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Remote sensing technologies have the potential to support monitoring of floating plastic litter in aquatic environments. An experimental campaign was carried out in a large-scale hydrodynamic test facility to explore the detectability of floating plastics in ocean waves, comparing and contrasting different microwave and optical remote sensing technologies. The extensive experiments revealed that detection of plastics was feasible with microwave measurement techniques using X and Ku-bands with VV polarization at a plastic threshold concentration of 1 item/m 2 or 1-10 g/m 2 . The optical measurements further revealed that spectral and polarization properties in the visible and infrared spectrum had diagnostic information unique to the floating plastics. This assessment presents a crucial step towards enabling the detection of aquatic plastics using advanced remote sensing technologies. We demonstrate that remote sensing has the potential for global targeting of plastic litter hotspots, which is needed for supporting effective clean-up efforts and scientific evidence-based policy making., (© 2024. The Author(s).)

Background: Non-valvular atrial fibrillation (NVAF) is a cardiac rhythm disturbance that increases the risk of stroke and is highly prevalent in Europe and Italy, increasingly with advancing age. Oral anticoagulation is a key component of stroke prevention in patients with NVAF, yet withdrawal or interruption of anticoagulation may transiently increase the risk of embolic events. Treatment persistence to anticoagulation is an important metric but one that is not well studied in patients with NVAF in Italy. The RITMUS-AF study aims to evaluate the persistence with rivaroxaban treatment for stroke prevention in patients with NVAF in Italy., Methods: RITMUS-AF is a prospective, observational cohort study of patients with NVAF in hospital cardiology departments with a non-vitamin K antagonist oral anticoagulant surveillance program across all 20 regions of Italy. The study population comprises consecutively screened, consenting patients with NVAF naïve to and newly treated with rivaroxaban for stroke prevention in routine clinical practice. The target enrollment is 800 patients; each patient will be followed for a maximum duration of 24 months. The primary endpoint is the proportion of patients who discontinue rivaroxaban treatment. Secondary endpoints are reasons for rivaroxaban discontinuation, dose changes and reasons for changes, switches to alternative therapies and the reasons for these decisions, and self-reported adherence. Data analyses will be exploratory and descriptive., Conclusion: RITMUS-AF will help to address the limited data in Italian clinical practice on treatment persistence and reasons for drug interruptions in patients with NVAF on rivaroxaban., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V.)

Molecular similarity is an impressively broad topic with many implications in several areas of chemistry. Its roots lie in the paradigm that 'similar molecules have similar properties'. For this reason, methods for determining molecular similarity find wide application in pharmaceutical companies, e.g., in the context of structure-activity relationships. The similarity evaluation is also used in the field of chemical legislation, specifically in the procedure to judge if a new molecule can obtain the status of orphan drug with the consequent financial benefits. For this procedure, the European Medicines Agency uses experts' judgments. It is clear that the perception of the similarity depends on the observer, so the development of models to reproduce the human perception is useful. In this paper, we built models using both 2D fingerprints and 3D descriptors, i.e., molecular shape and pharmacophore descriptors. The proposed models were also evaluated by constructing a dataset of pairs of molecules which was submitted to a group of experts for the similarity judgment. The proposed machine-learning models can be useful to reduce or assist human efforts in future evaluations. For this reason, the new molecules dataset and an online tool for molecular similarity estimation have been made freely available.

