Aims: Cytoplasmic accumulation of the nuclear protein transactive response DNA-binding protein 43 (TDP-43) is an early determinant of motor neuron degeneration in most amyotrophic lateral sclerosis (ALS) cases. We previously disclosed this accumulation in circulating lymphomonocytes (CLM) of ALS patients with mutant TARDBP, the TDP-43-coding gene, as well as of a healthy individual carrying the parental TARDBP mutation. Here, we investigate TDP-43 subcellular localization in CLM and in the constituent cells, lymphocytes and monocytes, of patients with various ALS-linked mutant genes. Methods: TDP-43 subcellular localization was analysed with western immunoblotting and immunocytofluorescence in CLM of healthy controls (n = 10), patients with mutant TARDBP (n = 4, 1 homozygous), valosin-containing protein (VCP; n = 2), fused in sarcoma/translocated in liposarcoma (FUS; n = 2), Cu/Zn superoxide dismutase 1 (SOD1; n = 6), chromosome 9 open reading frame 72 (C9ORF72; n = 4), without mutations (n = 5) and neurologically unaffected subjects with mutant TARDBP (n = 2). Results: TDP-43 cytoplasmic accumulation was found (P < 0.05 vs. controls) in CLM of patients with mutant TARDBP or VCP, but not FUS, in line with TDP-43 subcellular localization described for motor neurons of corresponding groups. Accumulation also characterized CLM of the healthy individuals with mutant TARDBP and of some patients with mutant SOD1 or C9ORF72. In 5 patients, belonging to categories described to carry TDP-43 mislocalization in motor neurons (3 C9ORF72, 1 TARDBP and 1 without mutations), TDP-43 cytoplasmic accumulation was not detected in CLM or in lymphocytes but was in monocytes. Conclusions: In ALS forms characterized by TDP-43 mislocalization in motor neurons, monocytes display this alteration, even when not manifest in CLM. Monocytes may be used to support diagnosis, as well as to identify subjects at risk, of ALS and to develop/monitor targeted treatments.

Invasive fungal infections in preterm neonates in the neonatal intensive care unit are predominantly caused by Candida spp, and have a high burden of morbidity and mortality. Effective prophylactic strategies have recently become available, but the identification of the best possible strategies to manage high-risk infants is still a priority. Choice and use of appropriate antifungal drugs needs careful assessment of neonatal characteristics, the epidemiology and drug pharmacokinetics. Ideally, antifungal drugs for preterm neonates should target fungal bio-films, prevent or effectively treat end-organ localisations, be active against fluconazole-resistant Candida species, and have reliable safety and tolerability profiles. The paper reviews the state-of-the-art in the area of neonatal fungal infections, and addresses some open questions related to the best possible prophylactic and therapeutic strategies to be implemented in such unique patients.

Bronchopulmonary dysplasia (BPD) continues to represent a significant cause of morbidity among survivors of severe prematurity in the NICU. The increasing prevalence of BPD over the decades has been suggested to be related to the increased survival of extremely low birthweight infants.To evaluate differences in prevalence of BPD (BPD28d and BPD36wk) and as a function of survival rate in extremely low birth weight (ELBW) infants over time, and to explore its relationship with known associated risk factors.Survival rate and prevalence of oxygen-dependency =28 days (BPD28d) and oxygen-dependency =36 weeks postmenstrual age (BPD36wk) were evaluated in ELBW newborns (mean gestational age: 27.12.2 weeks; mean birth weight: 817142 g) consecutively admitted to the Brindisi NICU over the last 26 years. Two arbitrarily chosen time periods were compared: Period 1: July 1st, 1986 to June 30, 2002 vs. Period 2: July 1st, 2002 to December 31, 2012. Analyzed variables included gestational age, birth weight, intubation time, hours of O2 administration, NCPAP, and use of surfactant. Differences between the time periods were assessed by chi-square statistics, Fisher's tests or Mann–Whitney test, as appropriate. A two-tailed p value <0.05 was considered to indicate statistical significance.Survival rate of ELBW infants over the examined time periods dramatically improved from 42.3% to 72.6% (p < 0.0001), whereas changes in the prevalence of BPD28d and BPD36wk were not statistically significant (30.5% vs. 39.3%, p = 0.2137 and 5.5% vs. 13.1%, p = 0.1452, respectively). Likewise, BPD severity was not significantly different between the two time periods (p = 0.1635). Gestational age and birth weight of surviving neonates did not significantly change between the two time periods (p = 0.8050 and p = 0.6986, respectively), whereas significantly increased intubation time (median values: 144 hours vs. 33 hours, p <0.0001) and use of exogenous surfactant (89.3% vs. 48.6%, p < 0.0001) was evidenced for the second time period, as well as NCPAP (median values: 600 hours vs. 377 hours, p = 0.0005). A statistically non-significant trend for a prolonged O2 administration in period 2 (p = 0.0850) was also observed.Our findings indicate that a significantly increased survival is not necessarily associated with a significant difference in the prevalence of BPD among ELBW infants.

