Necrotizing fasciitis in haematological patients: a different scenario.

To describe and compare the characteristics of necrotizing fasciitis (NF) in patients with and without haematological malignancy. All adult patients diagnosed with NF and treated at our hospital were included (January 2010-March 2019). Diagnosis was based on intraoperative findings or consistent clinical/radiological characteristics, and patients were classified as group A (with haematological malignancy) or group B (without haematological malignancy). Student's t (quantitative), Fisher's exact (qualitative), and Kaplan-Meyer tests were used for the statistical analysis. The study included 29 patients: 8 in group A and 21 in group B. All haematological patients had severe neutropenia (0.2 [0.02-0.5] ×109 cells/L; p < 0.001) and positive blood cultures (100% vs. 61.9%; p = 0.04) at diagnosis. Gram-negative bacilli NF was more common in group A (87.5% vs. 9.5%; p = 0.001), predominantly due to Escherichia coli (50% vs. 9.5%; p = 0.056). Surgical treatment was less common in haematological patients (5 [62.5%] vs. 21 [100%]; p = 0.015). Overall, 9 (31%) patients died: 4 (50%) in group A and 5 (23.8%) in group B (p = 0.17). The univariate analysis showed that mortality tended to be higher (OR 3.2; 95%CI 0.57-17.7; p = 0.17) and to occur earlier (2.2 ± 2.6 vs. 14.2 ± 19.9 days; p = 0.13) in haematological patients. The LRINEC index > 6 did not predict mortality in either group. In our study, NF in patients with haematological malignancies was mainly due to Gram-negative bacilli, associated to high and early mortality rates. In our experience, the LRINEC scale was not useful for predicting mortality.

Estudio de la actividad antimicrobiana de una crema dental en gel con EDS frente a Streptococcus mutans y Actinobacillus actinomycetemcomitans / A study of the antimicrobial activity of a EDS-containing dental gel against Streptococcus mutans and Actinobacillus actinomycetemcomitans

Determinar la actividad antimicrobiana de la pasta en gel de dientes contra dos microorganismos: mutans Streptococccus y Actinobacillus actinomycetemcomitans...

Taxonomy of rare genetic metabolic bone disorders.

UNLABELLED: This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. INTRODUCTION: Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. METHODS: IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. RESULTS: This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. CONCLUSIONS: This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

Proline modulates the effect of bisphosphonate on calcium levels and adenosine triphosphate production in cell lines derived from bovine Echinococcus granulosus protoscoleces.

Bisphosphonates have been proposed as pharmacological agents against parasite and cancer cell growth. The effect of these compounds on helminthic cell viability and acellular compartment morphology, however, has not yet been studied. The effects of different types of bisphosphonates, namely etidronate (EHDP), pamidronate (APD), alendronate (ABP), ibandronate (IB) and olpadronate (OPD), and their interaction with amiloride, 1,25-dihydroxycholecalciferol (D3) and proline were evaluated on a cell line derived from bovine Echinococcus granulousus protoscoleces (EGPE) that forms cystic colonies in agarose. The EGPE cell line allowed testing the effect of bisphosphonates alone and in association with other compounds that could modulate calcium apposition/deposition, and were useful in measuring the impact of these compounds on cell growth, cystic colony formation and calcium storage. Decreased cell growth and cystic colony formation were found with EHDP, IB and OPD, and increased calcium storage with EHDP only. Calcium storage in EGPE cells appeared to be sensitive to the effect of amiloride, D3 and proline. Proline decreased calcium storage and increased colony formation. Changes in calcium storage may be associated with degenerative changes of the cysts, as shown in the in vitro colony model and linked to an adenosine triphosphate (ATP) decrease. In conclusion, bisphosphonates could be suitable tempering drugs to treat cestode infections.

Incidence of AIDS-defining cancers and virus-related and non-virus-related non-AIDS-defining cancers among HIV-infected patients compared with the general population in a large health district of Northern Italy, 1999-2009.

