Fluorescent Flavin/PVP-Coated Silver Nanoparticles: Design and Biological Performance.

A red-emitting fluorescent Riboflavin (RF)/Polyvinylpyrrolidone (PVP)-coated silver nanoparticles system, λem = 527 nm, Φ = 0.242, with a diameter of the metallic core of 27.33 nm and a zeta potential of - 25.05 mV was prepared and investigated regarding its biological activity. We found that PVP has a key role in RF adsorption around the SNPs surface leading to an enhancement of antioxidant properties (∼70%), low cytotoxicity (> 90% cell viability, at 50 µL/mL, after 48 h of incubation) as well as to an efficient process of its cellular uptake (∼ 60%, after 24 h of incubation) in L929 cells. The results are relevant concerning the involvement of RF and its coenzymes forms in SNPs - based systems, in cellular respiration as well as for future studies as antioxidant marker system on tumoral cells for viewing and monitoring them, by cellular imaging.

Vaccination, life expectancy, and trust: patterns of COVID-19 and measles vaccination rates around the world.

OBJECTIVES: We estimate patterns of covariation between COVID-19 and measles vaccination rates and a set of widely used indicators of human, social, and economic capital across 146 countries. STUDY DESIGN: We conduct exploratory analyses of social patterns that uphold vaccination success for COVID-19 and measles. METHODS: We use publicly available data on COVID vaccination rates and other country-level indicators from Our World in Data, Human Development Report, Corruption Perception Index, and the World Bank to devise bivariate correlations and multiple regression models. RESULTS: About 70% of the variability in COVID-19 vaccination rates in February 2022 can be explained by differences in the Human Development Index (HDI) and, specifically, in life expectancy at birth. Trust in doctors and nurses adds predictive value beyond HDI, clarifying controversial discrepancies between vaccination rates in countries with similar levels of HDI and vaccine availability. Cardiovascular disease deaths, an indicator of general health system effectiveness, and infant measles immunization coverage, an indicator of country-level immunization effectiveness, are also significant, though weaker, predictors of COVID-19 vaccination success. Measles vaccination in 2019 is similarly predicted by HDI and trust in doctors and nurses. CONCLUSIONS: The remaining variability in COVID-19 vaccination success that cannot be pinned down through these sets of metrics points to a considerable scope for collective and individual agency in a time of crisis. The mobilization and coordination in the vaccination campaigns of citizens, medical professionals, scientists, journalists, and politicians, among others, account for at least some of this variability in overcoming vaccine hesitancy and inequity.

Antioxidant and antiproliferative effect of a glycosaminoglycan extract from Rapana venosa marine snail.

Marine glycosaminoglycans (GAG) isolated from different invertebrates, such as molluscs, starfish or jellyfish, have been described as unique molecules with important pharmacological applications. Scarce information is available on GAG extract from Rapana venosa marine snail. The aim of this study was to isolate a GAG extract from R. venosa marine snail and to investigate its physicochemical, antioxidant and antiproliferative properties for further biomedical use. The morphology, chemical and elemental composition of the extract were established as well as the sulfate content and N- to O-sulfation ratio. Fourier transform infrared (FTIR) spectra indicated that GAG extract presented similar structural characteristics to bovine heparan sulfate and chondroitin sulfate. The pattern of extract migration in agarose gel electrophoresis and specific digestion with chondroitinase ABC and heparinase III indicated the presence of a mixture of chondroitin sulfate-type GAG, as main component, and heparan sulfate-type GAG. Free radical scavenging and ferric ion reducing assays showed that GAG extract had high antioxidant activity, which slightly decreased after enzymatic treatment. In vitro MTT and Live/Dead assays showed that GAG extract had the ability to inhibit cell proliferation in human Hep-2 cell cultures, at cytocompatible concentrations in normal NCTC clone L929 fibroblasts. This capacity decreased after enzymatic digestion, in accordance to the antioxidant activity of the products. Tumoral cell migration was also inhibited by GAG extract and its digestion products. Overall, GAG extract from R. venosa marine snail exhibited antioxidant and antiproliferative activities, suggesting its potential use as novel bioactive compound for biomedical applications.

Recurrent left Bockdalek hernia in adult, a rare cause of subocclusive syndrome.

