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Interleukin-15 (IL-15) is a potent regulator of T-, B-, and natural killer cell proliferation and displays unusually tight controls of secretion. Even though IL-15 mRNA is constitutively expressed in monocytes/macrophages and is upregulated by a variety of stimuli, evidence for IL-15 cytokine secretion is only found exceptionally, eg, conditions of pathological, chronic inflammation. This raises the possibility that monocytes express membrane-bound IL-15 rather than secrete it. The current study explores this hypothesis. We demonstrate here that biologically active IL-15 is indeed detectable in a constitutively expressed, membrane-bound form on normal human monocytes, as well as on monocytic cell lines (MONO-MAC-6, THP-1, and U937), but not on human T or B cells (MT4, M9, C5966, JURKAT, DAUDI, RAJI, and Epstein-Barr virus-immortalized B-cell clones). Furthermore, cell surface-bound IL-15 is upregulated upon interferon-gamma stimulation. Interestingly, monocyte/macrophage inhibitory cytokines such as IL-4 and IL-13 fail to downregulate both constitutive and induced cell-surface expression of IL-15. Membrane-bound IL-15 does not elute with acetate buffer or trypsin treatment, suggesting that it is an integral membrane protein and that it is not associated with the IL-15 receptor complex. Finally, membrane-bound IL-15 stimulates T lymphocytes to proliferate in vitro, indicating that it is biologically active. These findings enlist IL-15 in the fairly small family of cytokines for which the presence of a biologically active membrane-bound form has been demonstrated (eg, IL-1, tumor necrosis factor-alpha, and IL-10) and invites the speculation that most of the biological effects of IL-15 under physiological conditions are exerted by the cell surface-bound form.

The existing registries of thyroid carcinoma are seldom comparable as far as epidemiological data, diagnostic criteria and histopatological description are concerned. Epidemiological studies report a progressive increase in the incidence of thyroid carcinoma in the last twenty years and in both sexes this increase of incidence has been referred to papillary histotype. Data collected from surgical series show a rate of thyroid carcinomas from 7 to 20% of total thyroid surgeries. The present study was designed in order to obtain a retrospective review of the distribution of thyroid carcinoma's different histotypes in the last 21 years in a major General Hospital. Detailed analysis of patients with histologically confirmed thyroid carcinoma admitted between 1974 and 1994 to the Surgery Department of Mauriziano Hospital of Torino, Italy showed an overall 11.8% prevalence of thyroid cancer out of the total thyroid surgeries. The rate of papillary carcinoma was the highest (54.3%) followed by follicular carcinoma (27.6%), anaplastic carcinoma (11.1%), medullary carcinoma (4.6%) and others (2.4%). The papillary-to-follicular ratio varied from 0.60 in 1974-76 to 6.88 in 1992-94. Female to male ratio of all thyroid carcinoma histotypes was 2.0 or more; papillary and follicular histotypes had the highest ratio. The variations of the histotype rate observed may be consequence of the silent increase of daily iodine intake throughout the subsequent years, while improved diagnostic tools available and increased experience of the medical staff have probably increased the number on thyroid ablations performed. Our data confirm the changing epidemiology of thyroid carcinoma, reported by international literature.

The author describe a rare case of pancreatic beta-cell hyperplasia. The patient was referred to us because of serious hypoglycemic crises. During hospitalization, endogenous hyperinsulinism was confirmed by hematochemical and instrumental tests. AngioCT of the pancreas evidenced a small lesion of the corpus, suspected of insulinoma. The patient underwent a corpus caudalis pancreatectomy: a small nodule with histologic neuroendocrine traits was ablated. A few days after the operation, new symptomatic hypoglycemia appeared. The hormonal tests confirmed a recurrence of endogenous hyperinsulinism. The patient underwent a new operation for pancreaticoduodenectomy: histological examination confirmed a pancreatic beta-cells hyperplasia. This condition has to be taken into account in the differential diagnosis of post prandial hypoglycemia. Besides, the observation of an insulinoma doesn't exclude the presence of a diffused disorder of islet cells as in the case above described.

Cytogenetic investigation on short-term cultures of 13 nasal polyps disclosed the presence of chromosome aberrations in three cases: one (a recurrence) showed numerical changes; the other two had structural abnormalities, an inv(12)(g15g22) in one case, a der(6)t(6;12)(g22;ql5) in the other. The three cases were characterized histologically by the presence of frequent atypical stromal cells, and were positive for vimentin and smooth muscle actin. Of the remaining 10 cases, three were not analyzable, and seven had normal karyotypes, although random structural changes were seen in two of them.