OBJECTIVES: The aim of the study was to investigate the incidence of AIDS-defining cancers (ADCs) and virus-related and non-virus-related non-AIDS-defining cancers (NADCs) in HIV-infected patients compared with the general population, and to assess the risk factors associated with these malignancies. METHODS: We performed a retrospective cohort study for the period from 1999 to 2009 of HIV-infected patients residing in the Local Health Authority of Brescia (northern Italy). Observed cancers in patients with HIV infection were compared with expected cancers in the population living in the same area using standardized incidence ratios (SIRs). Risk factors were assessed using Poisson regression analysis. RESULTS: A total of 5090 HIV-infected patients were included in the study, with 32 390 person-years of follow-up. We recorded 416 tumours in 390 HIV-infected patients. Two hundred of these (48.1%) were ADCs, 138 (33.2%) were non-virus-related NADCs and 78 (18.7%) were virus-related NADCs. An increased risk (SIR = 4.2) of cancers overall was found in HIV-infected patients. A large excess of ADCs (SIR = 31.0) and virus-related NADCs (SIR = 12.3) was observed in HIV-infected patients, while the excess risk for non-virus-related NADCs was small (SIR = 1.6). The highest SIRs were observed for Kaposi sarcoma among ADCs and for Hodgkin lymphoma among virus-related NADCs. Conversely, among non-virus-related NADCs, SIRs for a broad range of malignancies were close to unity. In multivariate analysis, increasing age and CD4 cell count < 50 cells/µL were the only factors independently associated with all cancers. CONCLUSIONS: Among HIV-infected people there was an excess of ADCs and also of NADCs, particularly those related to viral infections. Ageing and severe immunodeficiency were the strongest predictors.

Lung cancer in HIV-infected patients: the experience in Brescia from 1999 to 2009.

Lung cancer (LC) is the most common cancer among the non AIDS-defining malignancies in the highly active antiretroviral therapy (HAART) era. We described 23 HIV infected patients with a LC diagnosis followed in the Clinic of Tropical and Infectious Diseases of Brescia during the period of 1999-2009. All of these patients except two (n = 21, 91.3%) were cigarette smokers and all had at least one risk factor for developing cancer of the lung, or predisposing comorbidities, such as a COPD (chronic obstructive pulmonary disease) or a previous pneumonia. The median age at LC diagnosis was 53.6 years (range 21.2-71.4 years). Adenocarcinoma and squamous cell carcinoma were diagnosed in 10 cases (43.5%) respectively. In 21 subjects (91.3%) cancer was detected at stage IV with metastases. The median survival was 5.95 months. Greater intervention focused on the cessation of smoking is necessary, as well as the implementation of closer screening policies, especially in HIV-positive subjects with LC risk factors.

CD29 expressed on plasma cells is activated by divalent cations and soluble CD106 contained in the bone marrow plasma: refractory activation is associated with enhanced proliferation and exit of clonal plasma cells to circulation in multiple myeloma patients.

Malignant plasma cells (PC) in human multiple myeloma (MM) are retained in the bone marrow (BM) microenvironment. Using HUTS21 monoclonal antibody that reacts with active CD29 integrin, we demonstrate that this active form is tightly regulated by divalent cations and soluble CD106 (sCD106) contained in the BM plasma. Moreover, we also show that in vivo expression of the active CD29 on PC was clearly diminished in a minority of MM cases (HUTS21(-) patients). HUTS21(-) cells were refractory to the addition of either normal allogeneic BM plasma or optimal concentrations of exogenous divalent cations and recombinant sCD106. Furthermore, a lower binding to fibronectin was detected in comparison with HUTS21(+) PC. On the other hand, although HUTS21(-) PC showed a reduced amount of total (active+inactive) CD29, western-blot assays demonstrated that these clonal PC contained the two species of CD29, with molecular masses of 110 and 130 kDa, which were expressed on normal or HUTS21(+) PC. Finally, we detected a clear association between the presence of HUTS21(-) PC in the BM and an increased percentage of circulating PC with a high proliferative index, emphasizing the essential role of CD29 in the pathogenesis and progression of this disease.

The evolving burden of HIV infection compared with other chronic diseases in northern Italy.

