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The production of dense samples produced by laser powder bed fusion (LPBF) is mainly determined by the choice of the best combination of construction parameters. Parameter optimization is the first step in the definition of an LPBF process for new alloys or systems. With this goal, much research uses the single scan track (SST) approach for a preliminary parameter screening. This study investigates the definition of a computer-aided method by using an automatic on top analysis for the characterization of SSTs, with the aim of finding ranges of laser power and scan speed values for massive production. An innovative algorithm was implemented to discard non-continuous scans and to measure the SSTs quality using three regularity indexes. Only open source software were used to fine tune this approach. The obtained results on Al4Cu and AlSi10Mg realized with two different commercial systems suggest that it is possible to use this method to easily narrow the process parameter window that allows the production of dense samples.

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: β = -0.001 (-0.008, 0.006); females: β = -0.004 [-0.015, 0.007]; males: β = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Additive manufacturing is a key enabling technology in the manufacture of highly complex shapes, having very few geometric limitations compared to traditional manufacturing processes. The present paper aims at investigating mechanical properties at cryogenic temperatures for a 316L austenitic stainless steel, due to the wide possible cryogenic applications such as liquid gas confinement or superconductors. The starting powders have been processed by laser powder bed fusion (LPBF) and tested in the as-built conditions and after stress relieving treatments. Mechanical properties at 298, 77 and 4.2 K from tensile testing are presented together with fracture surfaces investigated by field emission scanning electron microscopy. The results show that high tensile strength at cryogenic temperature is characteristic for all samples, with ultimate tensile strength as high as 1246 MPa at 4.2 K and 55% maximum total elongation at 77 K. This study can constitute a solid basis for investigating 316L components by LPBF for specific applications in cryogenic conditions.

The aim of this study is to define the process parameters to build components for industrial applications in A357 alloy by Laser Powder Bed Fusion (LPBF) and to evaluate the effects of post-processing heat treatments on the microstructure and mechanical properties in order to obtain the highest hardness and strength. First, process parameters values were defined to obtain full dense components with highest productivity. Then samples were built for microstructural, hardness, and tensile strength investigation in different conditions: as-built, after a stress-relieving treatment, and after a T6 precipitation hardening treatment. For this latest treatment, different time and temperatures for solution and ageing were investigated to find the best in terms of final hardness achievable. It is demonstrated that samples in A357 alloy can be successfully fabricated by LPBF with a density of 99.9% and a mean hardness value achievable of 116 HV0.1, in as-built condition. However, for production purposes, it is fundamental to reduce the residual stresses typical of LPBF. It was shown that a similar hardness value could be obtained after a stress-relieving treatment followed by a proper T6 treatment, together with a coarser but more isotropic microstructure.

The effect of microstructure on the susceptibility to selective corrosion of Alloy 625 produced by laser powder bed fusion (LPBF) process was investigated through intergranular corrosion tests according to ASTM G28 standard. The effect of heat treatment on selective corrosion susceptibility was also evaluated. The behavior was compared to commercial hot-worked, heat treated Grade 1 Alloy 625. The morphology of attack after boiling ferric sulfate-sulfuric acid test according to ASTM G28 standard is less penetrating for LPBF 625 alloy compared to hot-worked and heat-treated alloy both in as-built condition and after heat treatment. The different attack morphology can be ascribed to the oversaturation of the alloying elements in the nickel austenitic matrix obtained due to the very high cooling rate. On as-built specimens, a shallow selective attack of the border of the melt pools was observed, which disappeared after the heat treatment. The results confirmed similar intergranular corrosion susceptibility, but different corrosion morphologies were detected. The results are discussed in relation to the unique microstructures of LPBF manufactured alloys.

Aluminum alloys are key materials in additive manufacturing (AM) technologies thanks to their low density that, coupled with the possibility to create complex geometries of these innovative processes, can be exploited for several applications in aerospace and automotive fields. The AM process of these alloys had to face many challenges because, due to their low laser absorption, high thermal conductivity and reduced powder flowability, they are characterized by poor processability. Nowadays mainly Al-Si alloys are processed, however, in recent years many efforts have been carried out in developing new compositions specifically designed for laser based powder bed AM processes. This paper reviews the state of the art of the aluminum alloys used in the laser powder bed fusion process, together with the microstructural and mechanical characterizations.