Organisms living in icy environments produce antifreeze proteins to control ice growth and recrystallization. It has been proposed that these molecules pin the surface of ice crystals, thus inducing the formation of a curved surface that arrests crystal growth. Such proteins are very appealing for many potential applications in food industry, material science and cryoconservation of organs and tissues. Unfortunately, their structural complexity has seriously hampered their practical use, while efficient and accessible synthetic analogues are highly desirable. In this paper, we used molecular dynamics based techniques to model the interaction of three short antifreeze synthetic peptides with an ice surface. The employed protocols succeeded in reproducing the ice pinning action of antifreeze peptides and the consequent ice growth arrest, as well as in distinguishing between antifreeze and control peptides, for which no such effect was observed. Principal components analysis of peptides trajectories in different simulation settings permitted to highlight the main structural features associated to antifreeze activity. Modeling results are highly correlated with experimentally measured properties, and insights on ice-peptide interactions and on conformational patterns favoring antifreeze activity will prompt the design of new and improved antifreeze peptides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A detailed Valence Bond-Spin Coupled analysis of a series of halogenated molecules is here reported, allowing to get a rigorous ab initio demonstration of the qualitative models previously proposed to explain the origin of halogen bonding. The concepts of σ-hole and negative belt observed around the halogen atoms in the electrostatic potential maps are here interpreted by analysis of the relevant Spin Coupled orbitals., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Strongyloides stercoralis is a nematode causing strongyloidiasis, more frequent in immigrants and in travelers coming from tropical and subtropical areas. Infection is usually asymptomatic, frequently associated with eosinophilia. Immunocompromised patients are at high risk of developing hyperinfection syndrome (HI) or dissemination (SD), life threatening complications. Diagnosis of strongyloidiasis is firstly based on larvae isolation in stool samples; specific therapy involves the use of ivermectin as first choice and albendazole as second choice. We describe two cases of strongyloidiasis. The first one is a disseminated strongyloidiasis occurred in an Ecuadorian male on corticosteroid therapy for nephrotic syndrome due to focal segmental glomerulosclerosis, successfully treated with ivermectin; the second one involves another Ecuadorian male affected by acute kidney failure and nephrotic syndrome in IgA nephropathy with a diagnosis of chronic strongyloidiasis performed before starting the immunosuppressive treatment. The timing of treatment with ivermectin has allowed the complete eradication of the parasite before starting steroid and mycophenolate mofetil therapy, preventing the occurrence of a disseminated infection. Epidemiological data show us how strongyloidiasis is rising at our latitude because of increased number of migrants and travelers coming from endemic areas. So we must always exclude asymptomatic strongyloidiasis before prescribing a steroid or immunosuppressive therapy, in order to avoid developement of disseminated and often fatal disease.

Videolaparoscopic surgery exposes the abdominal organs to the mechanical effect of pneumoperitoneum at pressure values between 12 and 15 mm Hg, which are considered safe. Nevertheless, experimental data have shown that this pressure range can represent a hemodynamic risk factor as it may induce a decrease in the venous return to the right ventricle, a decrease in cardiac output, and activation of the sympathetic nervous system and renin angiotensin system. We report two cases of acute renal failure that occurred soon after videolaparoscopy in young female patients without any evidence of ongoing renal disease. Patient A was 29 years old and was submitted to videolaparoscopic surgery in a follow-up program after surgical treatment of ovarian cancer; patient B was 15 years old and was submitted to the surgical removal of a monolateral ovarian cyst. In neither of the cases was it necessary to perform hemodialysis. Patient A underwent a renal biopsy under ultrasound guidance; optic microscopy showed only in ra- and extraglomerular capillary congestion. In both cases the acute renal failure resolved completely and the patients where discharged with normal renal function. Taking in to account that normal renal venous pressure levels are around 4 mmHg we think that a) a 15 mmHg pneumoperitoneum may represent a risk factor during videolaparoscopic surgery mainly if the patient's extracellular volume is not properly expanded; b) administration of nonsteroidal anti-inflammatory drugs in order to prevent surgical pain may inhibit vasodilatory prostaglandin availability; c) onset of oliguria during the surgical procedure suggests that extracellular volume expansion is required.

A 168-bp amplification product was obtained in RT-PCR experiments using a degenerate oligonucleotide designed on a five-amino acid sequence of IN, a 7-kDa protein, previously characterized as a PKC inhibitor. It was included in the coding ORF of the 1530-bp-long IMAGE clone ID 38900 (accession numbers R51337 and R51448) that produces a translation product of 6.5 kDa. The translation of the ORF conceptual reading frame allowed the preparation of the synthetic protein PKI55, which was found to inhibit and degrade both untreated nPKC d isozymes and activated cPKC isozymes. The PKI55 gene is localized in chromosome 2q35. The Repeat Maskers output showed a 533-bp-long LTR32/ERVL segment that included the PKI55 coding sequence and a complete regulatory region. The coding sequence and the structure of PKI55 were detected in a brain cDNA of Macaca fascicularis (diverged from human lineages about 25 Myr ago). Three other human genes with over 60% identities with PKI55 were identified in three different loci (i.e., chromosomes 10, 15, and 20.) Synthesis of PKI55 was stimulated by PKC activation. A feedback loop of inhibition is established. When the PKCs are overactivated, PKI55 induces degradation of the enzyme and prevents the isozyme overexpression implicated in a number of important diseases including cancer, diabetes, and disorders of the immune system. The presence of the PKI55 sequence in Macaca fascicularis as well as in human chromosomes 10, 15, and 20 indicates a selective advantage for the PKI55 sequence and the adaptive value of the feedback mechanism.