OBJECTIVES: The aim of the study was to estimate the burden and direct costs of diseases in HIV-infected patients (either opportunistic illnesses or other chronic diseases) with respect to the HIV-uninfected population. These estimates will be useful for the projection of future direct costs of HIV care. PATIENTS AND METHODS: A population-based study was conducted in the Brescia Local Health Agency in northern Italy. An administrative database recorded diagnoses, deaths, drug prescriptions and health resource utilization for all medical and surgical patients in the region from 2003 to 2007. The study estimated the prevalence of HIV infection as well as HIV-related mortality and annual cost per patient, and compared mortality and costs related to HIV infection with those for a set of 15 other chronic diseases. The standardized hazard ratio (SHR) and standardized mortality ratio (SMR) were obtained using an indirect standardization method. RESULTS: The prevalence of HIV infection increased from 218 per 100,000 inhabitants in 2003 to 263 per 100,000 in 2007. Although mortality rates decreased markedly (from 24 per 1000 HIV-infected patients in 2003 to 16 per 1000 in 2007), the data show that mortality was still higher in HIV-infected patients compared with the general population in the most recent years (SMR 8.8 in 2007). In each year included in the study, HIV-infected patients had higher rates of care-seeking for chronic diseases, including liver diseases (SHR>8), neuropathy, oesophagus-gastro-duodenum diseases, serious psychiatric disorders and renal failure (SHR approximately 3 for each). Also, the rate of medical attendance for neoplasias, chronic pulmonary disease, diabetes, and cardiovascular disease increased over time in HIV-infected patients compared with the general population. Ranking diseases in order of their total cost to the health system, HIV infection ranked 12th, with total costs of €28.6 million in 2007. Ranking in order of cost per patient, HIV infection ranked third, with a cost per patient of €9894 in 2007. HIV-infected patients with concomitant chronic diseases had higher average costs. The cost per patient in 2007 was €8104 for HIV-infected patients without other chronic diseases, €9908 for HIV infection plus cardiovascular disease, €11,370 for HIV infection plus chronic liver disease and €12,013 for HIV infection plus neoplasias. CONCLUSIONS: The prevalence and population cost of people living with HIV are likely to increase as a result of prolonged survival, aging of HIV-infected patients and increased risk of other chronic diseases. In the near future, HIV infection will rank as one of the most costly chronic diseases. Prevention strategies need to be more widely adopted to control the growing burden of the HIV epidemic and other chronic diseases affecting HIV-infected patients.

Levonorgestrel antagonism on estrogen-induced pituitary tumors is mediated by progesterone receptors.

Using both IN VITRO and IN VIVO approaches, we studied the antagonism exerted by the synthetic progestin levonorgestrel on estrogen-induced prolactinomas, considering that levonorgestrel shows partial androgenic properties and that androgens inhibit estrogen-induced prolactin synthesis and secretion. In the tumors, binding of estrogens to their receptors was competed neither by progesterone receptor ligands nor by androgen receptor ligands, ruling out direct inhibitory effects of these drugs on tumor development. Progestin binding was competed by the progesterone receptor agonists progesterone and levonorgestrel, by the antagonist mifepristone, and also by the androgen dihydrotestosterone, whereas the androgen receptor antagonist hydroxyflutamide was a weak competitor. In addition, both progesterone receptor and androgen receptor ligands competed for binding to androgen receptors. In primary cultures of pituitary tumors, levonorgestrel decreased prolactin secretion, an effect that was blocked by mifepristone but not by hydroxyflutamide. IN VIVO results indicated that levonorgestrel inhibition of both estrogen-induced pituitary weight increment and hyperprolactinemia was reduced by mifepristone, whereas flutamide was unable to block levonorgestrel effects. Our results suggest that even when an interaction of levonorgestrel with androgen receptors in the tumors is possible, the antagonistic effects of levonorgestrel on tumor development and functionality are mediated by progesterone receptors.

In vitro oocyte maturation, fertilization and culture after ovum pick-up in an endangered gazelle (Gazella dama mhorr).