Being able to replicate scientific findings is crucial for scientific progress 1-15 . We replicate 21 systematically selected experimental studies in the social sciences published in Nature and Science between 2010 and 2015 16-36 . The replications follow analysis plans reviewed by the original authors and pre-registered prior to the replications. The replications are high powered, with sample sizes on average about five times higher than in the original studies. We find a significant effect in the same direction as the original study for 13 (62%) studies, and the effect size of the replications is on average about 50% of the original effect size. Replicability varies between 12 (57%) and 14 (67%) studies for complementary replicability indicators. Consistent with these results, the estimated true-positive rate is 67% in a Bayesian analysis. The relative effect size of true positives is estimated to be 71%, suggesting that both false positives and inflated effect sizes of true positives contribute to imperfect reproducibility. Furthermore, we find that peer beliefs of replicability are strongly related to replicability, suggesting that the research community could predict which results would replicate and that failures to replicate were not the result of chance alone.

This experimental work is aimed at studying the effect of microstructural modifications induced by post-processing heat treatments on the corrosion behavior of silicon-aluminum alloys produced by means of laser powder bed fusion (LPBF). The manufacturing technique leads to microstructures characterized by the presence of melt pools, which are quite different compared to casting alloys. In this study, the behavior of an AlSi10Mg alloy was evaluated by means of intergranular corrosion tests according to ISO 11846 standard on heat-treated samples ranging from 200 to 500 °C as well as on untreated samples. We found that temperatures above 200 °C reduced microhardness of the alloy, and different corrosion morphologies occurred due to the modification of both size and distribution of silicon precipitates. Selective penetrating attacks occurred at melt pool borders. The intergranular corrosion phenomena were less intense for as-produced specimens without heat treatments compared to the heat-treated specimens at 200 and 300 °C. General corrosion morphologies were noticed for specimens heat treated at temperatures exceeding 400 °C.

The mechanical properties and biocompatibility of titanium alloy medical devices and implants produced by additive manufacturing (AM) technologies - in particular, selective laser melting (SLM), electron beam melting (EBM) and laser metal deposition (LMD) - have been investigated by several researchers demonstrating how these innovative processes are able to fulfil medical requirements for clinical applications. This work reviews the advantages given by these technologies, which include the possibility to create porous complex structures to improve osseointegration and mechanical properties (best match with the modulus of elasticity of local bone), to lower processing costs, to produce custom-made implants according to the data for the patient acquired via computed tomography and to reduce waste.

The aim of this review is to analyze and to summarize the state of the art of the processing of aluminum alloys, and in particular of the AlSi10Mg alloy, obtained by means of the Additive Manufacturing (AM) technique known as Selective Laser Melting (SLM). This process is gaining interest worldwide, thanks to the possibility of obtaining a freeform fabrication coupled with high mechanical properties related to a very fine microstructure. However, SLM is very complex, from a physical point of view, due to the interaction between a concentrated laser source and metallic powders, and to the extremely rapid melting and the subsequent fast solidification. The effects of the main process variables on the properties of the final parts are analyzed in this review: from the starting powder properties, such as shape and powder size distribution, to the main process parameters, such as laser power and speed, layer thickness, and scanning strategy. Furthermore, a detailed overview on the microstructure of the AlSi10Mg material, with the related tensile and fatigue properties of the final SLM parts, in some cases after different heat treatments, is presented.

Transmission of Imaging and Data (TRIAD) is a standard-based system built by the American College of Radiology to provide the seamless exchange of images and data for accreditation of clinical trials and registries. Scripts of structures' names validation profiles created in TRIAD are used in the automated submission process. It is essential for users to understand the logistics of these scripts for successful submission of radiation therapy cases with less iteration., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