PURPOSE: To present a rare clinical case of a subocclusive syndrome caused by recurrence of a left Bockdalek hernia, with emphasis on the radiological diagnosis and surgical treatment. The current paper presents a 36 year old female with past surgical history of Bockdalek hernia repaired 7 years ago using a diaphragmorrhaphy by thoraco-abdominal approach who presented with a subocclusive syndrome and epigastric pain. Upper endoscopy showed a duodenal ulcer positive for H. pylori. Initial abdominal CT scan was read as negative. On a closer evaluation of the CT images, a small Bockdalek hernia was appreciated, with the elevation of the left colic angle through the diaphragm. Given the occlusive symptoms, the patient underwent surgical treatment with diaphragmorrhaphy and alloplasty with polypropylene mesh, using an open approach. Postoperatively, the patient had a favourable course, being discharged home two days later. To date, there are 173 cases of Bockdalek hernia in the the medical literature, but none with a recurrence. Bockdalek hernia is a rare disease, with non-specific symptoms. It has a broad differential diagnosis that may delay early identification and management. The surgical treatment, either open or laparoscopic, must follow the current recommendations of the surgical societies, including mesh alloplasty to prevent recurrences.

Patterns of protection, infection, and detection: Country-level effectiveness of COVID-19 vaccination in reducing mortality worldwide.

Background: The relationship between COVID-19 vaccination and mortality has been established through clinical trials and other investigations at the individual level. In this study, we aimed to investigate the negative relationship between mortality and COVID-19 vaccination at country level. Study design: We conducted an exploratory, correlational, country-level analysis of open data centralized by Our World in Data concerning the cumulative COVID-19 mortality for the winter wave (October 2021-March 2022) of the pandemic as function of the vaccination rate in October 2021. Methods: We controlled variables that capture country-level social development and level of testing. We also deployed three segmentation tactics, distinguishing among countries based on their level of COVID-19 testing, age structure, and types of vaccines used. Results: Controlling for confounding factors did not highlight a statistically significant relationship between vaccination and cumulative mortality in the total country sample. Still, a strong, significant, negative relationship between cumulative mortality (log scale) and vaccination was highlighted through segmentation analysis for countries positioned at the higher end of the social development spectrum. The strongest estimate for vaccine effectiveness at ecological level was obtained for the set of countries that used Western-only vaccines. Conclusions: COVID-19 testing (log scale) has a significant and positive relationship with cumulative mortality for all subsamples, consistent with patterns of under- and overreporting of COVID-19 deaths at country level, partly driven by testing. This indicates that testing intensity should be controlled as a potential confounder in future ecological analyses of COVID-19 mortality.

Comparative Testing of Two Ligature-Induced Periodontitis Models in Rats: A Clinical, Histological and Biochemical Study.

Experimental animal models for studying the mechanisms of periodontitis and its links are a better alternative to in vitro studies. The aim of this study is to compare two ligature induced periodontitis models and validate the best one for further use in research. An experimental study was performed on male Wistar rats that were divided into three groups: Test 1 (n = 10), incisor ligated, Test 2 (n = 10), molar ligated, and Control (n = 10). The animals were clinically evaluated at the beginning and at the end of the experiment by recording body weight, gingival bleeding index, tooth mobility score, changes in color, and consistency of gingival tissue. Two blood samples were obtained for each animal at baseline and at the end of the experiment. The hematological parameters Interleukin-1 alpha (IL-1 α), high sensitive C Reactive Protein (hsCRP), and Tumor Necrosis Factor-alpha (TNF-α) were measured. Seven days after the induction of periodontitis, the animals were sacrificed, and samples were prepared for histological evaluation. The results of this research demonstrated that the association between clinical, histological, and biochemical parameters initiate a periodontal pathology in the molar induced model in rats while the incisor experimental model initiates only a moderate and incomplete periodontal inflammation, mainly due to mechanical irritation.

First year experience of robotic-assisted laparoscopic surgery with 153 cases in a general surgery department: indications, technique and results.