Wegener's granulomatosis (WG) is a rare small vessels necrotizing and granulomatous systemic vasculitis which usually affects the respiratory-tract and the kidneys. Diagnosis is often difficult, but has become easier with antineutrophil cytoplasmic antibodies (ANCA) detection that may justify a more aggressive biopsy policy also in the elderly. Classic treatment with steroids and oral cyclophosphamide (CY) has proven to be of benefit, but side-effects are severe and frequent and the search for less toxic therapeutic schemes should be encouraged. We treated with intravenous pulses of CY (1 g/m2 monthly for 6 months, every two months for the following 6 and quarterly for another year) 5 of 7 patients with WG recently admitted to our institution. We obtained a quick, complete response in 4 of these patients, with no side effects, nor relapses, after a mean follow-up of 17 months. The only patient who did not respond was identified soon after the beginning of the treatment because of a poor reduction of ESR and could be shifted to oral administration of CY successfully. From our still limited experience CY intravenous pulses have proven to be safe and effective enough to advice its use as the first-choice treatment for WG.

Renal damage is not uncommon in rheumatoid arthritis, but the causative role of the disease per se is not well defined yet. In this paper the updated literature data are reported and our own experience as well. In particular, we describe renal syndromes associated with non-steroidal antiinflammatory drugs, remission-inducing agents (gold and penicillamine) and cytotoxic drugs, secondary amyloidosis, systemic rheumatoid vasculitis, glomerular and tubulo-interstitial nephritis not related to drug therapy.

We report the results of the combined use of surgery and radiation therapy in the treatment of endometrial carcinoma. From January 1974 to December 1989, 89 cases were treated by means of abdominal hysterectomy followed by external radiation therapy. Actuarial survival at 5 years is 100% for stage I, 75% for stage II, and 42.86% for stage III; stage IV patients could not be evaluated. Prognostic factors were statistically significant. In stages II and III survival rates were directly related to histological grading (G1: 90.91%; G2: 81.82%; G3: 25%) and to myometrial infiltration (M1: 85.71%; M2: 81.82%; M3: 70%). Generally, survival was related to age, and prognosis was better in younger patients (under 55) and depended on lymph nodal involvement (N-: 88.24%, versus N+: 25%). Vaginal and pelvic recurrences were 8 (10.1%), and deaths were 13. The identification of high-risk patients will make it possible to select an even more adequate treatment.

Lymphoepithelioma is a particular form of undifferentiated carcinoma, characterized by a prominent lymphoid stroma, originally described in the nasopharynx. Lymphoid stroma-rich carcinomas arising in other organs have been termed lymphoepithelioma-like carcinoma (LELC). In the liver, primary LELCs are very rare, and the majority has been identified as cholangiocarcinomas. Here a rare case of lymphoepithelioma-like hepatocellular carcinoma (HCC) is described. A 47-year old woman presented with abdominal pain. Ultrasonography revealed a liver nodule, 2.2 cm in diameter, localized in the right lobe, adjacent to the gallbladder. Viral markers for hepatic B virus (HBV), hepatic C virus (HCV) and Epstein-Barr virus (EBV) were negative. The nodule was hypoechogenic. The patient underwent surgery, with resection of the nodule. Histology showed hepatocellular carcinoma, characterized by a prominent lymphoid infiltrate. At immunocytochemistry, tumor cells were reactive for Hep Par1 and glypican 3. Immunophenotyping of tumor infiltrating lymphocytes evidenced the predominance of CD8+ cytotoxic suppressor T cells. The postoperative clinical outcome was favorable and the patient was recurrence-free 15 mo after resection. This case, to the best of our knowledge, is the first reported non EBV and non cirrhosis-associated lymphoepithelioma-like hepatocellular carcinoma. The association between the lack of EBV infection, the absence of cirrhosis, a “cytotoxic profile” of the inflammatory infiltrate and a good prognosis could identify a variant of lymphoepithelioma-like HCC with a favorable clinical outcome.