Protein kinase C (PKC) involvement in ischemia-induced neuronal damage has been investigated in superfused rat cerebral cortex slices submitted to 15 min of oxygen-glucose deprivation (OGD) and in primary cultures of rat cortical neurons exposed to 100 microM glutamate (GLU) for 10 min. OGD significantly increased the total PKC activity in the slices, mostly translocated in the particulate fraction. After 1 hr of reperfusion, the total PKC activity was reduced and the translocated fraction dropped by 84% with respect to the control. Western blot analysis of OGD samples showed an increase in total beta(2) and epsilon PKC isoform levels. After reperfusion, the total levels of alpha, beta(1), beta(2) and gamma isoforms were significantly reduced, whereas the epsilon isoform remained at an increased level. Endogenous GLU release from OGD slices increased to about 15 times the basal values after 15 min of oxygen-glucose deprivation, and to 25 and 35 times the basal level in the presence of the PKC inhibitors staurosporine (0.1 microM) and bisindolylmaleimide (1 microM), respectively. Western blot analysis of GLU-treated cortical neurons showed a significant decrease only in the total level of beta(2) isoforms. Cell survival was reduced to 31% in GLU-treated neuronal cultures; PKC inhibitors were not able to modify this effect. These findings demonstrate that the cell response to OGD and GLU involves PKC in a complex way. The net role played by PKC during OGD may be to reduce GLU release and, consequently, neurotoxicity. The isoforms beta(2) and epsilon are affected the most and may play a significant role in the mechanisms underlying neurotoxicity/neuroprotection., (Copyright 2002 Wiley-Liss, Inc.)

One of the complications of arteriovenous fistulas in chronic hemodialyzed patients is the onset of an aneurysm which can be at risk of rupture. Traditional surgical repair is not always feasible and may not be successful in these cases, leading therefore to the loss of a functioning vascular access and requiring in any case the temporary use of a central venous catheter to allow regular hemodialysis sessions. We applied to this kind of aneurysm the same experience developed in the management of major arterial aneurysms and we considered endografting repair a good alternative in this case. In this paper we present the successful treatment of an arteriovenous fistula aneurysm using that technique. A distal radio-cephalic arteriovenous fistula in one of our patients presented an aneurysm with high risk of rupture. The endografting repair with percutaneous insertion of a WallgraftTM endoprosthesis was well tolerated and the vascular access could be used the day after, without the need for a central venous catheter insertion.

Unlabelled: Seroma is one of the most frequent complications of PTFE vascular grafts and its etiology is still unclear., Case Report: A 51 year-old male on regular dialytic treatment for seven years underwent the surgical implantation of a vascular prosthesis of homologous safena due to the thrombosis of his native artero-venous fistula. Several years earlier the patient had suffered the amputation of the left forearm because of electric shock. A few months later the vascular prosthesis was replaced with a PTFE vascular graft as a result of aneurysm formation and thrombosis. During the following days a non pulsating swelling occurred near the arterial anasto-mosis. Ultrasonography, doppler sonography and aspiration confirmed the diagnosis of seroma and it was surgically removed. Some weeks later a new seroma was observed in the same site and associated with a skin ulcer. A new surgical removal had no benefit and about one month later a perigraft collection was found along with signs of bacterial infection. For this reason the patient underwent the surgical excision of the PTFE graft and a vascular access was warranted by placing a Tesio TM catheter. Usually surgery is considered mandatory in seromas larger than 2 cm in diameter and showing continuous growth. In our patient the poor vascular status might have suggested a more conservative management even with a seroma diameter of about 7 cm. Nevertheless the high risk of systemic infection prompted us to remove the PTFE graft.

Sclerosing encapsulating peritonitis (SEP) is a serious complication of long-term continuous ambulatory peritoneal dialysis (CAPD), very likely related to a persisting expression of the transforming growth factor beta1 (TGFbeta1) gene on peritoneal mesothelial cells. We report the case of a 67-year-old uremic woman who developed SEP eight years after being placed on CAPD, complicated by eight episodes of bacterial peritonitis. CAPD was therefore stopped and the patient transferred to hemodialysis. The diagnosis of SEP was confirmed by physical findings (vomiting, abdominal pain with palpable mass, ileus, cachexia) and CT data. The patient was treated with tamoxifen (10 mg/day) for three months, and gradually recovered, a subsequent CT showing a significant reduction of the thickness of peritoneal and intestinal loops. Tamoxifen probably interferes with TGFbeta1 and may be useful in the treatment of this CAPD complication.