BACKGROUND: Robotic surgery was developed in response to the limitations and drawbacks of laparoscopic surgery. Since 1997 when the first robotic procedure was performed various papers pointed the advantages of robotic-assisted laparoscopic surgery, this technique is now a reality and it will probably become the surgery of the future. The aim of this paper is to present our preliminary experience with the three-arms "da Vinci S surgical system", to assess the feasibility of this technique in various abdominal and thoracic procedures and to point out the advantages of the robotic approach for each type of procedure. MATERIALS AND METHODS: Between 18 January 2008 and 18 January 2009 153 patients (66 men and 87 women; mean age 48,02 years, range 6 to 84 years) underwent robotic-assisted surgical procedures in our institution; we performed 129 abdominal and 24 thoracic procedures, as follows: one cholecystectomy, 14 myotomies with Dor fundoplication, one gastroenteroanastomosis for unresectable antral gastric cancer, one transthoracic esophagectomy, 14 gastrectomies, one polypectomy through gastrotomy, 22 splenectomies,7 partial spleen resections, 22 thymectomy, 6 Nissen fundoplications, one Toupet fundoplication, one choledocho-duodeno-anastomosis, one drainage for pancreatic abscess, one distal pancreatectomy, one hepatic cyst fenestration, 7 hepatic resections, 29 colonic and rectal resections, 5 adrenalectomies, 12 total radical hysterectomies and pelvic lymphadenectomy, 3 hysterectomies with bilateral adnexectomy for uterine fibroma, one unilateral adnexectomy, and 2 cases of cervico-mediastinal goitre resection. RESULTS: 147 procedures were robotics completed , whereas 6 procedures were converted to open surgery due to the extent of the lesion. Average operating room time was 171 minutes (range 60 to 600 minutes, Median length of stay was 8,6 days (range 2 to 48 days). One system malfunctions was registered. Post-operatory complications occurred in 14 cases. There were no deaths. CONCLUSIONS: Our preliminary experience suggests that robotic surgery is feasible and worth of clinical application. The best indications for robotic surgery are the procedures that require a small operating field, a fine a precise dissection (suitable for pelvic and gastric lymphadenectomy, nerve sparing in total mesorectal excision) and safe intracorporeal sutures.

The robotic-assisted left lateral hepatic segmentectomy: the next step.

INTRODUCTION: During the last decade, minimally invasive surgery had an astonishing development, progressing from minor hepatic interventions to major hepatectomies, thus creating a rich background for robotic-assisted hepatic surgery. Left lateral hepatic segmentectomy (left lobectomy, II-III bi-segmentectomy) is the first anatomic hepatic resection on the learning curve. The purpose of this report is to demonstrate that, due to the anatomical characteristics of the left lobe and to the technical facilities of the robot, this intervention is also feasible with the Da Vinci S robotic system. MATERIALS: In our department, robotic-assisted left lateral lobectomy was performed for both benign and malignant lesions by a surgeon experienced in both hepatic and laparoscopic surgery but traversing the beginning of the learning curve in robotic surgery. A Da Vinci S robotic system with three arms was used and two additional laparoscopic ports for the assistant surgeons were added. RESULTS: The lobectomies were safely performed in an average operatory time of 140 min (+/- 20), with minimal blood loss and without using the Pringle procedure. The dissection was carried out with the bipolar forceps on the left arm of the surgeon and the Harmonic curved shears on the right arm. The division of the vascular pedicles for segments II and III was performed with the LigaSure Atlas device. The other additional port was used for retraction. There were no conversions or reinterventions DISCUSSIONS: Robotic-assisted left lateral hepatic lobectomy was a feasible technique with the potential to reduce surgical trauma and pain and to improve surgeon's technical comfort.

[Laparoscopic left lateral segmentectomy of the liver: indications, technique, results]. / Bisegmentectomia II-III laparoscopica: indicatii, tehnica, rezultate.

INTRODUCTION: The laparoscopic approach of the hepatic lesions located in the left lobe is a frequently used procedure in liver surgery for both benign and malign tumors because of the minimal invasive character, anatomical particularities and modem devices used in hemostasis and biliary-stasis. The purpose of this study is to analyze our experience and report it to the literature data. METHODS AND MATERIAL: The study starts from the basic indications of laparoscopic left lateral segmentectomy, it emphasizes the main operating steps and analyzes the results of this method in a cohort retrospective study in which we included all the laparoscopic resections performed in our center between 1998-2007, both laparoscopic and hand-assisted laparoscopic procedures. We excluded exploratory laparoscopies and the cases in which after the tumor exploration, we decided conversion to open approach in the absence of any intraoperative incidents. RESULTS: Between 1998-2007 we performed 84 laparoscopic hepatic resections out of which 20 were located in the left liver lobe. There were 12 left lateral segmentectomy and in 4 cases we used hand assisted laparoscopy due to bigger tumour dimensions. The hepatic lesions approached laparoscopically were both benign (5 cases out of which 3 hemangioma and 2 adenoma) and malignant (7 cases hepatocellular carcinoma). The tumor diameter ranged between 2-10 cm. The Pringle manoeuvre was never used. CONCLUSIONS: Left lateral segmentectomy can be routinely performed laparoscopically in the absence of any contraindications. This intervention can be accurately performed respecting the limits of oncological security. The results obtained in our center are in accordance with the literature and emphasize the advantages of the minimal invasive approach. On a medium and long term, the results are comparable with those obtained in open surgery.

