Percutaneous endovascular Y-stenting of a malignant superior vena cava and innominate vein obstruction.

Superior vena cava syndrome (SVCS) is considered one of the telltale signs of a terminal malignant process. We describe a successful endovascular desobliteration of a subtotal occluded SVC and the left innominate vein using a Y-stent technique in a 46-year-old female with a mediastinal nodal metastasis of a relapsing renal cell carcinoma. Complete clinical improvement in the symptoms within the first 24 hours of the procedure and no complication were observed.

PTSD: diagnosis, evolution, and treatment of combat-related psychological/psychiatric injury.

The long Iraq and Afghanistan conflicts have thrust Combat Related Post-Traumatic Stress Disorder (CR-PTSD) into the public consciousness and promoted national dialogue on the incidence and results of war related psychological trauma. In the first of a two part series we outline our contemporary understanding of CR-PTSD, the evolution of the diagnosis throughout the history of modern warfare, its impact on the mind and body, and its treatment. PTSD has become the mental health issue of our time.

Efficient isolation of novel human monoclonal antibodies with neutralizing activity against HIV-1 from transgenic mice expressing human Ig loci.

Despite considerable interest in the isolation of mAbs with potent neutralization activity against primary HIV-1 isolates, both for identifying useful targets for vaccine development and for the development of therapeutically useful reagents against HIV-1 infection, a relatively limited number of such reagents have been isolated to date. Human mAbs (hu-mAbs) are preferable to rodent mAbs for treatment of humans, but isolation of hu-mAbs from HIV-infected subjects by standard methods of EBV transformation of B cells or phage display of Ig libraries is inefficient and limited by the inability to control or define the original immunogen. An alternative approach for the isolation of hu-mAbs has been provided by the development of transgenic mice that produce fully hu-mAbs.

Platelet-derived growth factor D: tumorigenicity in mice and dysregulated expression in human cancer.

Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes, as well as in human cancer and other proliferative disorders. We have recently isolated and characterized a novel protease-activated member of the PDGF family, PDGF D. PDGF D has been shown to be proliferative for cells of mesenchymal origin, signaling through PDGF receptors.

Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy.

Overexpression of epidermal growth factor receptor (EGFr) has been demonstrated on many human tumors, and the increase in receptor expression levels has been linked with a poor clinical prognosis. Blocking the interaction of EGFr and the growth factors could lead to the arrest of tumor growth and possibly result in tumor cell death. To this end, using XenoMouse technology, ABX-EGF, a human IgG2 monoclonal antibody (mAb) specific to human EGFr, has been generated.

Transgenic mice as a source of fully human antibodies for the treatment of cancer.

The last two years have seen a renaissance of monoclonal antibodies for the treatment of disease. Of the eight antibodies currently approved for human therapy, two are for the treatment of cancer. In large part, the revival of antibodies has been driven by technology developments geared toward making antibodies less likely to elicit an anti-antibody response in humans.

Production of protective human antipneumococcal antibodies by transgenic mice with human immunoglobulin loci.

Infections with Streptococcus pneumoniae remain a significant cause of morbidity and mortality. To gain insight into structure-function relationships for human antibodies to pneumococcal capsular polysaccharide (PPS), we studied the response of transgenic mice reconstituted with human immunoglobulin loci, XenoMouse, to PPS antigens in a pneumococcal vaccine. Enzyme-linked immunosorbent assays of sera from mice vaccinated with a 23-valent pneumococcal vaccine revealed that they produced serotype-specific human antibodies, with the greatest response being to the PPS of serotype 3 (PPS 3).

Fully human anti-interleukin-8 monoclonal antibodies: potential therapeutics for the treatment of inflammatory disease states.

Interleukin-8 (IL-8) is a potent chemotactic cytokine implicated in the pathogenesis of a number of inflammatory disease states. Agents that block the binding of IL-8 to its receptor have been shown to block inflammation in animal models of disease. This suggests that drugs specifically targeting IL-8 may prove efficacious in treating multiple human diseases.

Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy.

