Ophthalmic Manifestations in Patients with Blood Malignancies.

Ocular complications can occur in up to 90% of patients with blood malignancies. Such complications range from direct infiltration to local hemostatic imbalance and treatment-related toxicity. This narrative review is based on a systematic computerized search of the literature conducted until January 2024 and examines the common ocular complications associated with blood cancers.

Echocardiographic Evolution of PosteroLateral Left Ventricular Aneurysm with Normal Coronary Arteries in Patient Recently COVID-19 Vaccinated: A Complicated Atypical Case of Takotsubo Syndrome Vaccine-related?

A 72-year-old woman, recently COVID-19 vaccinated with a third dose, was referred to our center for acute chest pain and dyspnea. On admission, the electrocardiography showed a STEMI on inferior derivations and the dyskinesia of the inferior wall was found at the first transthoracic echocardiogram. The coronary angiography did not show coronary artery disease.

Distraction techniques for face and smile aesthetic preventing ageing decay.

Modern concepts in the world of beauty arise from popular models, beautiful faces of actors document a bi-protrusive asset with high tension for soft tissues. Facial symmetry has been proposed as a marker of development and stability that may be important in human mate choice. For various traits any deviation from perfect symmetry can be considered a reflection of imperfect development.

Management of Zygomatic Fractures in Young Patients: Technical Modifications for Aesthetic and Functional Results.

Introduction: The zygomaticomaxillary complex is very vulnerable to injury because of its intrinsically prominent convexity. There are 2 different surgical approaches for the therapy of these fractures: closed reduction and open reduction. In the open reduction 2 or 3 fixation points with related incisions are usually necessary in dislocated fractures: osteosynthesis must be performed starting from zygomaticofrontal suture when dislocated at this site, followed by zygomatic body fixation on the anterior sinus wall, anterior orbital floor margin fixation, and finally orbital floor reconstruction in case of eye globe dislocation with diplopia.

New Techniques in Relation to New Concepts of the Aesthetic of the Face: Technical Considerations and Aesthetic Evaluation.

Aesthetic of the face is greatly changed in relation to common standards of the past. Modern concepts of beauty from popular models of beautiful faces to actors show a biprotrusive asset with high tension for soft tissues. Facial symmetry has been proposed as a marker of developmental stability that may be important in human mate choice.

Hemangiomas of the maxillofacial area: Case Report, Classification and Treatment Planning.

Vascular lesions of the maxillofacial area are even more challenging than in other different body district, because of the high aesthetic and functional relevance of this area for the sense organs presence like eye, brain, tongue, ear and nose. For these reasons, we propose an accurate classification based on hemodynamic and histologic aspects usefulthat is for diagnostic and therapeutic planning. A female, 60 years old patient came to our observation showing a vascular lesion of the lower left lip, and complaining for aesthetical and functional impairment.

Three-dimensional domain swapping and supramolecular protein assembly: insights from the X-ray structure of a dimeric swapped variant of human pancreatic RNase.

The deletion of five residues in the loop connecting the N-terminal helix to the core of monomeric human pancreatic ribonuclease leads to the formation of an enzymatically active domain-swapped dimer (desHP). The crystal structure of desHP reveals the generation of an intriguing fibril-like aggregate of desHP molecules that extends along the c crystallographic axis. Dimers are formed by three-dimensional domain swapping.

Ribonuclease/angiogenin inhibitor 1 regulates stress-induced subcellular localization of angiogenin to control growth and survival.

Angiogenin (ANG) promotes cell growth and survival. Under growth conditions, ANG undergoes nuclear translocation and accumulates in the nucleolus where it stimulates rRNA transcription. When cells are stressed, ANG mediates the production of tRNA-derived stress-induced small RNA (tiRNA), which reprograms protein translation into a survival mechanism.

A novel interdomain interface in crystallins: structural characterization of the βγ-crystallin from Geodia cydonium at 0.99 Å resolution.

The βγ-crystallin superfamily includes highly diverse proteins belonging to all of the kingdoms of life. Based on structural topology, these proteins are considered to be evolutionarily related to the long-lived βγ-crystallins that constitute the vertebrate eye lens. This study reports the crystallographic structure at 0.