[The Pringle maneuver in laparoscopic hepatic surgery: is it useful? Analysis of a series of 38 cases]. / Este utila manevra Pringle în chirurgia hepatica prin abord laparoscopic? Analiza unei serii de 38 cazuri.

The Pringle maneuver is the most feasible method to control bleeding in hepatic resections in both open and laparoscopic approach. However its role in the mini-invasive surgery is still questionable. The aim of this study is to analyze our experience and to compare it to the literature data. This is a retrospective cohort study that includes all hepatic laparoscopic resections performed in our department between 1998-2007 and excludes all exploratory laparoscopies and all cases in which conversion to open procedure was imposed after the lesion assessment and in the absence on any intraoperative event. 38 hepatic laparoscopic resections were performed for both benign lesions (20 out of which 13 hemangiomas, 2 focal nodular hyperplasia, 1 liver cell adenoma, 2 hydatic cysts, 2 inflammatory lesions) and malignant lesions (18 out of which 8 metastases, 9 hepatocellular carcinoma, 1 cholangiocarcinoma). The tumor diameter ranged between 2 and 10 cm. There were 2 conversions to open procedures due to bleeding from hepatic veins collaterals. Pringle maneuver was never used. Pringle maneuver did not prove to be useful in our series because, on one hand, we performed only limited laparoscopic hepatic resections and, on the other hand, intraoperative bleeding was mainly due to lesions of the hepatic veins collaterals which cannot be influenced by clamping the hepatic pedicle. Even if there is no consensus, major laparoscopic hepatic resections may benefit from Pringle maneuver.

Indolinone tyrosine kinase inhibitors block Kit activation and growth of small cell lung cancer cells.

Six indolinone tyrosine kinase inhibitors were characterized for their ability to inhibit Kit kinase and for their effects on the growth of small cell lung cancer (SCLC) cell lines. All of the six compounds were potent inhibitors of Kit kinase in a biochemical assay. A homology model of compound binding to the ATP binding site could account for the increased potency observed with the addition of a propionate moiety to the indolinone core but not the increase observed with addition of a chloride moiety. Although all of the compounds tested were potent in the biochemical assay, several exhibited significantly less potency in cellular kinase assays. Their effects on stem cell factor (SCF)-dependent Kit autophosphorylation and SCLC cell growth were also examined. Inhibition of SCF-stimulated Kit activation and cell growth in the H526 cell line was dose-dependent. At concentrations that inhibited SCF-stimulated H526 cell growth, there was little effect on insulin-like growth factor-1-stimulated growth, suggesting that these compounds exhibit reasonable selectivity for inhibition of Kit-mediated proliferation. Higher doses of the compounds were needed to inhibit serum-stimulated growth. Of the six compounds examined, SU5416 and SU6597 demonstrated the best cellular potency and, therefore, their effect on the growth of multiple SCLC cell lines in serum-containing media was examined. In addition to inhibiting proliferation, these compounds also induced significant cell death of several SCLC cell lines, but not of normal human diploid fibroblasts, in complete media. These observations suggest that Kit kinase inhibitors such as these may offer a new approach for inhibiting Kit-mediated proliferation of tumors such as SCLC, gastrointestinal stromal tumors, seminomas, and leukemias.

P235Relation between myocardial deformation by three-dimensional speckle tracking analysis , control of the hypertension and functional capacity in patients with systemic hypertension.

The purpose of this study was to investigate left ventricular (LV) function in hypertensive patients by 3-dimensional (3D) speckle tracking imaging, and determine the relation between the LV mechanics and functional capacity in this population. This cross-sectional study included 20 treated subjects with well-controlled arterial hypertension (group B) and 20 treated participants with uncontrolled hypertension (group A), adjusted by gender and age. All the subjects underwent 24-hour blood pressure monitoring, complete 2-dimensional and 3D examination, and exercise testing. Patients had similar 3D LV ejection fraction. LV mass was higher in group of uncontrolled hypertension (154.71 ± 49.7 g/m2 versus 147.12±44.8 g/m2 p < 0.01), as well as E/E'ratio (11.4 versus 8.9, p =0.02). 3D global longitudinal and circumferential strain and strain rate were significantly decreased in patients with inadequately controlled hypertension (LS 16.25% versus -19.24%, p=0.007, L-SR -0.97/sec versus -1.48/sec, p=0.04, CS -17.89%versus -21.76%, p=0.04, respectively), while the difference of radial strain and strain rate did not reach statistical significance. Group A of patients had also a significantly lower functional capacity (mean duration of test 13,3 min. versus 17,4 min, nr. of METS 9.4 versus 13.7). Duration of exercise was independently associated with LV mass , mean BP at daytime , E/E' ratio and 3D global longitudinal strain (ß = 0.34, p = 0.02) in the whole hypertensive population in our study. In conclusion, LV longitudinal strain and functional capacity are significantly impaired in the patients with uncontrolled hypertension in comparison with the well-controlled hypertensive patients and are independently associated.