On page 3712, E. Fantino, A. Chiappone, and co-workers fabricate conductive 3D hybrid structures by coupling the photo-reduction of metal precursors with 3D printing technology. The generated structures consist of metal nanoparticles embedded in a polymer matrix shaped into complex multilayered architectures. 3D conductive structures are fabricated with a digital light-processing printer incorporating silver salt into photocurable formulations., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Coupling the photoreduction of a metal precursor with 3D-printing technology is shown to allow the fabrication of conductive 3D hybrid structures consisting of metal nanoparticles and organic polymers shaped in complex multilayered architectures. 3D conductive structures are fabricated incorporating silver nitrate into a photocurable oligomer in the presence of suitable photoinitiators and exposing them to a digital light system., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this work, three-dimensional (3D) structured hybrid materials were fabricated combining 3D printing technology with in situ generation of inorganic nanoparticles by sol-gel technique. Those materials, consisting of silica nanodomains covalently interconnected with organic polymers, were 3D printed in complex multilayered architectures, incorporating liquid silica precursors into a photocurable oligomer in the presence of suitable photoinitiators and exposing them to a digital light system. A post sol-gel treatment in acidic vapors allowed the in situ generation of the inorganic phase in a dedicated step. This method allows to build hybrid structures operating with a full liquid formulation without meeting the drawbacks of incorporating inorganic powders into 3D printable formulations. The influence of the generated silica nanoparticle on the printed objects was deeply investigated at macro- and nanoscale; the resulting light hybrid structures show improved mechanical properties and, thus, have a huge potential for applications in a variety of advanced technologies.

In contemporary society we observe an everlasting permeation of electron devices, smartphones, portable computing tools. The tiniest living organisms on Earth could become the key to address this challenge: energy generation by bacterial processes from renewable stocks/waste through devices such as microbial fuel cells (MFCs). However, the application of this solution was limited by a moderately low efficiency. We explored the limits, if any, of additive manufacturing (AM) technology to fabricate a fully AM-based powering device, exploiting low density, open porosities able to host the microbes, systems easy to fuel continuously and to run safely. We obtained an optimal energy recovery close to 3 kWh m(-3) per day that can power sensors and low-power appliances, allowing data processing and transmission from remote/harsh environments.

Purpose: RTOG 0933 was a phase II trial of hippocampal avoidance during whole brain radiation therapy for patients with brain metastases. The results demonstrated improvement in short-term memory decline, as compared with historical control individuals, and preservation of quality of life. Integral to the conduct of this trial were quality assurance processes inclusive of pre-enrollment credentialing and pretreatment centralized review of enrolled patients., Methods and Materials: Before enrolling patients, all treating physicians and sites were required to successfully complete a "dry-run" credentialing test. The treating physicians were credentialed based on accuracy of magnetic resonance imaging-computed tomography image fusion and hippocampal and normal tissue contouring, and the sites were credentialed based on protocol-specified dosimetric criteria. Using the same criteria, pretreatment centralized review of enrolled patients was conducted. Physicians enrolling 3 consecutive patients without unacceptable deviations were permitted to enroll further patients without pretreatment review, although their cases were reviewed after treatment., Results: In all, 113 physicians and 84 sites were credentialed. Eight physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were approved on the second attempt. Eight sites (9.5%) failed intensity modulated radiation therapy planning on the first attempt; all were approved on the second attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated the eligibility criteria, and 21 (24%) had unacceptable deviations. With feedback, 18 cases were approved on the second attempt and 2 cases on the third attempt. One patient was treated off protocol. Twenty-two cases were reviewed after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had unacceptable deviations., Conclusions: Although >95% of the cases passed the pre-enrollment credentialing, the pretreatment centralized review disqualified 5.7% of reviewed cases, prevented unacceptable deviations in 24% of reviewed cases, and limited the final unacceptable deviation rate to 5%. Thus, pretreatment review is deemed necessary in future hippocampal avoidance trials and is potentially useful in other similarly challenging radiation therapy technique trials., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In this paper, a characterization of an AlSiMg alloy processed by direct metal laser sintering (DMLS) is presented, from the analysis of the starting powders, in terms of size, morphology and chemical composition, through to the evaluation of mechanical and microstructural properties of specimens built along different orientations parallel and perpendicular to the powder deposition plane. With respect to a similar aluminum alloy as-fabricated, a higher yield strength of about 40% due to the very fine microstructure, closely related to the mechanisms involved in this additive process is observed.