Mechanisms of cardiotoxicity associated with ErbB2 inhibitors.

The ErbB2 receptor is a proto-oncogene associated with a poor prognosis in breast cancer. Herceptin, the only humanized anti-ErbB2 antibody currently in clinical use, has proven to be an essential tool in the immunotherapy of breast carcinoma, but induces cardiotoxicity. ErbB2 is involved in the growth and survival pathway of adult cardiomyocytes; however, its levels in the adult heart are much lower than those found in breast cancer cells, the intended targets of anti-ErbB2 antibodies.

Effects of a human compact anti-ErbB2 antibody on prostate cancer.

Prostate cancer is the most commonly diagnosed malignancy in men in developed countries. ErbB2, a tyrosine kinase receptor overexpressed in many human cancer types, contributes to prostate cancer progression by activating the androgen receptor in a steroid poor environment, thus promoting androgen-independent cell growth. The consequent development of hormone refractory tumors is a major obstacle in prostate cancer therapy.

Comparison of preclinical cardiotoxic effects of different ErbB2 inhibitors.

Two novel human antitumor immunoconjugates, made up of a human anti-ErbB2 scFv, Erbicin, fused with either a human RNase or the Fc region of a human IgG1, are selectively cytotoxic for ErbB2-positive cancer cells in vitro and in vivo. The Erbicin-derived immunoagents (EDIA) target an epitope different from that of trastuzumab, the only humanized antibody currently prescribed for treatment of ErbB2-positive breast cancer (BC). As Trastuzumab has shown cardiotoxic effects, in this study, we evaluated if any side effects were exerted also by EDIA, used as single agents or in combination with anthracyclines.

Denatured bactericidal proteins: active per se, or reservoirs of active peptides?

According to the structure-to-function paradigm proteins fold into a 3D structure for exerting their functions. Intrinsically destructured proteins with important biological functions have been identified and studied, but they assume a structure when interacting in the cell with their partners. There are instead bactericidal proteins, endowed also with other diverse activities (glycoside hydrolases, RNases, a defensin), which are lost when the proteins are denatured or inactivated, whereas the bactericidal activity is surprisingly conserved.

A novel ErbB2 epitope targeted by human antitumor immunoagents.

Two novel human antitumor immunoconjugates, engineered by fusion of a single-chain antibody fragment against human ErbB2 receptor, termed Erbicin, with either a human RNase or the Fc region of a human IgG(1) , are selectively cytotoxic for ErbB2-positive cancer cells in vitro and in vivo. These Erbicin-derived immunoagents (EDIAs) do not show the most negative properties of Herceptin, the only humanized mAb against ErbB2 used in the therapy of breast carcinoma: cardiotoxicity and the inability to act on resistant tumors. These differences are probably attributable to the different ErbB2 epitopes recognized by EDIAs and Herceptin, respectively, as we have previously reported that they induce different signaling mechanisms that control tumor and cardiac cell viability.

The ribonuclease/angiogenin inhibitor is also present in mitochondria and nuclei.

The data presented here show for the first time that the protein known as "ribonuclease (RNase) inhibitor" (RI or RNH1) is present not only in the cell cytosol, but also in mitochondria, the central organelles in cell redox homeostasis. This finding directly correlates with the reported ability of RI to protect the cell from oxidative stress, with its sensitivity to oxidation and reactivity as a reactive oxygen species scavenger. While this study was carried out we also surprisingly discovered the presence of RI in the cell nucleus.

Structure-cytotoxicity relationships in bovine seminal ribonuclease: new insights from heat and chemical denaturation studies on variants.

Bovine seminal ribonuclease (BS-RNase), a homodimeric protein displaying selective cytotoxicity towards tumor cells, is isolated as a mixture of two isoforms, a dimeric form in which the chains swap their N-termini, and an unswapped dimer. In the cytosolic reducing environment, the dimeric form in which the chains swap their N-termini is converted into a noncovalent dimer (termed NCD), in which the monomers remain intertwined through their N-terminal ends. The quaternary structure renders the reduced protein resistant to the ribonuclease inhibitor, a protein that binds most ribonucleases with very high affinity.