The recovery of immature oocytes followed by in vitro maturation, fertilization and culture (IVMFC) allows the rescue of biological material of great genetic value for the establishment of genetic resource banks of endangered species. Studies exist on sperm cryopreservation of endangered Mohor gazelle (Gazella dama mhorr), but no work has been carried out yet on oocyte collection, fertilization and culture in this or related species. The purpose of this study was to develop a protocol for ovarian stimulation for the recovery of oocytes and subsequent IVMFC in the Mohor gazelle using frozen-thawed spermatozoa. Ovum pick-up was performed after ovarian stimulation with a total dose of 5.28 mg of ovine FSH. A total of 35 oocytes were recovered from 56 punctured follicles (62%) (N=6 females). Out of 29 cumulus-oocyte complexes matured in vitro, 3% were found at germinal vesicle stage, 7% at metaphase I, 21% were degenerated, and 69% advanced to metaphase II. Fertilization and cleavage rates of matured oocytes were 40 and 30%, respectively. Embryos cleaved in vitro up to the 6-8 cell stage but none progressed to the blastocyst stage, suggesting the existence of a developmental block and the need to improve culture conditions. Although more studies are needed to improve hormonal stimulation and oocyte harvesting, as well as IVMFC conditions, this study demonstrates for the first time the feasibility of in vitro fertilization with frozen-thawed semen of in vitro matured oocytes collected by ovum pick-up from FSH-stimulated endangered gazelles.

First Italian consensus statement on diagnosis, prevention and treatment of cardiovascular complications in HIV-infected patients in the HAART era (2006).

The present document contains recommendations for assessment, prevention and treatment of cardiovascular risk for HIV-infected patients. All recommendations were graded according to the strength and quality of the evidence and were voted on by 73 members of the Italian Cardiovascular Risk Guidelines Working Group which includes both experts in HIV/AIDS care and in cardiovascular and metabolic medicine. Since antiretroviral drug exposure represents only one risk factor, continued emphasis on an integrated management is given. This should include prevention and treatment of known cardiovascular risk factors (such as dyslipidaemia, diabetes, insulin resistance, healthy diet, physical activity, avoidance of smoking), but also rational switch of antiretroviral drugs. A rational switch strategy should consider both metabolic and anthropometric disturbances and effectiveness of antiretroviral regimens.

Effect of pentoxifylline on levels of pro-inflammatory cytokines during chronic hepatitis C.

The cellular and humoral natural immune response induced by hepatitis C virus (HCV) is commonly unable to eradicate the virus. HCV is a highly mutable, hepatotropic RNA virus that causes acute and chronic hepatitis, an infection that involves the production of various cytokines. The aim of the study is to analyse the expression of pro-inflammatory cytokines IL-1beta, TNF-alpha, IFN-gamma and the chemokine CXCL8 (IL-8) in liver tissue and their expression and secretion in PBMC of patients with chronic hepatitis C (CHC), in response to pentoxyfilline (PTX). We studied six CHC patients, naive to treatment. Patients received PTX 400 mg twice a day/8 weeks. Pentoxyfilline resulted in decreased expression of mRNA of liver IL-1beta, TNF-alpha and IFN-gamma: 144.2 versus 83.5 molecules of IL-1beta (P < 0.05), TNF-alpha 194.3 versus 17.6 molecules (P = 0.03) and IFN-gamma 26.1 versus 0.5 molecules (P = 0.04). Following PTX, PBMC exhibited a decrease in IFN-gamma mRNA 12.2 versus 1.5 molecules (P = 0.028) and CXCL8 4.2 versus 2.5 molecules (P = 0.027). In PBMC, only the secretion of TNF-alpha was decreased 1109 versus 933.5 pg/ml, P = 0.046. Production of cytokines both locally (within the liver) and systemically (PBMC) may serve as biomarkers of the infection with hepatitis C. PTX inhibits the expression of several pro-inflammatory cytokines in the liver. These results indicate that it is worth exploring PTX in hepatitis in future clinical trials in nonresponders to antiviral treatment.

Progesterone primes zona pellucida-induced activation of phospholipase A2 during acrosomal exocytosis in guinea pig spermatozoa.