TiO(2) nanotube (NT) arrays with different lengths were fabricated by anodic oxidation of Ti foil and free-standing NT membranes were detached by the metal substrate and bonded on the fluorine-doped tin oxide surface implementing an easy procedure. Morphology of the as-grown material and of the prepared photoanode was investigated by means of electron microscopy, deepening the investigation on the thermal treatment effect. Crystalline orientation and exposed surface area were studied by X-ray diffraction and Brunauer-Emmett-Teller measurements, showing suitable characteristics for the application in dye-sensitized solar cells (DSCs). DSCs were assembled employing a microfluidic housing system. The cell performances and the electron transport properties as a function of the tube length, before and after a TiCl(4) treatment, were characterized by I-V electrical measurements, incident photon-to-electron conversion efficiency, electrochemical impedance spectroscopy and open circuit voltage decay. Fitting the impedance spectra with an equivalent circuit, it was possible to obtain information on the electron diffusion properties into the TiO(2) nanotubes. A comparison with the charge transport properties evaluated in nanoparticle-based photoanodes witnesses a noteworthy increase of electron lifetime and diffusion length, yielding an overall power conversion efficiency up to 7.56%.

Sponge-like nanostructured ZnO layers were successfully employed as photoanodes for the fabrication of highly efficient dye-sensitized solar cells. The sponge-like ZnO layers were obtained by room temperature radio-frequency magnetron sputtering deposition of metallic zinc, followed by thermal oxidation treatment in an ambient atmosphere. The porous films show a 3D branched nanomorphology, with a feature similar to natural coral. The morphological and optical properties of these layers were studied through field emission scanning electron microscopy, specific surface area measurements, ultraviolet-visible transmittance and absorption spectroscopy. The sponge-like ZnO film presents a high density of branches, with a relatively high specific surface area value, and fine optical transmittance. The morphology of the porous structure provides a high number of adsorption sites for the anchoring of sensitizer molecules, making it suitable for the fabrication of ZnO-based photoanodes for dye-sensitized solar cells. The light harvesting performance of the sensitized semiconductor was evaluated by current density vs. voltage measurements, incident photon-to-electron conversion efficiency, open circuit voltage decay and impedance spectroscopy. The modelling of the electrical characteristics evidences a higher electron lifetime and a longer charge diffusion length, if compared to standard TiO(2) nanoparticle based photoanodes. For ZnO films with a thickness up to 18 μm, a photoconversion efficiency as high as 6.67% and a maximum value of the incident photon-to-electron collection efficiency equal to 87% at 530 nm were demonstrated.

Background: This report analyzes the adherence to radiation therapy protocol guidelines in contemporary Radiation Therapy Oncology Group (RTOG) gastrointestinal trials. We aim to provide insight into current standards and compliance of radiation therapy field design and administration., Methods: From 1994 to 2006, the Gastrointestinal Cancer Committee of the RTOG initiated and completed 15 phase I-III clinical trials utilizing radiation therapy in the multimodality treatment of gastrointestinal cancers. In each protocol, details for planning and executing radiation therapy were outlined and each protocol contained scoring criteria for these components of radiation therapy, characterized according to per-protocol, variation acceptable and deviation unacceptable. Review of treatment planning and implementation was performed in all studies following therapy completion., Results: Radiation therapy planning and implementation was reviewed in 2309 of 2312 (99.9%) patients. The mean rate of compliance over all for the 15 protocols was 65% (total of the 2309 analyzed patients). The mean variation acceptable rate was 21% whereas the mean deviation unacceptable rate was 5%. The mean "other" rate (no RT given or incomplete RT due to death, progression or refusal) was 8%. Two of the 15 trials (13%) had deviation unacceptable rates >10%. In four studies incorporating pre-treatment review of radiation therapy planning and treatment, compliance with protocol therapy was enhanced., Conclusions: The fidelity of radiation planning and execution detailed in protocol to actual therapy is heterogeneous, with a mean per-protocol rate of 65%. As clinical trials evolve, available technology should permit efficient pre-treatment review processes, thus facilitating compliance to protocol therapy. These analyses should also permit prospective analysis of outcome measures by compliance to therapy., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Over-expression of anti-apoptotic BCL2 has been reported in chronic lymphocytic leukaemia (CLL), but targeting BCL2 alone did not yield appreciable clinical results. However, it was demonstrated that BCL2 inhibitors enhanced the clinical efficacy of chemo and immunotherapeutics. Lenalidomide, an immunomodulator, is clinically effective in CLL and can enhance the anti-CLL effects of CD20 targeting monoclonal antibody, rituximab. Here, we investigated the mechanism of immune-directed killing of lenalidomide in CLL and evaluated if concurrent targeting of CD20 and BCL2 can enhance this effect. In vitro treatment with lenalidomide enhanced the antibody-mediated cellular cytotoxicity (ADCC) directed by rituximab in autologous leukaemic cells. Furthermore, peripheral blood mononuclear cells obtained from patients after treatment with lenalidomide and rituximab showed increased ADCC in vitro versus control (pre-treatment sample). This effect was further enhanced with pre-treatment of tumour cells with AT-101 (a BH3 mimetic that functions as BCL2 antagonist). Our data suggest that AT-101 in combination with lenalidomide can potentially be an effective therapeutic regimen for CLL., (© 2011 Blackwell Publishing Ltd.)