A new RNase sheds light on the RNase/angiogenin subfamily from zebrafish.

Recently, extracellular RNases of the RNase A superfamily, with the characteristic CKxxNTF sequence signature, have been identified in fish. This has led to the recognition that these RNases are present in the whole vertebrate subphylum. In fact, they comprise the only enzyme family unique to vertebrates.

IL-6 Induction by TNFα and IL-1β in an Osteoblast-Like Cell Line.

Stress cytokines tumor necrosis factor α, interleukin-1 β and interleukin-6 modulate the activity of a variety of cell types including osteoblasts, and are involved in the pathogenesis of several rheumatic diseases associated with systemic bone loss. We have studied the expression of interleukin-6 induced by interleukin-1 β and tumor necrosis factor α in the osteoblast-like cell line MG-63, derived from a human osteosarcoma. We have observed marked differences in the regulation of interleukin-6 gene expression by tumor necrosis factor α or interleukin-1 β, at the level of mRNA steady state and stability and cytokine secretion.

Characterization of the angiogenic activity of zebrafish ribonucleases.

Ribonucleases identified from zebrafish possess angiogenic and bactericidal activities. Zebrafish RNases have three intramolecular disulfide bonds, a characteristic structural feature of angiogenin, different from the typical four disulfide bonds of the other members of the RNase A superfamily. They also have a higher degree of sequence homology to angiogenin than to RNase A.

Cardiotoxic effects, or lack thereof, of anti-ErbB2 immunoagents.

This study investigated potential cardiotoxicity as exerted by Erbicin-derived-immunoagents (EDIAs), novel human anti-ErbB2 immunoagents engineered by fusion of a human anti-ErbB2 scFv, Erbicin, with either a human RNase or the Fc region of a human IgG1. EDIAs are strongly cytotoxic on ErbB2-positive cells in vitro and in vivo and bind to an epitope different from that of Herceptin, a humanized anti-ErbB2 mAb effective in the therapy of breast carcinoma, but cardiotoxic in a high percentage of cases. Toxicity and apoptosis were tested in vitro by 3-(4,5-dimethyl-2-thizolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), DNA fragmentation, and immunoblotting analyses.

Human anti-ErbB2 immunoagents--immunoRNases and compact antibodies.

Immunotherapy, based on mAbs specifically directed against cancer cells, is considered a precious strategy in the fight against cancer because of its selectivity and lack of multidrug resistant effects. However, there are obstacles to the complete success of current immunotherapy such as immune responses to nonhuman or even humanized antibodies and the large size of the antibodies, which hinders their diffusion into bulky tumors. Fully human, small immunoagents, capable of inhibiting tumor growth may overcome these problems and provide safe, highly selective and effective antitumor drugs.

It takes two to flirt with a dimeric RNase.

In my long RNase-life-time I have had the fortune to entertain with Lelio Mazzarella what I have called special interactions, which not only advanced my knowledge of proteins but also gave pleasure, as one obtains by reading a beautiful book, an inspiring poem, or watching a very good movie. In this article, I recall the more than 30-year long story of these interactions in which "it took two," a structural biologist with his coworkers and a biochemist with his coworkers, to flirt with an unusual, dimeric RNase.

Temporal and spatial expression of RNases from zebrafish (Danio rerio).

We have recently isolated and characterized three zebrafish (Danio rerio) RNases, ZF-RNase-1,-2 and -3, endowed with diverse bioactivities, including microbicidal and angiogenic activities. In the present study we have analyzed their temporal and spatial gene expression profiles. Our results indicate that the three ZF-RNase genes have a differential expression pattern, with ZF-RNase-1 having the most unique and dynamic expression profile.

Differential binding of human immunoagents and Herceptin to the ErbB2 receptor.

Overexpression of the ErbB2 receptor is associated with the progression of breast cancer, and is a sign of a poor prognosis. Herceptin, a humanized antibody directed to the ErbB2 receptor, has been proven to be effective in the immunotherapy of breast cancer. However, it can result in cardiotoxicity, and a large fraction of breast cancer patients are resistant to Herceptin treatment.