Intravenously-injected gold nanoparticles (AuNPs) access intracerebral F98 rat gliomas better than AuNPs infused directly into the tumor site by convection enhanced delivery.

Background: Intravenously (IV)-injected gold nanoparticles (AuNPs) powerfully enhance the efficacy of X-ray therapy of tumors including advanced gliomas. However, pharmacokinetic issues, such as slow tissue clearance and skin discoloration, may impede clinical translation. The direct infusion of AuNPs into the tumor might be an alternative mode of delivery.

Biodistribution of gold nanoparticles in BBN-induced muscle-invasive bladder cancer in mice.

Bladder-sparing options are being developed for muscle-invasive bladder cancer in place of radical cystectomy, including the combination of chemotherapy and radiation therapy. We reasoned that improving the radiotherapy component of chemoradiation could improve the control of locally advanced disease. Previously, we showed that gold nanoparticles (AuNPs) are potent enhancers of radiation therapy.

Increasing radiation dose improves immunotherapy outcome and prolongation of tumor dormancy in a subgroup of mice treated for advanced intracerebral melanoma.

Previously, we developed a clinically relevant therapy model for advanced intracerebral B16 melanomas in syngeneic mice combining radiation and immunotherapies. Here, 7 days after B16-F10-luc2 melanoma cells were implanted intracerebrally (D7), syngeneic mice with bioluminescent tumors that had formed (1E10(5) to 7E10(6) photons per minute (>1E10(6), large; <1E10(6), small) were segregated into large-/small-balanced subgroups. Then, mice received either radiation therapy alone (RT) or radiation therapy plus immunotherapy (RT plus IT) (single injection of mAbPC61 to deplete regulatory T cells followed by multiple injections of irradiated granulocyte macrophage colony stimulating factor transfected B16-F10 cells) (RT plus IT).

Psychiatrists' use of electronic communication and social media and a proposed framework for future guidelines.

Background: Recent and ongoing advances in information technology present opportunities and challenges in the practice of medicine. Among all medical subspecialties, psychiatry is uniquely suited to help guide the medical profession's response to the ethical, legal, and therapeutic challenges--especially with respect to boundaries--posed by the rapid proliferation of social media in medicine. Ironically, while limited guidelines exist for other branches of medicine, guidelines for the responsible use of social media and information technology in psychiatry are lacking.

Therapy model for advanced intracerebral B16 mouse melanoma using radiation therapy combined with immunotherapy.

A reproducible therapy model for advanced intracerebral B16 melanoma is reported. Implanted tumors (D0), suppressed by a single 15 Gy radiosurgical dose of 100 kVp X-rays (D8), were further suppressed by a single ip injection of a Treg-depleting mAb given 2 days prior to the initiation (D9) of four weekly then eight bi-monthly sc injections of GMCSF-transfected, mitotically disabled B16 cells. The trends of seven independent experiments were similar to the combined result: The median (days) [SD/total N] of survival went from 15[1.

Successful treatment of metastatic retinoblastoma with high-dose chemotherapy and autologous stem cell rescue in South America.

High-dose chemotherapy (HDC) followed by autologous stem cell rescue (ASCR) is the only curative treatment for metastatic retinoblastoma, but its feasibility in developing countries is unknown. We report 11 consecutive children (six unilateral) treated in three South-American middle-income countries with HDC-ASCR. One patient had metastatic retinoblastoma at diagnosis and the remaining ones had a metastatic relapse.

Estrogen replacement raises rat CRP without evidence of complement activation.

Given current controversies regarding anti- and pro-inflammatory effects of estrogen, there is a need to explore relationships between gonadal hormones and inflammation using appropriate animal models. It has been proposed that rats are not appropriate for such research since, contrary to the effect of estrogen in humans, earlier animal studies had reported that estrogen downregulates serum C-reactive protein (rCRP) levels in the rat. With these considerations in mind, we re-examined the effects of estrogen withdrawal and replacement on CRP expression and complement activation in the rat.

Early detection of oleic acid-induced lung injury in rats using (111)In-labeled anti-rat intercellular adhesion molecule-1.

Unlabelled: Previous study of the bleomycin-induced lung injury model suggested that (111)In-labeled antirat intercellular adhesion molecule-1 (aICAM-1) might be a useful acute respiratory distress syndrome (ARDS) diagnostic agent. We further investigated the ability of (111)In-aICAM-1 to detect inflammation in another ARDS lung injury model.