The angiogenesis inhibitor SU5416 has long-lasting effects on vascular endothelial growth factor receptor phosphorylation and function.

SU5416, a selective inhibitor of the tyrosine kinase activity of the vascular endothelial growth factor (VEGF) receptor Flk-1/KDR, is currently in Phase III clinical trials for the treatment of advanced malignancies. In cellular assays, SU5416 inhibits the VEGF-dependent mitogenic/proliferative response of human umbilical vein endothelial cells (HUVECs). In tumor xenograft models, SU5416 inhibits the growth of tumors from a variety of origins by inhibiting tumor angiogenesis. In three different human tumor xenograft models, infrequent (once or twice a week) administration of SU5416 is efficacious despite the fact that it has a short plasma half-life (30 min), which suggests that SU5416 has long-lasting inhibitory activity in vivo. The goal of the present study was to determine the basis for the prolonged activity of SU5416. The results indicate that a short (3 h) exposure to 5 microM SU5416 (to mimic plasma levels of the compound as measured in patients who were receiving SU5416 therapy) produced long-lasting (at least 72 h) inhibition of the VEGF-dependent proliferation of HUVECs in culture, which indicate that SU5416 has long-lasting inhibitory activity in vitro as well as in vivo. SU5416 treatment of HUVECs did not affect surface expression of Flk-1/KDR or the affinity of the receptor for VEGF. Instead, the durability of the in vitro activity of SU5416 was shown to be attributable to its long-lasting ability to specifically inhibit VEGF-dependent phosphorylation of Flk-1/KDR and subsequent downstream signaling, although SU5416 is not an irreversible inhibitor of Flk-1/KDR tyrosine kinase activity. The long-lasting inhibition of cellular responses to VEGF was attributable to the accumulation of SU5416 in cells, as shown using radiolabeled compound, such that inhibitory cellular concentrations of SU5416 are maintained long after the removal of the compound from the medium. The long-lasting inhibitory activity of SU5416 in vitro is consistent with the finding that SU5416 has demonstrated evidence of biological activity in clinical studies when administered twice a week despite a short plasma half-life.

Isolation and chemical characterization of the human B29 and mb-1 proteins of the B cell antigen receptor complex.

A disulfide-linked heterodimeric antigen from human B leukemia cells was detected by radioimmunoprecipitation and Western blot analysis using a monoclonal antibody (mAb). The mAb was generated against a cell membrane antigen preparation from human B prolymphocytic leukemia cells and found to define an extracellular epitope of the smaller component (beta chain) of a heterodimeric antigen on human B leukemia cells. The antigen from BALL-1, a human B leukemia cell line, and fresh (uncultured) B prolymphocytic leukemia cells was found to consist of a 44-49 kDa (alpha chain) and a 36-40 kDa (beta chain) component. An additional minor component of 34 kDa was detected in the reduced antigen from BALL-1. For chemical identification of the antigen, we isolated the antigen from a Triton X-100 lysate of BALL-1 by immunoaffinity chromatography using the mAb. Determination of the amino-terminal amino acid sequences of the alpha and beta chains unequivocally identified them as the human mb-1 and B29 proteins, respectively. The sequence analyses indicate the molecular heterogeneity of the mb-1 protein and also perhaps the heterogeneity of the B29 protein. We detected three forms of the mb-1 protein which share an identical amino-terminal amino acid sequence and probably two forms of the B29 protein which share an identical amino-terminal sequence. Our sequence data allowed us to establish the authentic amino-terminal amino acid sequence of the human B29 protein which is different from those proposed by others based on cDNA sequence analyses. Comparison of the amino-terminal sequences of the human mb-1 and B29 proteins with those of the mouse mb-1 and B29 proteins showed that the majority of the conserved amino acids in the mb-1 proteins are hydrophobic amino acids. Such conservation of hydrophobic amino acids is not observed in the amino termini of the human and mouse B29 proteins. A beta-tubulin-like protein was found to be co-purified with the mb-1-B29 antigen in the present study. In addition, we found that there is a strong amino acid sequence homology between the microtubule-binding domains of certain human microtubule-associated proteins and an intracellular segment of the human mb-1 protein.

Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy.

Herein we present the outcome of a high throughput screening (HTS) campaign-based strategy for the rapid identification and optimization of selective and general chemotypes for both kappa (κ) opioid receptor (KOR) activation and inhibition. In this program, we have developed potent antagonists (IC(50) < 120 nM) or agonists of high binding affinity (K(i) < 3 nM). In contrast to many important KOR ligands, the compounds presented here are highly modular, readily synthesized and, in most cases, achiral. The four new chemotypes hold promise for further development into chemical tools for studying the KOR or as potential therapeutic lead candidates.

The minimally invasive approach, laparoscopic and robotic, in rectal resection for cancer. A single center experience.

BACKGROUND: Robotic approach for rectal cancer competes with laparoscopy in centers dedicated to minimally invasive surgery (MIS) due to the technologic advantage. This is a report of our experience with MIS for rectal cancer. METHODS: A series of 84 consecutive patients with laparoscopic resection (between 1995-2010) and 38 consecutive patients with robotic resection (between 2008-2010) for primary rectal cancer were analyzed. Hartmann's procedures were excluded. Clinical and pathologic outcomes were reviewed retrospectively. RESULTS: In the laparoscopic group (LG), 50 anterior rectal resections (ARR), 34 abdominal perineal resections (APR) were performed while in the robotic group(RG) there were 30 ARR and 8 APR. The median operative time was 182 min (140-220 min) in LG and 208 min (180-300 min) in RG (p = 0.0002). No statistically significant difference was noticed between the groups in terms of conversion, morbidity, anastomotic leak and postoperative stay rates. Margin clearance was obtained in all patients and the median number of removed lymph nodes was similar: 11.37 in RG vs. 11.07 in the LG (p = 0.65) with a higher rate of metastatic lymph node involvement in laparoscopy (p = 0.0l012). Blood loss was higher in LG (150 ml vs. 100 ml; p = 0.0001). There were 5 (5.9%) local recurrences in the LG at a median follow-up of 27.5 months and 2 (5.2%) in the RG at a median follow-up of 13 months (p = 0.43). CONCLUSIONS: Minimally invasive surgery for rectal cancer proved to be safe and efficient with similar results in the two groups. Technological advances of robotic approach compared to laparoscopy allowed better ergonomics, more refined dissection, easier preserving of hypogastric nerves and less blood loss. Long term outcomes are to be assessed in prospective randomized studies.

[Use of tissue adhesives in oral surgery]. / L'utilizzo degli adesivi tissutali in chirurgia orale.

The Authors, after a short review of the literature, report their clinical experience using alpha-cyanoacrylate, a new tissue adhesive. This substance shows haemostatic and adhesive properties and it is useful to protect surgical wounds. On these bases, the alpha-cyanoacrylate shows definite directions in oral and maxillo-facial surgery.

Idiotype vaccines against human T cell leukemia. II. Generation and characterization of a monoclonal idiotype cascade (Ab1, Ab2, and Ab3).

Previously, we had generated anti-Id mAb (Ab2) binding to a hybridoma SN2 (Ab1), which recognizes a glycoprotein, gp37, expressed by human leukemic T cells. To characterize these anti-idiotopes further, they were used to immunize mice and rabbits. Several murine anti-anti-Idiotype mAb (Ab3), mostly of IgM-k isotype, were obtained. mAb3 and sera from rabbits immunized with Ab2 contained antibodies that bind to gp37 Ag and leukemic MOLT-4 and JM cells. Also, mAb3 and immune sera from rabbits competed with Ab1 for binding to MOLT-4 cells. They inhibited the binding of iodinated Ab1 to Ab2 indicating that Ab3 in mice and rabbits shares idiotopes with Ab1 (SN2). Furthermore, both the murine mAb3 and rabbit polyclonal Ab3 immunoprecipitated the same gp37 Ag as SN2 (Ab1). The production of Ag-specific Ab3 (Ab1') in mice and rabbits in absence of any exposure to gp37 indicates that these Ab2 may indeed carry the internal image of the gp37 Ag. Such anti-idiotopes (Ab2 beta) may be useful as Ag substitute for the induction of therapeutic immunity in T cell leukemia patients.