A novel mutation of the arginine vasopressin receptor 2 gene in a patient with congenital nephrogenic diabetes insipidus.

We have identified a novel mutation of the arginine vasopressin receptor 2 (AVPR2) gene in a case of congenital X-linked nephrogenic diabetes insipidus (NDI). The patient was a 2-mo-old Japanese boy with persistent fever and failure to thrive. He was diagnosed as having congenital NDI by clinical and laboratory findings.

Survival after total joint arthroplasty in patients with rheumatoid arthritis. Comparison of the postoperative life expectancies and survival by initial operative years: 1970s and 1980s group versus 1990s group.

Abstract A total of 867 patients with rheumatoid arthritis (RA) underwent 1764 total joint arthroplasties (total hip arthroplasty and/or total knee arthroplasty) over three decades from 1970 to 1999. A survey on their postoperative survival was conducted in December 2000 in which these patients were divided into two groups. The patients who had their initial arthroplasty in the period 1970 to 1989 were classified as the "70s and 80s group," and those who had their initial arthroplasty from 1990 to 1999 were classified as the "90s group.

[Efficacy of lidocaine on seizures by intravenous and intravenous-drip infusion].

We retrospectively studied the efficacy of intravenous and intravenous-drip infusion administration of lidocaine on seizures treated in Saitama Children's Medical Center during the period of 1997-2002. Thirty eight seizures of 29 children (12 boys and 17 girls, average age 41.4 months) were treated with lidocaine.

RNA expression analysis of a congenital intracranial teratoma.

Congenital intracranial tumors are extremely rare and account only for 0.5%-1.5% of brain tumors in children.

PEGylated adenovirus vectors containing RGD peptides on the tip of PEG show high transduction efficiency and antibody evasion ability.

Background: PEGylation of adenovirus vectors (Ads) is an attractive strategy in gene therapy. Although many types of PEGylated Ad (PEG-Ads), which exhibit antibody evasion activity and long plasma half-life, have been developed, their entry into cells has been prevented by steric hindrance by polyethylene glycol (PEG) chains. Likewise, sufficient gene expression for medical treatment could not be achieved.

Optimal administration dosage of magnesium sulfate for torsades de pointes in children with long QT syndrome.

Background: Intravenous administration of magnesium sulphate (MgSO(4)) is a very effective and safe treatment for torsades de pointes (TdP) associated with acquired long QT syndrome (LQTS) in adults. Discussed here is the efficacy of MgSO(4) for TdP in children with congenital and acquired LQTS.

Methods: The optimal MgSO(4) dosage and serum magnesium (SMg) was determined in six consecutive children with TdP; four had congenital LQTS and two had acquired LQTS.

CFTR gene mutations in Japanese individuals with congenital bilateral absence of the vas deferens.

Congenital bilateral absence of the vas deferens (CBAVD) is a monosymptomatic disease confined to the male reproductive system with similarity to the phenotype of cystic fibrosis (CF), and mutations in the CFTR gene are highly prevalent in Caucasian CBAVD patients. While CF is very rare in Japan, CBAVD is not. Our previous study demonstrated high prevalence of the 5T allele in the CFTR gene in Japanese CBAVD patients.

Widespread gene transduction to the central nervous system by adenovirus in utero: implication for prenatal gene therapy to brain involvement of lysosomal storage disease.

Background: In some lysosomal storage diseases, considerable alterations of the central nervous system (CNS) occur prior to birth and neurodegeneration progresses rapidly soon after birth causing early death in patients. No effective treatment is available after birth. Treatment may need to be initiated before birth to prevent the onset or progression of neurological changes and thereby irreversible brain damage.

High gene expression of the mutant adenovirus vector, both in vitro and in vivo, with the insertion of integrin-targeting peptide into the fiber.

In the present study, a first-generation adenovirus (Ad) vector was modified with the RGD peptide inserted into the fiber. The insertion of an integrin-targeting sequence into the Ad vector notably enhanced the luciferase expression in the Coxsackie virus and Adenovirus Receptor-deficient A2058 and B16BL6 melanoma cells. The results of an in vivo study with tumor-bearing mice also showed that Ad-RGD-Luc had enhanced gene expression in many organs and in the B16BL6 tumor compared to that induced by a conventional Ad vector after intravenous injection.

Brain transplantation of genetically modified bone marrow stromal cells corrects CNS pathology and cognitive function in MPS VII mice.

Current therapies for lysosomal storage diseases (LSDs), enzyme replacement therapy and bone marrow transplantation are effective for visceral organ pathology of LSD, but their effectiveness for brain involvement in LSDs is still a subject of controversy. As an alternative approach, we transplanted genetically modified bone marrow stromal (BMS) cells to lateral ventricle of newborn mucopolysaccharidosis VII (MPS VII) mice. MPS VII is one of LSDs and caused by deficiency of beta-glucuronidase (GUSB), resulting in accumulation of glycosaminoglycans (GAGs) in brain.

Early aerobic training increases end-tidal CO2 pressure during exercise in patients after acute myocardial infarction.