This study aimed to describe a case in which an isolated splenic metastasis was synchronous with the colonic primary and a concomitant splenic abscess was associated. A wide review of the literature was also performed. A 54-year-old woman with abdominal pain and fever was admitted to our department. Abdominal CT revealed two low-density areas in the spleen and wall-thickening of the left colonic flexure, which was indistinguishable from the spleen parenchyma. The patient underwent emergency celiotomy, with the presumptive diagnosis of obstructing colon carcinoma of the splenic flexure, and concomitant splenic abscess. Subtotal colectomy and splenectomy were performed. Pathological findings were consistent with mucinous colonic carcinoma, synchronous isolated splenic metastasis and concomitant splenic abscess. This paper is also a review of the existing literature on the association between colorectal cancer and splenic metastasis. Only 41 cases of isolated splenic metastasis from colon carcinoma have been reported in the literature. This report is the third described case of synchronous isolated splenic metastasis from colon carcinoma. Only one case with concomitant splenic abscess has been previously reported. When obstructing left-sided colorectal cancer is suspected, careful CT examination can allow early diagnosis of splenic involvement by the tumor. The literature review suggests that there might be a significant improvement in survival following splenectomy for a metachronous isolated splenic metastasis from colon carcinoma. Prognosis for synchronous splenic metastasis seems to be related to the advanced stage of the disease. Nevertheless, no definitive conclusions can be drawn because of the small number of cases.

Some immune aspects of simple endemic goiter have been studied through a comparison of IgG, IgA, IgM, k and λ chains, and C3 and C4 in the peripheral blood of 59 patients operated on for goiter and the peripheral blood of 49 normal controls. The median IgM was lower in the goiter blood. The incidence of thyroglobulin (Tg) and microsomal (Mi) antibodies (Abs) was 20.3% in goiter blood and that of nonthyroid autoAbs was 37%. Active and total rosetted blood lymphocytes were counted and OKT3, OKT4, OKT8. Leu 1, Leu3a, Leu2b, T DR+, and NK cell populations were classified. Helper T cells were occasionally decreased when goiter was associated with lymphocytic thyroiditis. The NK percentage was sometimes higher in goiter blood, whereas the T DR+ percentage was not significantly different in the two groups. Lymphocyte infiltration (LI) was noted in 32% of goiters (about 5% with a diffuse and nodular pattern). A prevalence of helper/inducer cells was observed among the infiltrating T cells. HLA-DR antigen (Ag) positive epithelial cells were seen, not only in LI areas. Granular deposits of IgG, IgA, IgM, and C3 on the follicular basal membrane were stained in 6.7% of goiters Patterns histologically and immunologically similar to those in Hashimoto's thyroiditis may therefore be observed in long-standing simple endemic goiter, suggesting that an autoimmune mechanism may be involved in its pathogenesis.

The aim of this research was to study immune aspects of endemic goiter and throw light on the uncertain boundaries between autoimmune and non-autoimmune thyroid diseases.

Patients with thyroid diseases from areas of endemic goitre in Northern Italy were examined for thyroid antibodies by passive haemoagglutination. Of 40 schoolboys with goitre only one had thyroid antibodies (AT) in the blood. Among 182 adults with grade 1-2 goitre, examined within an area of low endemia, the frequency of AT was 7%, not significantly different from that found in the 286 persons with thyroid 'O' living in the same area. Among 181 adults with grade 2-3 goitre, examined within an area of serious endemia, the frequency of AT was 16%; the percentage went up to 24% in 144 patients operated on for goitre. AT frequency was 36% in 87 patients with toxic goitre, more than 70% in 97 patients with Graves' disease and 17% in 60 patients with cancer of the thyroid. AT occurred three times more frequently in women than in men. Microsomal antibodies were more frequently detected than anti-thyroglobulin antibodies: the opposite was true in thyroid cancer. Lymphocytic infiltration (IL) of the gland was observed in 45% of the 464 simple goitres and in 52% of the 60 cancers of the thyroid: it was more frequent and intense in women. Among the 144 patients operated on for goitre the frequency and the titre of AT progressed in parallel with the intensity of the lymphocytic infiltration. Patients with a greater lymphocytic infiltration and higher AT had a higher TSH. Multinodular non-toxic goitre and autoimmune lymphocytic thyroiditis can be present in the same thyroid gland and the clinical expression will depend on which condition predominates.

