Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment.

Background: Association of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D) has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment ameliorated diabetes in rats and similar improvements have been seen in human patients. Treatment of amyloid precursor protein (APP) transgenic mice with Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42 protein levels in the brain tissues of the mice.

Body weight reduction in rats by oral treatment with zinc plus cyclo-(His-Pro).

Background And Purpose: We have previously shown that treatment with zinc plus cyclo-(His-Pro) (CHP) significantly stimulated synthesis of the insulin degrading enzyme and lowered plasma insulin and blood glucose levels, alongside improving oral glucose tolerance in genetically type 2 diabetic Goto-Kakizaki (G-K) rats and in aged obese Sprague-Dawley (S-D) rats. Thus, we postulated that zinc plus CHP (ZC) treatment might also improve body weight control in these rats. We therefore determined the effects of ZC treatment on body weights in both genetically diabetic, mature G-K rats and non-diabetic, obese S-D rats.

Host resistance and immune responses in advanced age.

Immunosenescence results in populating immune tissues with less functional T cells, and perhaps B cells dendritic cells, that do not function well and produce more type 2 cytokines and fewer type 1 cytokines. Impaired immunity, distinct from immunosenescence, correlates more with disease burden than chronologic age. Older adults who have chronic diseases or chronic infections are more susceptible to common infections and have poor vaccine responses.

Lhx2 mediates the activity of Six3 in zebrafish forebrain growth.

The telencephalon shows the greatest degree of size variation in the vertebrate brain. Understanding the genetic cascade that regulates telencephalon growth is crucial to our understanding of how evolution of the normal human brain has supported such a variation in size. Here, we present a simple and quick approach to analyze this cascade that combines caged-mRNA technology and the use of antisense morpholino oligonucleotides in zebrafish embryos.

Comorbidity is a better predictor of impaired immunity than chronological age in older adults.

Objectives: To determine whether high level of comorbidity, measured using a standardized instrument, can predict impaired immunity in older adults.

Setting: Geriatric outpatient Clinic and Nursing Home Care Unit of Veterans Affairs Greater Los Angeles Healthcare System.

Participants: Fifteen men aged 51 to 95 with varying levels of chronic illness.

Zebrafish gcmb is required for pharyngeal cartilage formation.

The glial cells missing (gcm) gene in Drosophila encodes a GCM-motif transcription factor that functions as a binary switch to select between glial and neuronal cell fates. To understand the function of gcm in vertebrates, we isolated the zebrafish gcmb and analyzed the function of this gene using antisense morpholino oligonucleotides against gcmb mRNA (gcmb-MO) and transgenic overexpression. Zebrafish gcmb is expressed in the pharyngeal arch epithelium and in cells of the macrophage lineage.

Neural cell adhesion molecule L1 is required for fasciculation and routing of thalamocortical fibres and corticothalamic fibres.

To examine the role of neural cell adhesion molecule L1 in thalamocortical projections, we analysed L1 deficient (L1-/y) mice. Immunohistochemistry of pleiotrophin/HB-GAM, a marker for thalamocortical axons and axonal tracing experiments showed that thalamocortical axons were abnormally and highly fasciculated when they pass through the developing internal capsule. Within the cortex, however, their course was more diffuse.

Immune dysfunction in the elderly and its reversal by antihistamines.

The decline in immunity seen in the elderly is a significant contributor to disease burden. This decline has largely been attributed to alterations in T cell immunity and contributes to an overall increased risk and severity of infection in the elderly. A key component of T cell immunity involves antigen presentation, an event where an antigen is processed and presented to specific immune cells for destruction.

Towards crystallization of hydrophobic myelin glycoproteins: P0 and PASII/PMP22.

The preparation of a pure and homogeneous protein sample at proper concentration is a prerequisite for success when attempting their crystallization for structural determination. The detergents suitable for solubilization particularly of membrane proteins are not always the best for crystallization. Myelin of the peripheral nervous system of vertebrates is the example of a membrane for which neutral or "gentle" detergents are not even strong enough to solubilize its proteins.

The frail elderly: role of dendritic cells in the susceptibility of infection.

The decline in immunity in the elderly has largely been attributed to impairment of T cell mechanisms. This seems reasonable since the thymus involutes with age, so that the number of naïve cells to respond to new foreign antigens also declines. However, little is known about how aging affects antigen-presenting cells (APC) that are responsible for the initiation and outcome of effector T cell immune responses.

Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms.

Herpes vector has been widely used for experimental gene therapy. We herein review the strategies of such therapy for the treatment of urologic neoplasms. Most experimental studies of genetically altered viruses have employed replication-incompetent vectors.

Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV.

Here we developed an effective therapeutic approach using a replication-conditional mutant of herpes simplex virus (HSV), G207, for the treatment of metastatic tumors in the immunologically privileged central nervous system. An experimental model of brain metastasis was developed using BALB/c mice that harbored both intracranial (i.c.

The roles of cell adhesion molecules on the formation of peripheral myelin.