End-tidal CO2 partial pressure (PETCO2) has been suggested as a noninvasive index reflecting cardiac output under constant ventilation. The aim of this study was to examine whether PETCO2 does reflect cardiac output, even during exercise, in patients with acute myocardial infarction (AMI) undergoing exercise training early after onset. Method and Results Patients aged 47-73 years were randomly assigned to either a training group (n=18) or a control group (n=18) 1 week after the onset of AMI.

Inhibition of activin signaling induces pancreatic epithelial cell expansion and diminishes terminal differentiation of pancreatic beta-cells.

Activins regulate the growth and differentiation of a variety of cells. During pancreatic islet development, activins are required for the specialization of pancreatic precursors from the gut endoderm during midgestation. In this study, we probed the role of activin signaling during pancreatic islet cell development and regeneration.

N-octyl-beta-valienamine up-regulates activity of F213I mutant beta-glucosidase in cultured cells: a potential chemical chaperone therapy for Gaucher disease.

Gaucher disease (GD) is the most common form of sphingolipidosis and is caused by a defect of beta-glucosidase (beta-Glu). A carbohydrate mimic N-octyl-beta-valienamine (NOV) is an inhibitor of beta-Glu. When applied to cultured GD fibroblasts with F213I beta-Glu mutation, NOV increased the protein level of the mutant enzyme and up-regulated cellular enzyme activity.

NF-kappaB prevents TNF-alpha-induced apoptosis in an oligodendrocyte cell line.

Nuclear factor kappa beta (NF-kappaB) inhibits apoptosis in sensory, hippocampal, and striatal neurons of the central nervous system. Although several apoptotic stimuli have been shown to activate NF-kappaB in oligodendrocytes, the function of NF-kappaB in this cell type remains unknown. In this study, we introduced plasmids expressing either the p50- or p65-subunit of human NF-kappaB into Central Glia-4 (CG-4)--a rat oligodendrocyte precursor cell line-and determined the influence of NF-kappaB function on tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis.

Treatment of lysosomal storage disorders: cell therapy and gene therapy.

Most lysosomal storage diseases have central nervous system (CNS) involvement. No effective treatment is available at present. We investigated the usefulness of brain-directed gene therapy and cell therapy using mouse models of lysosomal storage diseases.

Neutralizing antibody evasion ability of adenovirus vector induced by the bioconjugation of methoxypolyethylene glycol succinimidyl propionate (MPEG-SPA).

Although adenovirus vectors (Ad) which possesses high transduction efficiency are widely used for gene therapy in animal models, clinical use is very limited. One of the main reason is that nearly 80% of human beings possess anti-Ad antibodies. In this study, we tried to modify Ad with methoxypolyethylene glycol (MPEG) activated by succinimidyl propionate, and, the neutralizing antibody evasion ability of PEGylated Ad was evaluated.

Repression of IFN-gamma expression by peroxisome proliferator-activated receptor gamma.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors expressed in a wide variety of cells. Our studies and others have demonstrated that both human and murine T cells express PPARgamma and that expression can be augmented over time in mitogen-activated splenocytes. PPARgamma ligands decrease proliferation and IL-2 production, and induce apoptosis in both B and T cells.

Constitutionally tall stature with morphological abnormality of the pituitary gland.

We describe two male pubertal cases of constitutionally tall stature (CTS) with an enlarged pituitary gland or pituitary microadenoma. Both patients' basal serum growth hormone (GH) levels were normal. Neither had oversecretion of any other pituitary hormones.

Tumor-suppressive activities by chemokines introduced into OV-HM cells using fiber-mutant adenovirus vectors.

In this study, fiber-mutant adenovirus vectors encoding chemokines, Ad-RGD-mCCL17, Ad-RGD-mCCL21 and Ad-RGD-mCCL22 were constructed. The insertion of integrin-targeting RGD sequence into fiber knob of adenovirus vectors notably enhanced the infection efficiency into tumor cells. Among three chemokine-encoding vectors evaluated, Ad-RGD-mCCL22 showed significant tumor-suppressive activity via transduction into OV-HM cells.

Influence of climate factors on emergency visits for childhood asthma attack.

Background: Asthma attack shows strong seasonality. The purpose of the present study was to quantify the contribution of climate variables and other seasonal factors on the incidence of emergency visits for childhood asthma in Tokyo, Japan.

Methods: The number of children who visited emergency rooms at Jikei university hospitals in Tokyo during 1998-2002 (5559 visits) was retrieved retrospectively from files from the Department of Pediatrics, and compared with 45 climate parameters from the Meteorological Agency using multiple regression models with a stepwise backward elimination approach.

TNFalpha induces rapid activation and nuclear translocation of telomerase in human lymphocytes.

Maintenance of telomeres regulates chromosomal stability and cellular mitosis through a checkpoint mechanism. Continuous cell proliferation requires telomerase to maintain chromosomal stability and to counteract the cellular mitotic clock. Importantly, nuclear expression of telomerase activity is required for elongation of telomere sequences.

Brainstem cranial-nerve lesions in an infant with hypoxic cerebral injury.

Recent studies have revealed that the brainstem is characteristically involved in hypoxic encephalopathy in infants. However, few reports have described clinical and cranial magnetic resonance findings in detail because most patients with brainstem lesions die during delivery or soon afterward. Reported here is a patient who manifested selective brainstem injury caused by perinatal hypoxic cerebral injury and exhibited palsy of the lower-brainstem cranial nerves.