We investigated, using guinea-pig spermatozoa as a model, whether phospholipase A2 (PLA2) is involved in progesterone or zona pellucida (ZP)-stimulated acrosomal exocytosis, if progesterone enhances ZP-induced activation of PLA2, and mechanisms underlying PLA2 regulation. Spermatozoa were capacitated and labeled in low Ca2+ medium with [14C]choline chloride or [14C]arachidonic acid, washed, and then exposed to millimolar Ca2+ and progesterone and/or ZP. Each agonist stimulated decrease of phosphatidylcholine (PC) and release of arachidonic acid and lysoPC, indicative of PLA2 activation. Aristolochic acid (a PLA2 inhibitor) abrogated lipid changes and exocytosis, indicating that these lipid changes are essential for exocytosis. Exposure of spermatozoa to submaximal concentrations of both progesterone and ZP resulted in a synergistic increase of arachidonic acid and lysoPC releases, and exocytosis, suggesting that, under natural conditions, both agonists interact to bring about acrosomal exocytosis. Progesterone-induced PLA2 activation appears to be mediated by a GABA(A)-like receptor, because bicuculline (a GABA(A) receptor antagonist) blocked arachidonic acid release and exocytosis. In agreement with this, GABA mimicked progesterone actions. ZP-induced activation of PLA2 seemed to be transduced via G(i) proteins because pertussis toxin blocked arachidonic acid release and acrosomal exocytosis. PLA2 may be regulated by PKC because progesterone- or ZP-induced release of arachidonic acid was blocked by the PKC inhibitors staurosporine or chelerythrine chloride. PLA2 could also be regulated by the cAMP-PKA pathway; inclusion of the PKA inhibitor 14-22 amide or H-89 led to a reduction in arachidonic acid release or exocytosis after progesterone or ZP. Taken together, these results suggest that PLA2 plays an essential role in progesterone or ZP-stimulated exocytosis with progesterone priming ZP action.

Risk factors for myocardial infarction in HIV-positive patients.

We describe the clinical characteristics of 12 HIV-infected patients who suffered from myocardial infarction (MI) in our clinical cohort. They were compared with a control group matched (1:2) for factors related to cardiovascular risk (age, gender, smoking habit, risk factor for HIV acquisition, hypertension, family history for relevant cardiovascular events, and body mass index) by conditional (fixed-effect) logistic regression analysis. Among patients with MI, 6/12 had never used protease inhibitors (PIs) or were antiretroviral therapy naive. The only variables marginally associated with MI were nadir CD4+ T-cell count <50/mm(3) (odds ratio (OR): 7.2; 95% confidence interval (CI) 0.81-64.2; P: 0.077) and zenith >100,000 HIV RNA copies/mL (OR: 7; 95% CI 0.81-60.2; P: 0.076) at univariate analysis. Moreover, the use of PIs did not result in being associated with the risk of MI. Our data show that in HIV-infected patients, PI use does not seem to have any negative impact on MI while the possible impact of advanced HIV infection itself needs further investigations.

HIV/HTLV co-infection: frequency and epidemiological characteristics among patients admitted to an Italian hospital.

BACKGROUND: Human T-cell leukemia/lymphoma viruses (HTLV) and HIV share identical modes of transmission and co-infections may be detected in populations that are highly exposed to common risk factors. MATERIALS AND METHODS: A total of 599 serum samples from HIV-positive patients attending our outpatient clinic during the last semester of 2000 were tested to assess the prevalence of HTLV co-infection in both Italian (n = 472) and non-European HIV-infected patients (n = 127). RESULTS: 72 samples were positive for HTLV-II. Most of the HTLV-II-positive patients were Italian (71/72, 98.6%) and 98.5% of them had acquired the HIV infection through use of intravenous recreational drugs. CONCLUSION: These data demonstrate a high HTLV-II exposure among HIV-positive intravenous drug users in our area which was not previously considered to be an area of endemicity for HTLV-II.

Modulation of cytosolic calcium levels in osteoblast-like osteosarcoma cells by olpadronate and its amino-derivative IG-9402.