Background: Fungal colonisation by Candida spp. affects a high proportion of VLBW neonates in NICU. However, few data are available on the clinical characteristics of colonisation in preterm infants who are colonised at baseline via vertical transmission, compared to preterms who become colonised during their stay in NICU via horizontal transmission.Material and Methods: We reviewed the database of a multicentre, randomised trial of prophylactic fluconazole in VLBW neonates conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM 2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly surveillance cultures from birth till discharge. We investigated the frequency of the two different modalities of Candida colonisation in this population, as well as the clinical and outcome characteristics possibly related to them.Results: Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e., detected <3rd day of life) colonisation affected 16 (4.7%), and acquired 38 (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had significantly higher birth weight (1229 28g vs. 1047g +/- 29, p=0.01) and gestational age (30.2 wks 2.7 vs. 28.5 wks 2.6, p=0.01), and were significantly more likely to limit progression from colonisation to invasive Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p=0.009). Isolation of C. parapsilosis was significantly more frequent in infants with acquired colonisation.Conclusions: Infants with baseline and acquired colonisation differ for demographics characteristics and for their response to fluconazole prophylaxis. This information may be useful for targeting more accurate management strategies for these two different groups of colonised preterms in NICU. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Invasive disseminated neonatal aspergillosis is an uncommon disease, with only scattered reports in literature in the last few years. Here we report on a 25-week gestational age, 730 g at birth preterm female infant who developed on day-of-life 10 multiple cutaneous exhulcerative lesions in her right arm, trunk and abdomen. Early recognition and diagnosis of these lesions as a due to cutaneous initial symptom of cutaneous disseminated aspergillosis, as well as prompt treatment with Liposomal amphotericin B + Itraconazole, secured successful recovery from the systemic infection. Skin lesions healed without any surgical treatment. The infant was discharged in good health. Long-term follow-up at three years of age revealed normality of all neurodevelopmental and cognitive parameters. To our knowledge, this is one of the very few cases of survival, free from sequelae, for a preterm infant affected by neonatal cutaneous disseminated aspergillosis.

Neonatal congenital infections are an important cause of mortality, morbidity and long-term neurodevelopmental and sensorineural sequelae. Many pathogens can cause in utero infection, and among them, cytomegalovirus (CMV) plays a prominent role. In developed countries, CMV poses major health problems as it is the most common pathogen leading to congenital infection, and the leading cause of nonhereditary deafness in children. Evaluation of central nervous system (CNS) involvement in congenital CMV infected newborns is mandatory to better assess the severity of the disease, to guide adequate treatment, to define prognosis, and to tailor follow-up observations and parents' counselling. Cerebral ultrasonography (cUS), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) are the currently available techniques to evaluate infants with suspected or proven congenital CMV infection. In congenital CMV infection, their role in early detection and confirmation of cerebral involvement within the first month of life is crucial to initiate specific treatment with antivirals. Neonatologists, paediatricians and radiologists should be aware of the role, the limitations and the inherent risks related to the use of these specific neuroimaging diagnostic tools in these infants. In this article we will discuss from a neonatological perspective the advantages, disadvantages, risks and limitations of each imaging technique.