Anti-HLA class I monoclonal antibody 01.65 inhibits the proliferative response of PHA-activated human T lymphocytes from peripheral blood mononuclear cells. The recruitment rate in the cell cycle is slack and the G1 and S phases are prolonged. Among the early events after PHA activation, only the calcium-dependent PKC activity appears to be modified: particulate PKC is completely depleted while cytosolic residual PKC is reduced by 80% after MAb 01.65 treatment. We have carried out in greater detail the study of c-myc gene regulation by MAb 01.65 and the results are as follows: (i) c-myc RNA transcription is normally initiated and finished, suggesting a post-transcriptional regulation of c-myc gene expression; (ii) no alteration in c-myc mRNA stability has been documented; (iii) steady-state levels of c-myc mRNA expression by Northern blot analysis and PCR amplification are decreased in the cytoplasmic compartment, while in the nuclear compartment they appear to be increased. Nuclear accumulation of mature mRNA after MAb 01.65 and PKC inhibitor (H7 and StSp) treatment appears to be the most probable mechanism involved. The possible implications of this are discussed.

Neutrophil accumulation and the consequent production of oxygen-derived free radicals are involved in the pathogenesis of Ischemia-Reperfusion syndrome. In this study we investigated whether a treatment with Vitamin E, which has antioxidant properties, could attenuate the tissue damage by interfering with the influx of neutrophils within the ischemic and reperfused human skeletal muscle. To this purpose, patients undergoing aortic cross-clamping during the surgical repair of aortic abdominal aneurysm were studied as a model of ischemia-reperfusion of the lower limb muscles. Muscle biopsies from the right femoral quadriceps of patients not receiving and receiving Vitamin E pretreatment before surgery were taken: a) after the induction of anaesthesia, as control samples, and b) after a period of ischemia followed by 30 min of reperfusion. The tissue samples were either routinely processed for morphological study and immunohistochemical analysis to detect an altered expression of specific endothelial adhesion proteins, such as E-selectin and ICAM-1. The results obtained showed that Vitamin E administration was able to prevent the accumulation of neutrophils within the ischemic and reperfused muscle. This beneficial effect of Vitamin E was due to its ability to hinder the expression of E-selectin and ICAM-1, molecules known to increase the adhesiveness of endothelium to circulating neutrophils. After treatment with Vitamin E a marked attenuation of the reperfusion injury was also evident. In conclusion, Vitamin E treatment may be considered a valuable tool for protection against the ischemia-reperfusion damage of human skeletal muscle.

Purpose: The biochemical and morphological alterations induced in lower limb skeletal muscle by ischemia-reperfusion (I-R) during aortic surgery and the effect of vitamin E pretreatment were investigated., Methods: Two groups of patients undergoing aortic aneurysm resection, one untreated and one treated with vitamin E, were examined. Quadricep muscle biopsies were taken after induction of anesthesia, at the end of ischemia, and after reperfusion. The malondialdehyde (MDA) content and morphology of biopsies were examined to assess peroxidative processes., Results: Ischemia did not induce an increase in MDA content but did increase neutrophil infiltration in muscle fibers of untreated patients. Reperfusion led to a significant increase in MDA content and to intermyofibrillar edema and mitochondrial swelling. The MDA content was not increased during ischemia and neutrophil infiltration was minimal in vitamin E treated patients. At reperfusion, the MDA content, the ultrastructural injuries and neutrophil infiltration were significantly reduced by the treatment., Conclusions: Vitamin E is effective in reducing the oxidative muscle damage occurring after a period of I-R.

Background: A new intubating transilluminated device (Trachlight) has been recently proposed as an alternative to tracheal intubation with direct laryngoscopy., Objective: 1) To evaluate Trachlight device in orotracheal intubation and to assess its operation and complications. 2) To compare the time consumption of transillumination intubation in respect to direct laryngoscopy on the same patients., Methods: The first study was performed on 50 patients undergoing elective surgery and submitted to Trachlight intubation alone; speed of intubation, number of attempts and all complications were recorded and related to Mallampati classes. In the second study 16 patients undergoing to elective surgery were enrolled. Each patient was classified according to both the Mallampati classes and the Cormack classes. Each patient was submitted to two tracheal intubations: the first with the Trachlight and the second with conventional direct laryngoscopy performed by the same anesthesiologist. The time to intubation and the number of attempts were recorded and related to the Mallampati and Cormack classes., Results: In the first study time of intubation with Trachlight was 20.93 +/- 13.02s (mean +/- SD) without statistical differences in respect to the Mallampati classes. In the second study the times to intubation were without any statistical difference independently of the technique of intubation and of the Mallampati or Cormack classes., Conclusions: Orotracheal intubation using Trachlight appears to be an effective and easy to learn technique, being also easy, safe and fast to carry out. The comparison with direct laryngoscopy showed the same speed and effectiveness even on patients with difficult intubation.