Methods: (111)In-labeled rat polymorphonuclear leukocytes (PMNs), (111)In-aICAM-1, (111)In-labeled normal mouse IgG (nmIgG), and (111)In-labeled rat serum albumin (RSA) were injected into rats 18-24 h before kill.

Novel animal models of affective disorders.

Is there an appropriate animal model for human affective disorders? The traditional difficulties in accepting animal models for psychopathology stem from the argument that there is no evidence for concluding that what occurs in the brain of the animal is equivalent to what occurs in the brain of a human. However, if one models any or some core aspects of affective disorder, this model can become an invaluable tool in the analysis of the multitude of causes, genetic, environmental, or pharmacological, that can bring about symptoms homologous to those of patients with affective disorders. Animal models can also allow the study of the mechanisms of specific behaviors, their pathophysiology, and can aid in developing and predicting therapeutic responses to pharmacologic agents.

Dietary arginine alters time of symptom onset in Huntington's disease transgenic mice.

Recent neuroimaging studies reported complex changes in cerebral blood flow (CBF) in early-staged Huntington's disease (HD) patients. Deckel and co-workers [Deckel and Duffy, Brain Res. (in press); Deckel and Cohen, Prog.

Involvement of matrix metalloproteinases in human immunodeficiency virus type 1-induced replication by clinical Mycobacterium avium isolates.

The role of Mycobacterium avium isolates in modulating human immunodeficiency virus type 1 (HIV-1) replication was examined by use of an in vitro, resting T cell system. Two human clinical isolates (serotypes 1 and 4) but not an environmental M. avium isolate (serotype 2) enhanced HIV-1 replication.

Down-regulation of interleukin-10 expression and production is associated with spontaneous proliferation by lymphocytes from human T lymphotropic virus type II-infected persons.

Cytokines from peripheral blood mononuclear cells (PBMC) from human T lymphotropic virus (HTLV)-II-infected persons were studied to delineate the mechanism(s) of spontaneous lymphocyte proliferation (SLP). Culturing HTLV-II-infected PBMC that spontaneously proliferate (SLP+) resulted in greater mRNA expression and production of interferon-gamma, interleukin (IL)-4, and IL-5, with a concomitant decrease in IL-10, than was seen with nonproliferating (SLP ) and normal PBMC. While IL-2 mRNA expression was higher, production was lower in SLP+ PBMC than in SLP and normal PBMC, implying that the proliferating cells are utilizing IL-2.

Early detection of bleomycin-induced lung injury in rat using indium-111-labeled antibody directed against intercellular adhesion molecule-1.

Unlabelled: We have investigated whether an (111)In-labeled mouse monoclonal antibody to rat intercellular adhesion molecule-1 ((111)In*aICAM-1) could detect lung injury early in rats treated with bleomycin.

Methods: Rats received an intravenous injection of either (111)In*aICAM-1 or (111)In-labeled normal mouse IgG ((111)In*nmIgG) and were imaged and killed 24 hr later. Lung injury was induced by an intratracheal injection of bleomycin 4 or 24 hr before the rats were killed.

[3H]Rauwolscine: an antagonist radioligand for the cloned human 5-hydroxytryptamine2b (5-HT2B) receptor.

In previous reports, [3H]5-HT has been used to characterize the pharmacology of the rat and human 5-HT2B receptors. 5-HT, the native agonist for the 5-HT2B receptor, has a limitation in its usefulness as a radioligand since it is difficult to study the agonist low-affinity state of a G protein-coupled receptor using an agonist radioligand. When using [3H]5-HT as a radioligand, rauwolscine was determined to have relatively high affinity for the human receptor (Ki human = 14.

Biodistribution of indium-111-labeled antibody directed against intercellular adhesion molecule-1.

Unlabelled: We examined the biodistribution in normal rats of an 111In-labeled mouse monoclonal antibody to rat intercellular adhesion molecule-1 (111In-alCAM-1), as a potential detector of inflammation.

Methods: Indium-111-alCAM-1 or 111In-labeled normal mouse polyclonal immunoglobulin G (111In-nmIgG) was injected into rats. Groups of three to four rats were killed up to 18 hr after injection, and activity was measured in various tissues.

