The transcriptional repressor HDAC7 promotes apoptosis and c-Myc downregulation in particular types of leukemia and lymphoma.

The generation of B cells is a complex process requiring several cellular transitions, including cell commitment and differentiation. Proper transcriptional control to establish the genetic programs characteristic of each cellular stage is essential for the correct development of B lymphocytes. Deregulation of these particular transcriptional programs may result in a block in B-cell maturation, contributing to the development of hematological malignancies such as leukemia and lymphoma. However, very little is currently known about the role of transcriptional repressors in normal and aberrant B lymphopoiesis. Here we report that histone deacetylase 7 (HDAC7) is underexpressed in pro-B acute lymphoblastic leukemia (pro-B-ALL) and Burkitt lymphoma. Ectopic expression of HDAC7 induces apoptosis, leads to the downregulation of c-Myc and inhibits the oncogenic potential of cells in vivo, in a xenograft model. Most significantly, we have observed low levels of HDAC7 expression in B-ALL patient samples, which is correlated with the increased levels of c-Myc. From a mechanistic angle, we show that ectopically expressed HDAC7 localizes to the nucleus and interacts with the transcription factor myocyte enhancer factor C (MEF2C) and the corepressors HDAC3 and SMRT. Accordingly, both the HDAC7-MEF2C interaction domain as well as its catalytic domain are involved in the reduced cell viability induced by HDAC7. We conclude that HDAC7 has a potent anti-oncogenic effect on specific B-cell malignancies, indicating that its deregulation may contribute to the pathogenesis of the disease.

Clinical manifestations of Behçet's disease in 137 Italian patients: results of a multicenter study.

OBJECTIVE: To determine the type and frequency of clinical features of Behçet's disease in a population of Italian patients. METHODS: We retrospectively studied 137 Italian patients (76 males and 61 females, age at onset 29.6 +/- 12.2 [mean +/- SD] years) seen consecutively in nine different referral centers. The duration of follow-up at study entry was 10.9 +/- 8.2 years. Virtually all patients fulfilled the classification criteria developed by the International Study Group for Behçet's disease. The clinical manifestations of the patients were recorded by the attending physicians using specifically designed forms. RESULTS: The most frequent manifestations at disease onset were oral (78.3%) and genital aphthae (29.2%) followed by inflammatory ocular involvement (20%) and arthritis (14.2%). The commonest (>50% of cases) manifestations observed throughout the disease course were oral aphthae (99.3%), genital aphthae (62.8%), various cutaneous lesions including erythema nodosum (81.8%), and inflammatory ocular disease (60.6%). Panuveitis and posterior uveitis/retinitis occurred more frequently in males compared with females (28.9% versus 11.5% and 57.9% versus 36.1%, respectively; p < 0.05). 61.6% of our patients were HLA-B51 positive. CONCLUSION: Behçet's disease in Italian patients is characterized by a variety of clinical manifestations in agreement with the medical literature. Panuveitis and posterior uveitis/retinitis occur more frequently in male patients.

Association of MICA alleles and HLA-B51 in Italian patients with Behçet's disease.

OBJECTIVE: To evaluate the distribution of the MHC class I chain related gene A transmembrane (MICA-TM) alleles in Italian patients with Behçet's disease (BD), and to investigate the relative contribution of MICA alleles and HLA-B51 in the susceptibility and specific clinical features of BD. METHODS: A total of 69 consecutive Italian patients who satisfied the International Study Group criteria for BD were followed at rheumatology, ophthalmology, and neurology units during a 3 year period (1997-99). We selected 130 healthy subjects from the same geographic areas as controls. All patients and controls were examined for MICA microsatellite polymorphisms using polymerase chain reaction. Serological HLA class B51 typing was performed by a standard microlymphocytotoxicity technique. RESULTS: A strong association with HLA-B51 was observed in patients with BD (OR 5.7, 95% CI 2.8-11.3). The MICA-TM allele A6, in linkage disequilibrium with HLA-B51, was only slightly increased in patients compared to controls (60.9% vs 50.8%; p = NS). No significant associations between HLA-B51 or MICA-TM alleles and clinical subgroups, particularly central nervous system or eye involvement, were found. CONCLUSION: HLA-B51 is the most important susceptibility gene in BD. Association with MICA-A6, when it exists, is secondary to the strong linkage disequilibrium with HLA-B51.

Intercellular adhesion molecule-1 gene polymorphisms in Behçet's Disease.