Only recently, in our laboratory of experimental surgery, we started with a protocol for orthotopic liver transplantation (OLT) in a pig model. This was felt as mandatory for experimental purposes as well as for future clinical applications at our center. We report herein our own experience with 41 OLTx. Intraoperative "lethal" complications occurred in up to 32% (14/41) whereas postoperative complications occurred in the remainders at different intervals of time with a maximum survival of 30 days. No attention was paid to prevent rejection-infection episodes. The main cause of death was the primary non-function (PNF) or dis-function (PDF) manifested either intra or postoperatively in 16 out the 41 OLTx (39%). Intraoperative technical errors accounted for up to 9% (4/41 OLTx). Acute hemorrhage gastritis and gastric perforations occurred postoperatively in 6 animals (14%) and represent one of the peculiar aspects of OLT in pig model.

Membranous glomerulonephritis is the most common glomerular disease associated with malignancy, the association of minimal change glomerulopathy with solid tumor is still uncommon. We report a 72-year-old man with nephrotic syndrome due to minimal change glomerular disease; an accurate seek of underlying malignancy revealed a cecum adenocarcinoma. We had a complete remission of nephrotic syndrome after surgery of carcinoma.

Toluene diisocyanate (TDI) is the most common cause of occupational asthma in western countries. The aim of this study was to investigate whether genetic factors are involved in toluene diisocyanate-induced asthma. We studied the frequency of human leucocyte antigen (HLA) class II genetic markers in three groups of subjects: 1) subjects with TDI-induced asthma (n = 30); 2) exposed subjects with no history of TDI-induced asthma (n = 12); and 3) normal subjects not exposed to TDI (n = 126). Venous blood samples were collected from the three groups and the polymorphic second exon of DQA and DQB genes was amplified by the polymerase chain reaction (PCR) method. Evaluation of HLA class II gene products in TDI-induced asthma cases showed a positive association with HLA-DQB1 * 0503 and a negative association with HLA-DQB1 * 0501 alleles, which differed at residue 57 for a single amino acid, i.e. aspartic acid in DQB1 * 0503 and valine in DQB1 * 0501. No significant difference was found in the distribution of DQA1 alleles between asthmatics and controls. Our results confirm the hypothesis that HLA-DQB1 * 0503 has a role in conferring susceptibility to TDI-induced asthma and that residue 57 of HLA-DQB1 is a potentially critical location.

We describe a female patient with Vohwinkel syndrome (mutilating palmoplantar keratoderma), who in addition showed cleft lip and palate, microcephaly, facial asymmetry, and other anomalies.

Stimulation by platelet-derived growth factor (PDGF) is known to increase the number of IGF-I binding sites in cells in culture. We show here that PDGF also increases the levels of IGF-1 receptor mRNA. Using cell lines stably transfected with an expression plasmid in which the reporter luciferase gene is under the control of the rat IGF-1 receptor gene promoter, we find that PDGF increases the activity of this promoter. A short IGF-1 receptor gene promoter, comprising about 100 base pairs of the sequence immediately upstream of the initiation of transcription site, is sufficient for a response to the stimulatory action of PDGF. These results suggest that an increase in RNA levels and in promoter activity may play an important role in the increase in IGF-1 receptor levels that occurs after stimulation by PDGF.

A peptide inhibiting either corpuscolate or purified PKC has been identified from microsomes of PHA-activated human PBMC but it is not detectable in microsomes of resting PBMC. The peptide was obtained from a microsomal preparation in an oligomeric form that could be transformed into a monomeric form by beta-MSH. The active peptide (IN) was retained on a PC-11 chromatographic column and could be eluted with NaCl. IN is ineffective on PKC-dependent protamine phosphorylation of protamine and on Ca2+ and phospholipid-independent activity generated by mild hydrolysis with trypsin of PKC. Ca2+ binding is permissive for IN activity. IN inhibits particulate PKC in PHA-activated PBMC, but is ineffective after TPA activation. All these data indicate that IN acts at the regulatory domain of PKC.