Several cell adhesion molecules of the immunoglobulin superfamily (IGSF) are expressed differently during the development and myelination of the peripheral nervous system. To examine the relationship between the expression of IGSF molecules and Schwann cell differentiation, we established a useful system for myelin formation in vitro on collagen gel using primary neuron/Schwann cell co-cultures from neonatal dorsal root ganglions (DRG). At 10 days in vitro (DIV), many Schwann cells were found in the areas surrounding aggregates of DRG neurons.

Increase of oligodendrocyte progenitor cells after spinal cord injury.

The reaction of oligodendrocyte progenitor cells (OPCs) after spinal cord injury (SCI) is poorly understood. In this study, we examined oligodendroglial reactions after contusion SCI in adult rats by immunohistochemistry. OPCs were identified by staining with monoclonal antibodies (mAbs) A2B5 and O4.

Functional analysis for peripheral myelin protein PASII/PMP22: is it a member of claudin superfamily?

Two major glycoproteins, P0 and PASII/PMP22, are specifically expressed in peripheral myelin. Point mutations of these proteins and over or under expression of PASII/PMP22 cause various hereditary peripheral neuropathies. P0 is well characterized as a major adhesion molecule in PNS myelin, but the function of PASII/PMP22 is still unknown.

A role for IL-12 receptor expression and signal transduction in host defense in leprosy.

The generation of cell-mediated immunity against intracellular infection involves the production of IL-12, a critical cytokine required for the development of Th1 responses. The biologic activities of IL-12 are mediated through a specific, high affinity IL-12R composed of an IL-12Rbeta1/IL-12Rbeta2 heterodimer, with the IL-12Rbeta2 chain involved in signaling via Stat4. We investigated IL-12R expression and function in human infectious disease, using the clinical/immunologic spectrum of leprosy as a model.

Functional repression of Islet-2 by disruption of complex with Ldb impairs peripheral axonal outgrowth in embryonic zebrafish.

Islet-2 is a LIM/homeodomain-type transcription factor of the Islet-1 family expressed in embryonic zebrafish. Two Islet-2 molecules bind to the LIM domain binding protein (Ldb) dimers. Overexpression of the LIM domains of Islet-2 or the LIM-interacting domain of Ldb proteins prevented binding of Islet-2 to Ldb proteins in vitro and caused similar in vivo defects in positioning, peripheral axonal outgrowth, and neurotransmitter expression by the Islet-2-positive primary sensory and motor neurons as the defects induced by injection of Islet-2-specific antisense morpholino oligonucleotide.

Expression of the neural RNA-binding protein Musashi1 in human gliomas.

Tumor cells arising from a particular tissue may exhibit the same gene expression patterns as their precursor cells. To test this proposition, we have analyzed the expression of a neural RNA-binding protein, Musashi1, in primary human central nervous system (CNS) tumors. In rodents, Musashi1 is expressed predominantly in proliferating multipotent neural precursor cells, but not in newly generated postmitotic neurons.

Treatment of human renal cell carcinoma by a conditionally replicating herpes vector G207.

Purpose: Surgical removal remains the only potentially curative therapy for renal cell carcinoma. In this study we evaluated the inhibitory effect of the replication competent engineered herpes simplex virus type 1, G207, for renal cell carcinoma in vitro and in vivo.

Materials And Methods: The nature of G207 enables it to replicate within cancer cells, thus, causing cytolysis, but replication is restricted within normal cells.

Expression of peripheral myelin protein zero in sural nerve of patients with Charcot-Marie-Tooth disease 1B.

A Charcot-Marie-Tooth disease 1B (CMT1B) family with a mutation of the Po gene is presented. A to G substitution of nucleotide 389 in exon 3 resulted in Lys 131 Arg substitution. Immunostaining for Po in biopsied sural nerve from one family member with CMT1B was expressed in a small number of myelinated fibers.

Conservation of K1 immunoreactivity against early cortical neurones in the vertebrate telencephalon.

A monoclonal antibody, K1, immunostains neurones generated earliest in the rat neocortex. The K1 immunoreactivity was found in both mouse and human embryos. In the human marginal zone, the subpial granular layer and the inner sublayer were stained at the 19th and 20th week of gestation, respectively.

A novel monoclonal antibody K1 recognises early neurones in the rat cortex.

The aim of this study was to produce monoclonal antibodies specific for neurones that are generated earliest in the rat neocortex. One of the established clones, K1, showed a strong immunoreactivity in the marginal zone at the 19th day of gestation (E19). The immunoreactivity of K1 initially appeared in the primordial plexiform layer at E15, in the subplate at E16, and in the marginal zone by E17.

Oncolytic viral therapy for human prostate cancer by conditionally replicating herpes simplex virus 1 vector G207.

Over the last few years, a conditionally replicating herpes simplex virus 1 (HSV-1) vector, G207 has been used for the treatment of several malignant tumors. In this article we evaluate the anti-tumoral effect of G207 against prostate cancer in vitro and in vivo. The susceptibility of the human prostate cancer cell lines, DU145 and PC3 to G207 at a multiplicity of infection (MOI) of 0.