Novel agents have provided a new foundation for multiple myeloma therapies. When combined with other anti-myeloma agents, these compounds significantly enhance clinical efficacy. High-dose steroids are frequently used in anti-myeloma combination regimens; however, the doses employed are often poorly tolerated, especially in patients with concurrent comorbid conditions. We hypothesized that a steroid-independent combination regimen could be developed without significant compromise of efficacy. The availability of such a regimen will be important for patients whose concurrent ailments make them poor candidates for steroid containing anti-myeloma regimens. A phase II single institute, non-randomized clinical trial was conducted to investigate a novel steroid-free three-drug combination of bortezomib (V), pegylated liposomal doxorubicin (D), and thalidomide (T), the VDT regimen. Forty-three newly diagnosed multiple myeloma patients requiring treatment were enrolled on this study. The overall response rate and complete response (CR) + near complete response (nCR) rate was 78% and 35%, respectively. Median time to progression was 29·5 months. Fatigue, rash, neuropathy, constipation and infections were the most common side effects. We concluded that VDT is a tolerable and an effective regimen capable of inducing high response rates and can be employed in patients considered to be poor candidates for steroid-based treatment regimens., (© 2011 Blackwell Publishing Ltd.)

Introduction: Our study was designed to analyze dynamic changes in autonomic tone before the onset of typical sustained atrioventricular nodal reentry tachycardia (AVNRT) in a large group of patients without structural heart disease., Materials and Methods: Twenty-four-hour Holter tapes from 42 consecutive patients (27 men and 15 women; aged 30 + or - 21 years) with several episodes of sustained typical AVNRT were analyzed. The diagnosis was validated by transesophageal electrophysiological study. The time-domain calculated parameters were SDNN, SDANN, rMSSD, pNN50; the frequency-domain parameters were low-frequency power (LF, 0.04-0.15 Hz), high-frequency power (HF, 0.15-0.40 Hz), very low-frequency power (VLF, 0.008 to 0.04 Hz) and LF/HF. The mean values in the hour before the onset of sustained AVNRT were compared with the mean values of 2 hours before and 1 hour after the onset of sustained AVNRT., Results: The mean SDNN, rMSSD, pNN50, HF were significantly decreased during the hour preceding the onset of AVNRT, when compared to the mean values observed during the time periods selected. Instead, the LF values and LF/HF were increased before the onset of sustained AVNRT. No significant change in the VLF and atrial ectopic beats were observed., Conclusion: This study suggests that sustained typical AVNRT episodes are preceded by increase in adrenergic drive.