Neonatal sepsis cause severe morbidity and mortality. Neonates in NICU feature many specific risk factors for bacterial and fungal sepsis. Loss of gut commensals such as Bifidobacteria/Lactobacilli, as occurs with prolonged antibiotic treatments, delayed enteral feeding, or nursing in incubators, translates into proliferation of pathogenic microflora and abnormal gut colonization, Prompt diagnosis and effective treatment do not protect septic neonates from the risk of late neurodevelopmental impairment in the survivors, thus specific prevention is mandatory in these particular settings. In this view, improving Neonatal Management is a key step. This include promoting Breastfeeding and Hygiene measures, cautious CVC management, enhancing Enteric microbiota composition with Probiotics, and medical stewardship concerning H2-blockers/steroids restrictions. A new approach towards reduction of sepsis and NEC might involve the use of bioactive substances with known anti-infective properties. Lactoferrin is a mammalian milk glycoprotein involved in innate immune host defences, and can reduce the incidence of late-onset sepsis in VLBW infants (MANZONI JAMA 2009) and of NEC in animal models. The bovine isoform is nearly homologous to the human one. Lactoferrin targets all pathogens, has bifidogenic properties, and enhance maturation of the nascent gut. In a recent RCT, bovine LF produced a 65% decrease in any-cause LOS, and significant decrease in both surgical and low-stages NEC (MANZONI PAS 2011). As no adverse effects or intolerances to treatment have been reported to date, the role of LF in the management of infections and NEC in NICU looks very promising and worthy of future, larger-sized trials to confirm these findings.

Duodenal obstruction is one of the most common congenital anomalies. Both intrinsic (atresia, web and stenosis) or extrinsic lesions (malrotation, peritoneal bands, intestinal duplication, anterior portal vein and annular pancreas) may be involved. It usually presents within the first week of life with vomiting. We report an unusual congenital duodenal obstruction in a 8-month-old female with atypical symptoms due to a combination of intrinsic and extrinsic lesions.

Late-onset sepsis (LOS) affects a large proportion of pre-term neonates in neonatal intensive care units (NICUs) worldwide, with high morbidity and related mortality, and frequent occurrence of severe late neurodevelopmental impairment. Due to the frequency, severity and difficulties in early diagnosis and prompt therapy, prevention is crucial for decreasing the burden of infection-related complications in NICUs.

Un episodio di sepsi si verifica nel 20-40% dei pazienti pretermine e queste cifre sono in costante aumento nelle Unità di Terapia Intensiva Neonatale (TIN). Le sepsi neonatali comprendono infezioni a partenza da sangue, urine, liquido cerebro-spinale e peritoneale, infezioni da ustioni e ferite o da altri siti di solito sterili. Molti fattori specifici giustificano l’aumento del rischio, tra cui l’uso di antibiotici ad ampio spettro che selezionano una microflora resistente, la nutrizione parenterale, gli inibitori dell’acidità gastrica e gli steroidi, così come l’uso sistematico e duraturo di procedure invasive. Nei neonati pretermine, la perdita dei commensali intestinali, come lattobacilli e bifidobatteri a causa delle difficoltà di nutrizione per via orale, o una più lenta loro acquisizione, si traduce in un aumento di suscettibilità alla colonizzazione dell’intestino da parte di patogeni. Una diagnosi tempestiva, un trattamento efficace e la profilassi specifica con farmaci antibatterici e antimicotici sono le pietre miliari della gestione di questi eventi potenzialmente mortali in ogni TIN. Vengono illustrati i recenti progressi nella prevenzione e si dimostra come il fluconazolo per la prevenzione della sepsi fungina, i probiotici per la prevenzione della entercolite necrotizzante e la lattoferrina bovina per la prevenzione della sepsi batterica possono essere considerati come efficaci strategie.