The molecular mechanisms as well as the structure/activity relationships involved in the antiresorptive actions of bisphosphonates on bone cells are still not clear. Replacement of the R1-hydroxyl by an NH2 group in olpadronate (OPD) abolishes its antiresorptive activity. We show here that in the rat osteosarcoma-derived osteoblast-like ROS 17/2.8 cell line, OPD and IG-9402 (NH2-OPD; [3-(N,N-dimethylamine)-1-aminopropylidene bisphosphonate]), similar to 1,25(OH)2-vitamin D3, rapidly modulate cytosolic calcium levels ([Ca2+]i). As for the steroid hormone, the osteosarcoma cell Ca2+i response to OPD was rapid (30 sec) and sustained (>5 min), exhibiting a biphasic profile. The response to IG-9402 was also fast but smaller than that of OPD and 1,25(OH)2D3, and rapidly declined to levels near basal. The effect of these bisphosphonates on [Ca2+]i was dose-dependent, being maximal at 10(-8) M and was not observed in non-bone cellular systems, e.g., skeletal muscle and breast cells. Pretreatment of the ROS 17/2.8 cells with the Ca2+ channel blockers nifedipine and verapamil markedly reduced (>70%) the influx phase of the response to OPD and almost completely inhibited that of IG-9402, indicating the participation of voltage-dependent Ca2+ channels in the action of both compounds. Moreover, preincubation with the phospholipase C inhibitors U73122 and neomycin or depletion of inner stores with thapsigargin completely blocked the response to either olpadronate or its amino-derivative. Both OPD and IG-9402 significantly increased osteocalcin release into the culture medium of osteosarcoma cells. The results support the involvement of the Ca2+ signaling pathway as part of the mechanism by which bisphosphonates induce bone cellular responses.

The effect of dithiothreitol on VLA-4 detection in peripheral blood and induced sputum cells.

BACKGROUND: Induced sputum has been shown to be a reliable technique for investigating airway inflammation non-invasively. Flow cytometry could provide useful information in this area. However, the viscosity of the sample entails the use of a mucolytic agent. Dithiothreitol (DDT) is the most frequently used agent although it could affect detection of different inflammatory markers. METHODS: To measure the effect of DDT on the detection of certain adhesion molecules in eosinophils and lymphocytes, sputum was induced from seven non-smoking asthmatic and non-asthmatic subjects treated with 0.1 M DDT. The samples were analyzed by flow cytometry. Whole blood samples from the same subjects were also processed with DTT and analyzed by flow cytometry. RESULTS: Very late activated antigen-4 (VLA-4) levels on eosinophils in intracellular and surface staining were much lower than expected. VLA-4 on lymphocytes was also altered but less so than on eosinophils. VLA-4 levels were also decreased on blood cells after DTT treatment. No abnormalities were found in the detection of CD29 on eosinophils and the beta7-chain in lymphocytes. CONCLUSIONS: Flow cytometry could be used as a complementary method to induced sputum in the investigation of airway inflammation. However, DTT could interfere with the detection of some inflammatory markers, as is the case with VLA-4.

SHP-1 expression in peripheral T cells from patients with Sezary syndrome and in the T cell line HUT-78: implications in JAK3-mediated signaling.

SHP-1 is a key tyrosine phosphatase that acts as a negative regulator of signal transduction in lymphocytes, which has been found down-regulated in several T cell lines derived from human T cell malignancies. The standardization of a sensitive ELISA for the quantification of SHP-1 protein in peripheral T and B lymphocytes has enabled us to quantify the SHP-1 content of freshly isolated T cells from patients with Sezary syndrome and in the Sezary T cell line HUT-78. In all cases, a dramatic decrease in the content of this protein, when compared with the content in healthy volunteer controls, was observed. These results were corroborated when the expression of SHP-1 mRNA was analyzed. In order to study whether there was any correlation between SHP-1 protein expression and tyrosine phosphorylated state of JAK3, the state of phosphorylation of JAK3 was studied in the T cell line HUT-78, and found to be highly phosphorylated. These results suggest that SHP-1 might be involved in maintaining the IL-2R/JAK3 signaling pathway under control and point towards a role of SHP-1 in the pathogenesis of the disease.