Blood lead corrected for hematocrit (PbC) was measured in 115 hemodialysis (HD) patients. Information was collected with a questionnaire about personal and environmental factors thought to influence blood Pb levels. HD patients had significantly higher mean blood Pb than healthy subjects (p < 0.001). A non-negligible percentage of the HD population (13%) had values over 30 micrograms/dl, the threshold for risk in occupational exposure, and 4% over 40 micrograms/dl which reflects Pb intoxication. No association was found between sex, age, duration of HD and PbC. The prevalence of high diastolic blood pressure was associated with PbC over 30 micrograms/dl (p < 0.01). Also, at blood Pb levels generally considered as 'nontoxic' (less than 40 micrograms/dl), we found a low correlation with diastolic blood pressure (r = 0.19, p = 0.049). A correlation was found between PbC and parathyroid hormone (r = 0.22, p = 0.01) and between PbC and mean corpuscular volume (r = -0.21, p = 0.02). The patients with individual risk factors (smoke, alcohol consumption and alkyl Pb from air contamination) had PbC levels higher than patients without (p = 0.001). The patients with environmental risk factors (professional exposure, tap water consumption and older houses) had PbC levels higher than patients without (p = 0.01). Patients with past occupational exposure had the highest mean PbC levels (34.1 micrograms/dl = 1.65 nM/ml).

It is known that anti-HLA Class I antibodies inhibit the proliferative response of PHA-activated T-lymphocytes. We found that plastic- or sepharose-linked anti-HLA Class I monoclonal antibody 01.65 does not inhibit either [3H]Thymidine incorporation or recruitment in the cell cycle, nor does it reduce the expression of c-myc mRNA and the membrane expression of Interleukin-2 Receptor and Transferrin Receptor. Furthermore, particulate Protein Kinase C is not affected by anchored anti-HLA Class I monoclonal antibody 01.65. We suggest that anti-HLA Class I monoclonal antibody may act through crosslinking or internalization of HLA Class I antigens.

Studies of the mode of inheritance of affective disorders have been reviewed. The overall picture which emerges does not seem to involve specific modes of inheritance. Linkage studies based on the single gene hypothesis, support X-linkage for a bipolar variant, as well as possible linkage to chromosomes 6 and 11. The more recent approach of linkage studies using large numbers of RFLP markers scattered throughout the genome looks promising, though it may still give rise to misinformation. Several confounding factors have been suggested such as genetic and phenotypic heterogeneity, as well as the lack of well defined diagnostic criteria.

Anti-HLA class I monoclonal antibody (mAb) 01.65 inhibited phytohaemagglutinin (PHA)-induced human lymphocyte proliferation. The inhibitory effect was inversely correlated to the strength of the proliferative response. It was increased when lymphocytes were stimulated with suboptimal doses of PHA but it disappeared with supraoptimal doses. Proliferation inhibition was achieved by prolonging the cell cycle time and by slowing down its recruitment rate. The former effect was not restricted to the G1-phase but also included the S phase. These results support the idea that HLA class I molecules are important in the PHA-induced proliferation of human T-lymphocytes.

We identified a subgroup of ataxia-telangiectasia (AT) patients (2 sibs and 1 unrelated case) characterized by typical clinical manifestations of the disease and cellular radiosensitivity intermediate between classical AT and normal subjects. Our data and a literature review of the intermediate radiosensitivity AT cases show that radioresistant DNA synthesis, cellular radiosensitivity (measured in terms of survival and chromosome breakage), and the clinical hallmarks behave independently. This raises a number of interesting questions about the correlation between radiobiological and clinical features, and about the nature of the AT gene(s).

HLA class I antigens seem to be involved in the proliferative response of PHA-activated human T-lymphocytes. We have previously reported that the treatment of PHA-activated peripheral blood mononuclear cells (PBMC) with an anti-HLA class I monoclonal antibody, 01.65, (i) inhibits the tritiated thymidine incorporation, (ii) inactivates cytosolic protein kinase C (PKC) and (iii) causes an increase in the duration of the cell cycle. Northern Blot kinetic analysis of c-fos, c-myc, cdc2, IL-2R, c-myb, ODC, TK and H3, from 10 minutes to 120 hours, was performed in MAb 01.65 treated cultures. We found that the expression of four genes (c-myc, IL-2R, cdc2 and TK) was depressed 24 hours after PHA stimulation.

N-N-Staurosporine (STAR) inhibits in a dose dependent manner Tritiated-Thymidine (3H-TdR) incorporation in phytohemagglutinin (PHA) activated Peripheral Blood Mononuclear Cells (PBMC) treated with anti-HLA class I monoclonal antibody (MAb) 01.65 and its effect results competitive with MAb 01.65. Cytosolic and particulate Protein Kinase C (PKC) have been studied. Only when PKC particulate activity is no more detectable, the effect of STAR on 3H-TdR incorporation is evident.