Preterm neonates in neonatal intensive care units (NICU) are at high risk of invasive fungal infection (IFI), mostly by Candida spp. IFI in such patients is increasingly leading to high morbidity and mortality and frequent neurodevelopmental disabilities in the survivors. Most conditions and risk factors associated with neonatal IFI are unavoidable, being intrinsic to prematurity or related to the aggressive nature of the care these patients require. Neonatal IFI is difficult to diagnose, as candidaemia may be transient and difficult to eradicate due to the high rates of end-organ dissemination. The best option to decrease the burden of disease is thus to prevent it. Fluconazole administration is a suitable strategy and proved effective in many retrospective, single-centre studies and in four randomised, prospective clinical trials. Nevertheless, the use of this azole in high-risk preterm neonates in NICU is not yet a standard of care. This article summarises current evidence on the use of fluconazole in preterm neonates and discusses the concerns surrounding its use in nurseries.

In circulating lymphomonocytes (CLM) of patients with Type 2 diabetes (DM2) pyruvate dehydrogenase (PDH), the major determinant of glucose oxidative breakdown, is affected by a cohort of alterations reflecting impaired insulin-stimulated glucose utilization. The cohort is also expressed, although incompletely, in 40% of healthy young subjects with a DM2-family history (FH). Pregnancy restrains glucose utilization in maternal peripheral tissues to satisfy fetal requirements. Here we explore whether pregnant women develop the PDH alterations and, if so, whether there are differences between women with and without FH (FH+, FH−). Ten FH+ and 10 FH — were evaluated during pregnancy (12–14, 24–26, and 37–39 weeks) and 1 yr after (follow-up) for fasting plasma glucose and insulin as well as body mass index (BMI), and for the PDH alterations. Twenty FH — and 20 FH+ non-pregnant women served as controls. All FH+ and FH — controls exhibited normal clinical parameters and 8 FH+ had an incomplete cohort of PDH alterations. In FH — and FH+ pregnant women at 12–14 weeks clinical parameters were normal; from 24–26 weeks, with unvaried glucose, insulin and BMI rose more in FH — and only in the latter recovered the 12–14 weeks values at follow-up. In all FH−, the cohort of PDH alterations was incomplete at 24–26 weeks, complete at 37–39 weeks, and absent at follow-up but complete from 12–14 weeks including follow-up in all FH+. In FH−, the cohort is an acquired trait restricted to pregnancy signaling transiently reduced insulin-stimulated glucose utilization; in FH+, instead, it unveils the existence of an inherited DM2-related background these women all have, that is awakened by pregnancy and as such lastingly impairs insulin-stimulated glucose utilization.

Aim: The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. Methods: We performed a case-control study on neonates with birthweight less than 1250 g admitted to our tertiary-level unit during the years 1998- 2004 (n = 383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late-onset sepsis caused by bacterial agents (n = 46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia > 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. Results : Hyperglycaemia occurred significantly more often in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235-4.432, p = 0.008). Moreover, in 19 of 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p = 0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15).Conclusions: Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late-onset sepsis, with a typical 3-d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur.

Background. Colonization by Candida species is the most important predictor of the development of invasive fungal disease in preterm neonates, and the enteric reservoir is a major site of colonization. We evaluated the effectiveness of an orally supplemented probiotic (Lactobacillus casei subspecies rhamnosus; Dicoflor [Dicofarm spa]; 6 x 10(9) cfu/day) in the prevention of gastrointestinal colonization by Candida species in preterm, very low birth weight (i.e., < 1500-g) neonates during their stay in a neonatal intensive care unit.Methods. Over a 12-month period, a prospective, randomized, blind, clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit. During the first 3 days of life, the neonates were randomly assigned to receive either an oral probiotic added to human (maternal or pooled donors') milk (group A) or human milk alone (group B) for 6 weeks or until discharge from the NICU, if the neonate was discharged before 6 weeks. On a weekly basis, specimens obtained from various sites (i.e., oropharyngeal, stool, gastric aspirate, and rectal specimens) were collected from all patients for surveillance culture, to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract.Results. The incidence of fungal enteric colonization (with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site) was significantly lower in group A than in group B (23.1% vs. 48.8%; relative risk, 0.315 [95% confidence interval, 0.120-0.826]; P=0.1). The numbers of fungal isolates obtained from each neonate (P=.005) and from each colonized patient (P=.005) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001-1500 g. There were no changes in the relative proportions of the different Candida strains. No adverse effects potentially associated with the probiotic were recorded.Conclusions. Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by Candida species among very low birth weight neonates.