In recent years, evidence is growing on the role played by gestational factors in shaping brain development and on the influence of intrauterine experiences on later development of neurodegenerative diseases including Parkinson's (PD) and Alzheimer's disease (AD). The nine months of intrauterine development and the first three years of postnatal life are appearing to be extremely critical for making connections among neurons and among neuronal and glial cells that will shape a lifetime of experience. Here, the multiple epigenetic factors acting during gestation - including maternal diet, malnutrition, stress, hypertension, maternal diabetes, fetal hypoxia, prematurity, low birth weight, prenatal infection, intrauterine growth restriction, drugs administered to the mother or to the baby - are reported, and their ability to modulate brain development, resulting in interindividual variability in the total neuronal and glial burden at birth is discussed. Data from recent literature suggest that prevention of neurodegeneration should be identified as the one method to halt the diffusion of neurodegenerative diseases. The "two hits" hypothesis, first introduced for PD and successfully applied to AD and other neurodegenerative human pathologies, should focus our attention on a peculiar period of our life: the intrauterine and perinatal periods. The first hit to our nervous system occurs early in life, determining a PD or AD imprinting to our brain that will condition our resistance or, alternatively, our susceptibility to develop a neurodegenerative disease later in life. In conclusion, how early life events contribute to late-life development of adult neurodegenerative diseases, including PD and AD, is emerging as a new fascinating research focus. This assumption implies that research on prevention of neurodegenerative diseases should center on events taking place early in life, during gestation and in the perinatal periods, thus presenting a new challenge to perinatologists: the prevention of neurodegenerative human diseases.

Interleukin-15 (IL-15) is a potent regulator of T-, B-, and natural killer cell proliferation and displays unusually tight controls of secretion. Even though IL-15 mRNA is constitutively expressed in monocytes/macrophages and is upregulated by a variety of stimuli, evidence for IL-15 cytokine secretion is only found exceptionally, eg, conditions of pathological, chronic inflammation. This raises the possibility that monocytes express membrane-bound IL-15 rather than secrete it. The current study explores this hypothesis. We demonstrate here that biologically active IL-15 is indeed detectable in a constitutively expressed, membrane-bound form on normal human monocytes, as well as on monocytic cell lines (MONO-MAC-6, THP-1, and U937), but not on human T or B cells (MT4, M9, C5966, JURKAT, DAUDI, RAJI, and Epstein-Barr virus-immortalized B-cell clones). Furthermore, cell surface-bound IL-15 is upregulated upon interferon-γ stimulation. Interestingly, monocyte/macrophage inhibitory cytokines such as IL-4 and IL-13 fail to downregulate both constitutive and induced cell-surface expression of IL-15. Membrane-bound IL-15 does not elute with acetate buffer or trypsin treatment, suggesting that it is an integral membrane protein and that it is not associated with the IL-15 receptor complex. Finally, membrane-bound IL-15 stimulates T lymphocytes to proliferate in vitro, indicating that it is biologically active. These findings enlist IL-15 in the fairly small family of cytokines for which the presence of a biologically active membrane-bound form has been demonstrated (eg, IL-1, tumor necrosis factor-, and IL-10) and invites the speculation that most of the biological effects of IL-15 under physiological conditions are exerted by the cell surface-bound form.

The aim of this retrospective study was to assess whether the intratumoral microvessel density (IMD) in primary tumour specimens had any impact on the clinical outcome of patients with advanced epithelial ovarian cancer treated in two Italian departments of gynaecological oncology.The study was conducted on 101 patients who underwent initial surgery followed by platinum-based chemotherapy (37) or paclitaxel/platinum-based chemotherapy (64) for International Federation of Gynecology and Obstetrics (FIGO) stage III-IV epithelial ovarian cancer. The median follow-up of survivors from initial surgery was 65 months (range, 27 to 132 months). Paraffin-embedded sections of primary tumour specimens were analysed for IMD by immunohistochemistry using anti-CD34 antibodies.Progression-free survival and overall survival were significantly better in patients with IMDor =40 microvessels/field compared with those with lower IMD (p = 0.0105 and p = 0.0065, respectively). Cox model showed that IMD was the strongest independent prognostic variable for both progression-free survival (p = 0.0267) and overall survival (p = 0.0189).An elevated IMD was associated with a significantly better progression-free survival and overall survival in patients with stage III-IV epithelial ovarian cancer who underwent initial surgery followed by chemotherapy, mainly consisting of a paclitaxel/platinum-based regimen.