Humans with OKT4-epitope deficiency have a single nucleotide base change in the CD4 gene, resulting in substitution of TRP240 for ARG240.

The OKT4 epitope of the CD4 cell-surface protein has been shown to be polymorphic in white, black, and Japanese populations. The variable phenotypic expression is due to an alteration of the OKT4 epitope, since those persons lacking reactivity with OKT4 monoclonal antibody (mAb) are reactive with OKT4A-F mAb as well as other mAb specific for CD4. To determine the nature of this polymorphism at the gene level, we sequenced polymerase chain reaction-amplified genomic DNA containing the CD4-V3 and -V4 exons from American black subjects who are OKT4-normal, OKT4-negative heterozygous, or OKT4-negative homozygous.

Hematologic dysfunction in Lassa fever.

Lassa fever is widespread in West Africa, where the case fatality is about 16% in hospitalized adult patients. The clinical course is highly variable, with a few patients developing severe disease with bleeding, adult respiratory distress syndrome, encephalopathy and hypovolemic shock. We studied 70 patients admitted with suspected Lassa fever to a hospital in Sierra Leone, West Africa.

Construction of a recombinant vaccinia virus expressing the Lassa virus glycoprotein gene and protection of guinea pigs from a lethal Lassa virus infection.

A cloned cDNA (1.65 kb) containing the complete glycoprotein gene of the Josiah strain of Lassa virus was inserted into the thymidine kinase (TK) gene of the New York Board of Health (WYETH) strain of vaccinia virus. The Lassa virus glycoprotein precursor, GPC, and the posttranslational cleavage products, G1 and G2, were shown by Western blot analysis to be properly expressed in cells infected with the recombinant virus.

Physiological and immunologic disturbances associated with shock in a primate model of Lassa fever.

The degree of cell and organ damage in clinical and histological studies of patients dying of Lassa fever has been insufficient to explain the catastrophic shock characteristic of the fatal illness. To explore this issue further, we conducted a study of the evolution of shock in three Lassa virus-infected rhesus monkeys. By the sixth day after infection, a marked, progressive reduction of in vitro platelet aggregation occurred despite normal numbers of circulating platelets and a normal platelet survival time and was accompanied by loss of prostacyclin production by postmortem endothelium.

Nucleotide sequence of the glycoprotein gene and intergenic region of the Lassa virus S genome RNA.

Two overlapping cDNA clones corresponding to the 5' region of the Lassa virus S genome RNA were isolated and their nucleotide sequences determined. Similar to Pichinde and lymphocytic choriomeningitis viruses (LCMV), Lassa virus has an ambisense S RNA. The precursor to the viral glycoproteins (GPC) is encoded in viral RNA sequence originating at position 56 and terminating at position 1529 from the 5' terminus of the S RNA.

Serological and virological evidence of a Hantaan virus-related enzootic in the United States.

The first isolation of a Hantaan-related virus from a feral rat in the United States was made from a Rattus norvegicus caught in New Orleans. The strain, designated Tchoupitoulas virus, is antigenically related to, but distinct from, the prototype strain 76-118 of Hantaan virus and is the first Hantaan-like virus isolated from the pancreas of a naturally infected animal. Serosurveys of wild rodents from urban and rural areas in the United States indicated that Hantaan-related viruses infected urban rats in coastal and inland cities and infected five species of New World rodents in the western United States (Peromyscus maniculatus, Peromyscus difficilis, Peromyscus californicus, Neotoma mexicana, and Neotoma cinerea).

Distinction between Bunyaviridae genera by surface structure and comparison with Hantaan virus using negative stain electron microscopy.

Ultrastructural studies of glutaraldehyde-fixed viruses of the Bunyaviridae were performed by negative-stain electron microscopy. The surface structure of viruses of each genus was compared with that of the other genera and with Hantaan virus, the prototype of a proposed new genus of Bunyaviridae. Viruses of each genus had a surface structure distinct for that genus.

Morphological identification of the agent of Korean haemorrhagic fever (Hantaan virus)as a member of the Bunyaviridae.

Korean haemorrhagic fever (KHF) (Hantaan virus), a rodent-borne viral illness, is an important cause of human disease throughout much of Asia and Eastern Europe. The agent responsible for KHF has not yet been conclusively identified. Plaque-purified KHF virus was concentrated and then banded in a potassium tartrate gradient.