OBJECTIVE:To determine whether an association exists between either fungal or bacterial sepsis and retinopathy of prematurity (ROP).STUDY DESIGN:Retrospective cohort study on all neonates with birth weight <1500 g admitted to a large Italian third Level Neonatal Intensive Care Unit in the years 1997-2001 and screened for ROP. Univariate analysis and multiple logistic regression were used to detect significant associations with ROP (all grades and threshold) in neonates with birth weight<1000 g (extremely low birth weight (ELBW)) and 1000-1500 g.RESULTS:Among 301 enrolled neonates, ROP (all grades), threshold ROP, fungal and bacterial sepsis occurred in 31.9, 12.9, 11.6 and 40.5% of the infants, respectively. At multivariate analysis, only gestational age (P=0.03), colonization by Candida non-albicans spp (P=0.03) and fungal sepsis (P=0.03) were independent predictors of threshold ROP, and only in ELBW neonates.CONCLUSIONS:Fungal (but not bacterial) sepsis is significantly and independently associated with ROP, but only in ELBW neonates and only with threshold ROP.

OBJECTIVE:Despite the promising preliminary results observed in extremely low birth weight (ELBW) populations, the use of fluconazole to prevent fungal colonization and infection in preterm neonates in the NICU is still an open question and not yet recommended as a standard of care. We have reviewed our 6-year series to assess the effectiveness and safety of this form of prophylaxis. METHODS:This retrospective study consisted of 465 neonates who weighed < 1500 g at birth and were admitted to our NICU in the period 1998-2003. Those who were born between 1998 and 2000 and did not receive fluconazole prophylaxis (group A, n = 240) were compared with those who were born between 2001 and 2003 and treated with fluconazole until the 30th day of life (45th for neonates < 1000 g at birth; group B, n = 225). Weekly surveillance cultures were obtained from all patients. Incidence of fungal colonization, incidence of systemic fungal infection (SFI), rate of progression from colonization to infection, and mortality rates attributable to fungi were calculated for both groups and separately for neonates who were < 1000 g (ELBW) and were 1001 to 1500 g (NE-VLBW) at birth. RESULTS:Overall fungal colonization was significantly lower in group B (24.0%) than in group A (43.8%; relative risk [RR]: 0.406; 95% confidence interval [CI]: 0.273-0.605). The same was true of neonates with colonization in multiple sites (2.6% vs 5.8%) and of those with colonization from high-risk sites (5.8% vs 19.2%). SFI incidence was significantly lower in group B (10 of 225 cases; 4.4%) than in group A (40 of 240 cases; 16.7%; RR: 0.233; 95% CI: 0.113-0.447). Reduction of both colonization and SFI in group B was greater in the ELBW neonates and also significant in the NE-VLBW neonates. Rate of progression from colonization to infection was significantly lower in group B (0.17 vs 0.38; RR: 0.369; 95% CI: 0.159-0.815). Crude mortality rate attributable to Candida species was 1.7% (4 of 240) in group A vs 0% (0 of 225) in group B. Overall mortality rate (any cause before hospital discharge) was similar in the two groups (11.2% vs 10.6%), but in colonized infants (n = 159), it was significantly lower in group B (3.7% vs 18.1%; RR: 0.174; 95% CI: 0.039-0.778). The incidence of natively fluconazole-resistant fungal species did not increase over the years, and patterns of sensitivity to fluconazole remained the same. No adverse reaction related to fluconazole occurred. CONCLUSIONS:Prophylactic fluconazole significantly reduces the incidence of colonization and systemic infection by Candida species in both ELBW and NE-VLBW neonates and decreases the rates of progression from initial colonization to massive colonization and to systemic infection. All VLBW neonates may benefit from fluconazole prophylaxis.