Background: Acetaminophen (paracetamol-P) is a widely used analgesic-antipyretic drug with no anti inflammatory effects and its rate of adverse hypersensitivity reactions is very low. On the contrary non-steroidal anti-inflammatory drugs (NSAIDs) are commonly involved in side effects. Celecoxib (CE) is a novel drug, with high selectivity and affinity for COX-2 enzyme., Objective: We evaluated the tolerability of CE in a group of patients with documented history of adverse cutaneous reactions to P and to classic NSAIDs., Methods: We studied 29 patients with hypersensitivity to P and classic NSAIDs. The diagnosis of P-induced skin reactions was based on in vivo challenge. The placebo was blindly administered at the beginning of each challenge. After three days, a cumulative dosage of 200 mg of CE in refracted doses was given. After 2-3 days, a single dose of 200 mg was administered. All patients were observed for 6 hours after each challenge, and they were controlled again after 24 hours to exclude delayed reactions. The challenge was considered positive if one or more of the following appeared: erythema, rash or urticaria-angioedema., Results: No reaction was observed with placebo and twenty eight patients (96.5 %) tolerated CE. Only one patient developed a moderate angioedema of the lips., Conclusion: Only one hypersensitivity reaction to CE was documented among 29 P-intolerant patients. Thus, we conclude that CE is a reasonably safe alternative which can be used in subjects who do not tolerate P.

Property comparison models of metaphor comprehension assume that the topic and vehicle terms in metaphors are both understood to be referring to their conventional literal referents. In contrast, the interactive property attribution model (Glucksberg, McGlone, & Manfredi, 1997) assumes that the vehicle is understood to be referring to a metaphoric category that includes the topic's literal referent as a member. A priming paradigm was used to test the implications of these different models. Prior to interpreting a metaphor, participants read (1) the topic or vehicle concept alone, (2) a sentence ascribing a metaphor-relevant property to one concept, or (3) a sentence ascribing a metaphor-irrelevant property to one concept. All of the prime types facilitated metaphor comprehension with the exception of sentences ascribing metaphor-irrelevant properties to vehicles. The failure of these sentences (but not their topic counterparts) to facilitate metaphor comprehension is attributable to their priming an inappropriate literal interpretation of the vehicle term. These results are consistent with the claim that irrelevant information is suppressed during language comprehension (Gernsbacher, 1990) and support the interactive property attribution model.

The authors retrospectively analyse the results achieved in recent years by surgical treatment of 103 malignant primary or secondary liver cancers: (Three patients have been operated on twice at different times for recurrence.) 23 hepatic resections were performed for benign lesions. The operative mortality is very low, the incidence of postoperative complications is minimal, and the survival up to 8 years is rather satisfactory. In all cases we used Ton That Tung's surgical technique, that is, "finger fracture with intraparenchymal ligature of the vasculobiliary pedicles."

Indirect immunofluorescence staining with monoclonal antibodies has shown a differential distribution of HLA-DR, DQ, and DP antigens in normal tissues of nonlymphoid origin. The distribution of HLA-DP antigens is similar to that of HLA-DR antigens, while that of HLA-DQ antigens is more restricted. Malignant transformation of cells of nonlymphoid origin may be associated with the appearance of the gene products of the HLA-D region. HLA-DR antigens appear more frequently than the other two types of HLA class II antigens and HLA-DP antigens more frequently than HLA-DQ antigens. Differential expression of the gene products of the HLA-D region was also found in autologous metastases removed from different anatomic sites from patients with melanoma. The HLA class II phenotype of surgically removed malignant lesions did not correlate with the degree of differentiation of tumor cells and/or with the expression and/or cellular distribution of HLA class I antigens. Furthermore, in melanoma lesions, no relationship was found between the HLA class II phenotype and the expression of 3 membrane bound and 1 cytoplasmic melanoma associated antigen recognized by monoclonal antibodies. The functional significance and the practical implications of the differential expression of the gene products of the HLA-D region by tumor cells are discussed.

Indirect immunofluorescence and immunoperoxidase staining of surgically removed tissues of nonlymphoid origin with monoclonal antibodies to the heavy and light chain of HLA-A,B,C antigens have shown that they have a more restricted tissue distribution than previously assumed. HLA-A,B,C antigens were not detected in brain cortex, cerebellum, sympathetic ganglia, hypophysis, parathyroid gland, thyroid, exocrine pancreas, hepatocytes, sperm, seminiferous tubules, or skeletal or smooth muscle. Malignant transformation of cells may be associated with appearance, changes in cellular distribution of HLA-A,B,C antigens, and/or dissociation in the expression of the two subunits. Analysis of primary tumors and of autologous metastases showed heterogeneity in the expression of HLA-A,B,C antigens among lesions removed from different sites. The degree of heterogeneity did not correlate with the site of origin of metastases.