sternocleidomastoid) muscle. Thirty-two months later, surgical excision of a lesion in the right gluteus maximus muscle was performed. Histological study diagnosed a muscular metastasis with the same morphological aspect as the laryngeal carcinoma. The patient showed no evidence of cervical or distant recurrence at follow-up after 13 months. Although skeletal muscles represent approximately 50% of total body mass and receive a large proportion of total cardiac output, haematogenous metastases to skeletal muscle are extremely uncommon. Most skeletal muscle metastases are of pulmonary origin. Distant skeletal muscle metastasis from HNSCC is an extremely rare occurrence. Treatment options, depending upon the clinical setting, include observation, radiotherapy, chemotherapy and excision; these approaches rarely alter the patient outcome. The prognosis associated with skeletal muscle metastasis is thought to be poor, consistent with the fact that it generally occurs as a feature of systemic spread.     

Localization and quantification of fluorescent inclusions embedded in a turbid medium

A set-up, based on a CCD camera, to localize fluorescent inclusions in diffusing media was developed. This set-up allows one to acquire a huge dataset along two axes. This aspect is fundamental to performing a tomographic reconstruction in order to quantify the fluorescence amplitude in each voxel of the sample. Firstly, a simple analytical approach to recover the position of a single inclusion, embedded in a turbid medium, was developed. Then, we implemented a reconstruction algorithm to recover the position of one and two inclusions and to estimate their relative concentrations. Finally, we studied the dependence of reconstructed data on the number of injection points of excitation light and the number of detection points of fluorescence emission.     

Human cortical responses during one-bit delayed-response tasks: an fMRI study

Neuroimaging study of cognition across aging requires simple tasks ensuring: (i) high rate of correct performances in neurophysiological settings; and (ii) significant modulation of cortical activity. As a preliminary step, the present functional magnetic resonance imaging (fMRI) study tested the hypothesis that very simple delayed-response tasks fit these requirements in normal young adults. The short-term memory (STM) variant included a sequence of cue stimulus (two vertical bars), delay period (blank screen for only 5s), go stimulus, and motor response compatible with the taller vertical bar. Noteworthy, the retention (only one bit) could be based on visuo-spatial, phonological, and somatomotor coding. In the control variant (no STM, NSTM), the cue stimulus was present during the delay period. Results showed high rate of correct performances in both tasks (about 95%). Compared to the NSTM task (delay period), the STM task enhanced cortical responses in bilateral dorsolateral prefrontal (Brodmann area 8-9 (BA 8-9)), lateral premotor (BA 6L), medial premotor (BA 6M), inferior parietal (BA 40), and superior parietal (BA 7) areas. In the STM task, cortical responses were stronger in right than left BA 8-9 and BA 6L. These results indicate that, in normal young adults, a simple STM variant of delayed-response tasks (one bit to be retained) is correctly performed and enhances bilateral fronto-parietal responses. Therefore, it may be used for future cognitive neuroimaging studies on aging.     

Functional topography of the secondary somatosensory cortex for nonpainful and painful stimulation of median and tibial nerve: an fMRI study

Functional magnetic resonance imaging (fMRI) was used to study the cortical activity of the bilateral secondary somatosensory cortex (SII) during nonpainful (motor threshold) and painful electrical stimulation of median and tibial nerves. fMRI recordings were performed in eight normal young adults. The aim was at evaluating the working hypothesis of a spatial segregation of nonpainful and painful populations not only in the "hand" representation of SII [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for nonpainful and painful stimuli: an fMRI study. NeuroImage 20, 1625-1638.] but also in its "foot" representation. Results showed that, in both "hand" and "foot" representations of bilateral SII, the activity elicited by the painful stimulation was localized more posteriorly with respect to that elicited by the nonpainful stimulation. A fine spatial analysis of the SII responses revealed a clear somatotopic organization in the bilateral SII subregion especially reactive to the nonpainful stimuli (i.e., segregation of the hand and foot representations). In contrast, it was not possible to disentangle the "hand" and "foot" representations of SII for painful stimuli. These results extended to the SII "foot" representation previous evidence of a spatial segregation in the SII "hand" representation of subregions for the painful and nonpainful stimuli. Furthermore, they suggest that noxious information is not somatotopically represented in human bilateral SII, at least as inferred from fMRI data at 1.5 T.