Objective: The objective of this study was to determine whether down-regulation of pyruvate dehydrogenase phosphatase (PDP) is responsible for poorly active pyruvate dehydrogenase (PDH) in circulating lymphocytes (CLs) of obese subjects (ObS), and if so, whether it improves when their plasma insulin rises.Research Methods and Procedures: PDH activity was compared in lysed CLs of 10 euglycemic ObS and 10 sex-and age-matched controls before and during plasma insulin enhancement in an oral glucose tolerance test. It was evaluated without (PDHa) or with Mg/Ca or Mg at various concentrations to assess PDP1 or PDP2 activities or with Mg/Ca and exogenous PDP to determine total PDH activity (PDHt), which is an indirect measure of the amount of PDH. The insulin sensitivity index was calculated, and PDP1 and PDP2 mRNA was sought in the CLs.Results: At To in ObS, PDHt was normal, whereas PDHa and PDP1 activity was below normal at all Mg/Ca concentrations. PDP2 activity was undetectable in both groups. PDP1 and PDP2 mRNA was identified, and insulin sensitivity index and PDHa were directly correlated. During the oral glucose tolerance test, plasma insulin rose considerably more in ObS than in controls; PDHa and PDP1 activity also increased but remained significantly below normal, and PDHt was unvaried in both groups.Discussion: PDPI is down-regulated in CLs of ObS because it is poorly sensitive to Mg/Ca; this defect is attenuated when plasma insulin is greatly enhanced.

BACKGROUND:In HIV-infected patients some clinical and immunological benefits of antiretroviral therapy, which frequently include a combination of HIV protease inhibitors (PIs) and reverse transcriptase inhibitors (RTIs), cannot be solely explained by the drugs' action on viral enzymes. Proteasomes constitute the central protease of the ubiquitin ATP-dependent pathway involved in many cellular processes, as well as in HIV maturation and aggressiveness.OBJECTIVE:To explore whether the PIs nelfinavir and saquinavir and the RTIs abacavir, nevirapine, delavirdine, stavudine and didanosine affect proteasome function in vitro and in vivo.METHODS:Peptidase activity of purified human 26S and 20S proteasomes was assayed with and without the drugs at different concentrations. Intracellular proteasome proteolytic activity was evaluated by searching for ubiquitin-tagged proteins in HL60 cells incubated with and without the drugs.RESULTS:At therapeutic dosages, nelfinavir and saquinavir inhibited proteasome peptidase activity and caused intracellular accumulation of polyubiquitinated proteins, a hallmark of proteasome proteolytic inhibition in vivo; the RTIs failed to evoke either effect.CONCLUSION:Proteasomes are targeted by the two PIs but not the RTIs. Therefore, in HIV-infected patients the beneficial effect of a therapy including one of the two PIs should partly rely on inhibition of host proteasome function.

In most tissues expressing MHC class I molecules, proteasomes incorporating IFN-γ-inducible subunits, defined immuno-proteasomes, exist together with constitutive proteasomes. In physiological conditions, the central nervous system expresses neither MHC class I molecules nor TAP1 and TAP2 transporters but besides being constitutive, it is unknown whether immuno-proteasomes are also present in this tissue. We present evidence that in human brain, the two types of proteasome exist suggesting that under physiological conditions, the mechanisms regulating expression of IFN-γ-inducible subunits as well as of MHC class I molecules and TAP1 and TAP2 transporters in nervous tissue, are not entirely coordinated.