OBJECTIVE: Intercellular adhesion molecule 1 (ICAM-1) is strongly expressed in vascular endothelial cells and perivascular inflammatory infiltrates in immunopathologic studies of Behçet's disease (BD) lesions. ICAM-1 genes may contribute to the inflammatory events responsible for the vessel damage in BD. We examined potential associations of ICAM-1 gene polymorphisms with BD susceptibility. METHODS: Case patients were 74 consecutive Italian patients with BD who were followed at the Bologna, Ferrara, Milano, Potenza, Prato, Reggio Emilia, and Trento rheumatology, ophthalmology, and neurology units over a 3 year period (1997-99) who satisfied the International Study Group criteria for BD; 228 healthy Italian blood donors from the same geographic areas were selected as control groups. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: The frequency of R241 was significantly higher in BD patients than in controls (20.3% vs 5.7%; p = 0.001, pcorr = 0.002, OR 4.2, 95% CI 1.9-9.3). The distribution of E/K 469 genotype was similar in patients and controls. Comparing patients with different clinical features, we found only a trend to higher frequency of R241 in patients with articular manifestations (21.4% vs 12.5%; p = 0.08). CONCLUSION: Our findings show that G/R 241 polymorphism of ICAM-1 is associated with BD susceptibility.

Optic neuropathy in Behçet's disease. Report of two cases.

Orbital magnetic resonance imaging demonstrated increased signal of the optic nerve in short time inversion recovery (STIR) images of two young women with unilateral visual blurring. In both, recurrent oral and genital ulcerations and papulopustular lesions appeared within the next 14-15 months, respectively, allowing a diagnosis of Behçet's disease. Optic neuropathy may be an early manifestation of Behçt's disease and clinical follow-up is crucial for its diagnosis.

HBV and HCV infection among non-European Union immigrants in North-East Italy.

The status of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among non-European Union (non-EU) immigrants in North-East Italy was evaluated. Among the 1683 individuals tested the prevalence of HBsAg was 8.9% (150 subjects) and of HBV antibodies (anti-HBc with/without anti-HBs) was 38.9% (654 subjects). The distribution of HBV serological markers showed significant differences according to region of origin; the highest prevalence of infection (76.9%) and carriage (16.1%) was found in immigrants from sub-Saharan Africa. Among the 933 individuals screened for HCV infection, prevalence of antibody was much lower (0.9%) than that observed in the Italian general population (3.2-12.6%). The large number of HBV carriers among immigrants could increase the number of new adult infections due to life-style habits or professional risks in the host population. In contrast, the risk of HCV spread from non-EU immigrants is very low.

Identification of a North American mosquito species, Aedes atropalpus (Diptera: Culicidae), in Italy.

In late September 1996, during a routine survey for Aedes albopictus in Italy, a population of Aedes atropalpus s.s. was discovered in the Veneto Region (northern Italy). Larvae were collected in 2 tire storage areas belonging to tire recapping companies that imported loads of car and large equipment used tires from eastern Europe and North America. Aedes atropalpus is found only in North America and hence it is the origin of this species. Control measures were carried out in October, but by then any remaining Ae. atropalpus would have been diapausing in the egg stage. A follow-up survey will be conducted in the spring of 1997 to assess if Ae. atropalpus has been established in the area and the extent of the spread in Italy.

Immunity status to polioviruses among non-European union immigrants in Veneto Region (North-East Italy).

Widespread use of poliovirus vaccines has lead to a dramatic decline on the incidence of paralytic poliomyelitis in the Western Hemisphere. In Italy, the use of live attenuated vaccine (OPV) has lead to virtual eradication of poliomyelitis. However, wild poliovirus is still endemic in some less developed countries, and there is still a risk of importation of wild-virus poliomyelitis as result of immigration from these areas. Therefore, a serologic study of the immunologic status to poliovirus was carried out in 242 immigrants from less developed countries in the Veneto Region (North-East Italy). The overall prevalence of serum neutralizing antibodies was 98.3 percent for poliovirus type 1, 99.6 percent for type 2, and 95.9 percent for type 3. The modal titres were 1:128 (21.1 percent), 1:512 (26.4 percent), and 1:32 (22.3 percent) for poliovirus type 1, type 2, and type 3, respectively. No subject was simultaneously lacking neutralizing antibodies to all three polioviruses. The mean duration of stay in Italy before testing was 1.53 years (range 1 month to 7 years). These results show a good level of the immunity status, similar to those found in the Veneto general population. Although the risk of paralytic poliomyelitis in our population is very low, seronegative immigrants originating from areas of high endemicity could reintroduce wild poliovirus. It is therefore important to maintain a careful surveillance system on the importation of wild poliovirus and to plan vaccination programs for unprotected immigrants.

Unaltered dopaminergic modulation of aldosterone secretion in cirrhosis.