A fully human IgG2kappa monoclonal antibody (MAb), E7.6.3, specific to the human epidermal growth factor (EGF) receptor (EGFr) was generated from human antibody-producing XenoMouse strains engineered to be deficient in mouse antibody production and to contain the majority of the human antibody gene repertoire on megabase-sized fragments from the human heavy and kappa light chain loci.

Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer's disease brain.

The deposition of the beta amyloid peptide in neuritic plaques and cerebral blood vessels is a hallmark of Alzheimer's disease (AD) pathology. The major component of the amyloid deposit is a 4.2-kDa polypeptide termed amyloid beta-protein of 39-43 residues, which is derived from processing of a larger amyloid precursor protein (APP).

Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice.

We constructed two megabase-sized YACs containing large contiguous fragments of the human heavy and kappa (kappa) light chain immunoglobulin (Ig) loci in nearly germline configuration, including approximately 66 VH and 32 V kappa genes. We introduced these YACs into Ig-inactivated mice and observed human antibody production which closely resembled that seen in humans in all respects, including gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with somatic hypermutation enables the mice to generate high affinity fully human antibodies to multiple antigens, including human proteins.

Therapy of streptozotocin induced diabetes with a bifunctional antibody that delivers vinca alkaloids to IL-2 receptor positive cells.

IVA039.1 is a bifunctional antibody with specificity for the murine IL-2 receptor and vinca alkaloids. Biodistribution studies show that IVA039.

Reduction of toxicity of a vinca alkaloid by an anti-vinca alkaloid antibody.

Inadvertent oncolytic overdoses occur rarely, but can have serious consequences. We have investigated the possibility of using an antibody, 27.8.

Production and in vivo characterization of a bifunctional antibody (IVA039.1) with specificity for the mouse interleukin-2 receptor and vinca alkaloids.

The autoreactive T cell plays a pivotal role in the pathogenesis of type I diabetes in humans and in rodent animal models. Elimination or attenuation of these cells may provide a means to treat the disease. The use of antibodies directed to T cells has shown varying degrees of effectiveness in the treatment of autoimmune disease.

In vivo antitumor activity of a panel of four monoclonal antibody-vinca alkaloid immunoconjugates which bind to three distinct epitopes of carcinoembryonic antigen.

A panel of four murine monoclonal antibodies apparently directed against three distinct epitopes of carcinoembryonic antigen (CEA) was conjugated via oxidized carbohydrate groups to 4-desacetylvinblastine-3-carboxyhydrazide. The resulting antibody-vinca conjugates were evaluated for antitumor activity against 2-9-day-established LS174T human colorectal carcinoma xenografts. The antibodies (immunoglobulin G, IgG) employed in this study were 11.

Immunoglobulins secreted by a hybrid-hybridoma: analysis of chain assemblies.

In addition to the bispecific antibody, the hybrid-hybridoma 28.19.8 secretes antibodies monospecific for carcinoembryonic antigen (CEA) and antibodies monospecific for vinca alkaloids.

[The usefulness and importance of functional progesterone and estrogen tests in the study of amenorrheas].

One hundred and eighty-two patients who complained of amenorrhea were tested with progesterone and oestrogen. The results are correlated with the diagnosis of the causes. The etiology is related with hypothalamic, hypophysiary, ovarian and/or uterine origins and dysfunction.

Xenogeneic monoclonal antibodies in the management of cancer: control of their in vivo immunogenicity and induction of specific unresponsiveness using an antibody-drug immunoconjugate.

A bispecific mouse monoclonal antibody (mAb) that recognises carcinoembryonic antigen (CEA) with one binding site and vinblastine (VLB) with the other was used, and its in vivo immunosuppressive effect specific for anti-mouse immunoglobulin (Ig) was studied. The antibody was incubated with VLB at a molar ratio (MR) of 1:1, and administered i.v.

Suppression of well-established tumour xenografts by a hybrid-hybrid monoclonal antibody and vinblastine.

The hybrid-hybrid monoclonal antibody 28-19-8 has specificity for the tumour-associated antigen carcinoembryonic antigen and the vinca alkaloids. This bifunctional antibody has been used to target unmodified vinblastine sulphate to well-established MAWI human tumour xenografts implanted in nude mice. The highly significant suppression of tumour growth achieved throughout treatment has also been sustained for over 2 months after the withdrawal of treatment.