Monoclonal anti HLA class I antibodies inhibit the proliferative response of PHA-stimulated T lymphocytes. We studied the effects of MAb 01.65 anti-HLA class I on c-fos, c-myc and IL-2R mRNA expression. We found that MAb treatment does not modify either c-fos mRNA levels observed after 10 minutes to 3 hrs or the early c-myc mRNA expression revealed after 1 to 6 hrs, but decreases the intensity of autoradiographic signals of late c-myc and IL-2R mRNA expression. Since we had previously ascertained that MAb 01.65 treatment induces a decrease in PKC enzymatic activity after few minutes, the correlation of that result with the data presented in this paper will be discussed.

Cytosolic and Particulate Protein Kinase C has been studied in Peripheral Blood Mononuclear Cells activated with 12-O-Tetradecanoyl phorbol 13-acetate and treated with the anti-HLA Class I Monoclonal Antibody 01.65. No effects on the cellular distribution of PKC activity nor to the proliferative response has been found. In phytohemagglutinin stimulated PBMC cultures treated with MoAb 01.65 total PKC activity depletion and 3H-Thymidine incorporation inhibition has been found. In PBMC cultures activated with both PHA and TPA, the proliferative response was similar to cultures activated with PHA alone, while the PKC cellular distribution was similar to the one detected in TPA stimulated cultures. Addition of the MoAb 01.65 was ineffective on both PKC activity and 3H-Thymidine incorporation. These data indicate that anti-HLA Class I MoAb induced 3H-Thymidine incorporation inhibition may be related to low levels of PKC activity.

The monomorphic anti-HLA Class I monoclonal antibody 01.65 inhibits the incorporation of tritiated thymidine ([3H]TdR) in Phytohemagglutinin (PHA)-activated human T lymphocytes. Our data indicate that 01.65 affects the average duration of the cell cycle by increasing the length of the early S subphase. As a consequence of the increase in the doubling time of the cell population, the absolute number of cells at harvesting time was reduced in 01.65-treated cultures compared to that of untreated cultures. The lengthening of the S-phase and the decrease in the cell number can together quantitatively account for the reduction of [3H]TdR incorporation observed in 01.65-treated cultures.

Anti HLA Class I Monoclonal Antibody depletes Protein Kinase C (PKC) to 20% of control value in PHA activated human T cells. The effect is reversible: in 24 hours the enzymatic activity returns to 58% of control value. Removal of antibody from the culture medium increases the rate of recovery. Implications of this finding for the modulation by HLA Class I antigens of the proliferative response of T cells to lectins are discussed.

Peripheral lymphocytes of three Fanconi's anemia (FA) patients and of five heterozygotes have been tested for their susceptibility to chromosomal breakage and sister chromatid exchange (SCE) induction by diepoxybutane (DEB). As previously shown, DEB dramatically increases the chromosomal breakage level in both homozygotes and heterozygotes. Slightly, but significantly, reduced spontaneous levels of SCE were found in cultures from FA patients and FA gene carriers as compared with controls. SCE rates were not enhanced in lymphocytes grown in the presence of DEB, irrespective of the time at which it had been added to the culture, and were comparable in cells of FA patients and FA heterozygotes. This was in contrast with SCE rates in control cells, which showed increases positively related to the length of DEB treatment.

Cytoplasmic protein kinase C (PKC) has been studied in phytohemagglutinin (PHA) activated peripheral blood mononuclear cells (PBMC) and macrophage depleted E+ cell culture. Within 10' after contemporanous addition of PHA and anti HLA class I monoclonal antibody 01.65 (MoAb) PKC is depleted in both cell types. Enzyme activity recovers in the following hours however at 72 hours is at control values in E+ cultures while in PBMC cultures it is still depleted at 68% of the control. Anti HLA class I MoAb induced tritiated lymidine (3H-TdR) incorporation inhibition appears to be related to low levels of PKC activity.

HLA phenotypes of 64 Italian pediatric patients with celiac disease (CD) were compared with those of a group of healthy controls. DR3 and DR7 are significantly increased as reported in other populations. In addition an increase of heterozygotes DR5/DR7 was observed in our patients. The Hardy-Weinberg distribution in the patients group shows a disequilibrium due to the genotype DR5/DR7. Our data confirm that more than one HLA gene product is associated with CD: one with DR3 and the other with DR7.