1. The responses of plasma aldosterone and plasma prolactin concentrations to metoclopramide (10 mg intravenously) were evaluated over 2 h in eight healthy controls and in 23 patients with cirrhosis (10 without and 13 with ascites). Plasma renin activity, glomerular filtration rate and renal sodium excretion were also determined. 2. Metoclopramide did not significantly influence plasma renin activity, whereas both plasma aldosterone and plasma prolactin rose significantly. The incremental areas under the curves did not differ among controls and cirrhotic patients without and with ascites. No significant correlations between plasma prolactin and aldosterone, either under basal conditions or after metoclopramide administration, were found in either controls or patients. 3. Glomerular filtration rate did not change after metoclopramide. Renal sodium excretion in controls and cirrhotic patients without ascites was also unaffected, whereas it decreased significantly in cirrhotic patients with ascites. In the latter, renal sodium excretion was inversely correlated with plasma aldosterone both under basal conditions and after metoclopramide administration. 4. The dopaminergic control of aldosterone secretion does not appear to be significantly altered in cirrhosis. Metoclopramide administration to cirrhotic patients with ascites leads to an increase in plasma aldosterone that may enhance renal sodium retention.

Brain RNA synthesis and the retention of learning through metamorphosis in Tenebrio obscurus (Insecta: Coleoptera).

1. Neurochemical events associated with the retention of learning through metamorphosis in the tenebrionid beetle, Tenebrio obscurus, were investigated. 2. Retention of learning of a complex maze task was demonstrated for this species. 3. Learning was accompanied by a significant increase in RNA synthesis within the corpora pedunculata of both larval and adult stages of this holometabolous insect. 4. The implications of these results to the development of the insect CNS during various life cycle stages and the conservation of neural organization within those brain regions associated with the consolidation and storage of experiential information are discussed.

[Epidemiologic study on the distribution of HLA antigens in rheumatoid arthritis]. / Studio epidemiologico sulla distribuzione degli antigeni HLA nell'artrite reumatoide.

Serologic HLA typing was carried out on 71 seropositive and 40 seronegative patients with rheumatoid arthritis and compared with values in 134 normal controls. A significant increase of HLA DR4 antigen, compared with control values, was found only in seropositive rheumatoid arthritis; HLA A1 and B35 antigens were significantly increased in seronegative rheumatoid arthritis patients (p less than 0.05), when compared with control values, but only HLA A1 antigen remained significantly higher when the p-correct test was performed.

Reference ranges and methodological aspects in the urinary measuring of lysozyme, malate-dehydrogenase, gamma-glutamyltransferase and alpha-glucosidase.

The urinary excretions of lysozyme (LYS), malate-dehydrogenase (MAD), gamma-glutamyltransferase (GGT) and alpha-glucosidase (AGL) were measured in a group of normal subjects in basic conditions, during forced diuresis, at different hours of the day and with urinary collection periods of different lengths. The results have been expressed in the principal ways used in clinical practice. The best way to express the excretions of GGT and AGL was with the fractional excretions. For LYS and MAD, the fractional clearances appeared to be theoretically valuable. They were not significantly influenced by sex or by the different urinary collections. Forced diuresis caused a significant scattering of enzymuria.

[Vascular flow-regulating devices in the human kidney]. / Dispositive vasali regolatori di flusso nel rene umano.

Small arterious and venous vessels of the juxtamedullary cortex of normal human kidney present wall formations regulating the blood flow. The arterious devices appear either as sphincterial rings at the origins of collateral branches of interlobular arteries, or as groups of myoepithelioid cells in the wall of small arteries immediately preceding the afferent arterioles. The venular devices consist of circular muscular thickenings repeated along the course of the vessel.

[The presence of arteriovenous anastomoses in the human kidney]. / Sulla presenza di anastomosi arterovenose nel rene umano.

The microscopic observation of serial sections obtained from normal human kidneys allowed to demonstrate the presence of arteriovenous anastomoses in the juxtamedullary cortex. In particular one section is shown which clearly presents an anastomotic channel along with its connections to both an afferent arteriole and a venule.

Transient nephrogenic diabetes insipidus during toxemia in pregnancy.

A pregnant woman is presented who developed transient nephrogenic diabetes insipidus. The patient had chronic hypertension with evidence of superimposed toxemia. The association of nephrogenic diabetes insipidus and pregnancy is reviewed. To our knowledge this is the first description of a patient who developed nephrogenic diabetes insipidus during pregnancy.

Metastatic cerebral choriocarcinoma without pelvic or pulmonary metastases.

A unique case of chorionic carcinoma of the right frontal lobe of the brain with extensive subarachnoid and intracerebral hemorrhage is presented. No pelvic or pulmonary findings by physical or X-ray examination were present. The craniotomy, irradiation and chemotherapy effected a cure. A nephrectomy was necessary during the postoperative period.