In the context of a multidisciplinary study program whose purpose is to investigate the genetic aspects of Huntington's Chorea (HC), the authors conducted an epidemiological descriptive research extended to the population residing in the province of Ferrara in a time period including the years from 1971 to 1987. On December 31st, 1987 we estimated a prevalence rate of 1.89 cases of HC per 100,000 inhabitants; in the years 1971-1987 the incidence rate was of 0.11 per 100,000/year and the mortality rate of 0.06 per 100,000/year. In the last years considered for the study, the incidence and the prevalence showed a relative increase indicating that HC still exists in the ferrarese population, despite a greater public awareness. With the aim to organize preventive actions and to reach the preclinical diagnosis of the disease we singled out 83 subjects at risk the study area.

The cytogenetic effect of the DNA polymerase alpha inhibitor aphidicolin (APC) at a dose which did not affect cell cycle progression was determined in normal and Fanconi's anemia (FA) lymphocytes. APC enhanced sister-chromatid exchange (SCE) levels by about twice both in control and FA cells, while the yields of chromosome breakage increased up to 20 times in normal lymphocytes and 4 times in FA cells. APC did not act synergistically with the bifunctional alkylating diepoxybutane in terms of SCE either in normal or in FA lymphocytes. However, chromosome aberrations in cultures from normal subjects were much more than expected by an additive mode of action.

Two unrelated patients carrying imbalances involving the long arm of chromosome 6 are described. In the first trisomy 6q21 leads to qter had segregated from a maternal translocation t(6;16)(q15;q24). The clinical data of the proposita are compared with those of three other published cases. A partial 6q trisomy syndrome is postulated characterized by: growth deficiency of prenatal onset, psychomotor retardation, craniofacial abnormalities (microcephalia, hypertelorism, downward slanting palpebral fissures, flattened nasal bridge, long philtrum, hypoplastic perioral features, large jaw resulting in a round appearance of the face, receding chin, malformed ears) and dysmorphic extremities (contractures of limbs due to short flexor tendons, hypoplastic fingers, toes and nails). In the second case, monosomy 6q221 leads to qter resulted from a de novo rearrangement and was responsible for mental retardation and facial dysmorphism (reduced biparietal diameter, hypotelorism, absent eyebrows, prominent nose, ptosis, receding chin, dysmorphic ears). Studies of HLA and PGM3 segregation showed normal inheritance patterns and ruled out the location of these genes in bands 6q221 leads to qter.

Balb/c mice were immunized with a human B-lymphoblastoid cell line typed HLA-A3, B7. The splenocytes of the immunized mice were fused with a murine myeloma. Supernatants of the cultures were screened against the immunizing cell line in fluorochromasia. Positive cultures were expanded and cloned. One of the clones, X 15.4, was expanded and brought to ascites in Balb/c mice. Monoclonality of the antibody X 15.4, which belongs to the class IgM and immunoprecipitates a molecule of 44000 daltons, was demonstrated by isoelectric focusing. By complement dependent cytotoxicity the ascites only reacted with the lymphocytes of all HLA-A3 individuals from a panel of 146 donors, showing no crossreactions. X 15.4 appears to be one of the very rare xenomonoclonal antibodies suitable for HLA typing.

Report is given of a mentally retarded and dysmorphic patient with a partial monosomy 8q, resulting from a de novo translocation t(4;8)(q13;q213). Oetermination of erythrocyte glutathione reductase (E-GSR) activity in the proposita shows activity in the normal range. Previous evidence for of the assignment of E-GSR locus to the short arm of chromosome 8 is confirmed.

One hundred and twenty-one Italian children with coeliac disease (CD) have been compared with a control population from the same geographical area for the distribution of HLA-DR and DQ antigens. The pattern of an increase in DR3, DR7, and of heterozygotes DR5/7 was associated with an excess of heterozygotes DQw2/DQw3 in the CD population. These findings suggest that epitopes determined by specific combinations of DQ alpha and beta chains (combinatorial determinants) predispose to the disease.

The hybridoma technique was used to produce a mouse monoclonal antibody, designated as XI 21.4, which belongs to the IgG2a class. It is active in complement-dependent cytotoxicity and detects a B-cell antigenic determinant associated with DR1, DR4, DRw10, and, possibly, DRw9. Microfingerprinting of the immunoprecipitate from a homozygous DR4 cell line shows a typical alpha DR pattern and a beta pattern coinciding with that of DR4 molecules.