Alteration in expression of polyamine and glucose-related enzyme mRNA after small bowel resection in the rat residual ileum.

The adaptive hyperplasia of the residual intestine after a massive bowel resection is not fully understood. We investigated the alterations in polyamine and glucose-related enzyme mRNA expression during intestinal adaptation. Six-week-old male Wistar rats underwent an 80% resection of the small intestine.

Mg2+ transport in the kidney.

Magnesium is abundant in biological systems and an important divalent cation in the human body. Mg2+ helps mediate cellular energy metabolism, ribosomal and membrane integrity. Additionally Mg2+ modulates the activity of several membrane transport and signal transduction systems.

Microsatellite instability in gonadal tumors of XY pure gonadal dysgenesis patients.

To investigate genetic alternation accompanied by malignant transformation in gonadal tumors of XY pure gonadal dysgenesis patients, we investigated microsatellite instability in the hMSH1, hMSH2, TP53, and DCC loci, and ras mutations in two patients. The gonadal tumors from the patients were combined gonadoblastoma and dysgerminoma. Microsatellite instability and/or loss of heterozygotes (LOH) at hMSH1, hMSH2, and TP53 were detected in the dysgerminoma lesions of the both patients, but were not observed in any normal tissues.

Cytokines and neurotrophic factors fail to affect Nogo-A mRNA expression in differentiated human neurones: implications for inflammation-related axonal regeneration in the central nervous system.

Nogo is a novel myelin-associated inhibitor of neurite outgrowth which regulates stable neuronal connections during axonal regeneration following injury in the adult mammalian central nervous system (CNS). Because cytokines and neurotrophic factors play a key role in inflammation-related axonal regeneration, we investigated: (i) the constitutive expression of Nogo and the Nogo receptor (NgR) mRNA in human neural cell lines; (ii) Nogo and NgR mRNA levels in the NTera2 human teratocarcinoma cell line during retinoic acid (RA)-induced neuronal differentiation; and (iii) their regulation in NTera2-derived differentiated neurones (NTera2-N) after exposure to a battery of cytokines and growth factors potentially produced by activated glial cells at post-traumatic inflammatory lesions in the CNS. By reverse transcriptase-polymerase chain reaction analysis, the constitutive expression of Nogo-A, the longest isoform of three distinct Nogo transcripts and NgR mRNA was identified in a wide variety of human neural and non-neural cell lines.

A putative polymorphic Val44Ala variation in the synphilin-1 gene is undetectable in Japanese sporadic Parkinson's disease patients.

Recently, a novel protein-interaction partner of alpha-synuclein, designated synphilin-1, is identified as a constituent of Lewy bodies (LB) in Parkinson's disease (PD) brains. To investigate an involvement of genetic variations of synphilin-1 in development of sporadic PD, a possible single nucleotide polymorphism (SNP) of T131C corresponding to a valine (Val) to alanine (Ala) substitution at codon 44 in exon 3 of the synphilin-1 gene was studied in a Japanese population of 55 patients with sporadic PD and 61 patients with non-PD by direct sequencing analysis. All 116 subjects showed a homozygosity of Val at codon 44 in the synphilin-1 gene, suggesting that this SNP is unlikely to affect genetic susceptibility to sporadic PD in the Japanese population.

Report of the Committee on the classification and diagnostic criteria of diabetes mellitus.

Unlabelled: In 1995, the Japan Diabetes Society (JDS) appointed the Committee for the Classification and Diagnosis of Diabetes Mellitus. The Committee presented a final report in May 1999 in Japanese. This is the English version with minor modifications for readers outside Japan.

Medium-chain triglyceride-rich enteral nutrition is more effective than low-fat enteral nutrition in rat colitis, but is equal in enteritis.

Background: Although enteral nutrition (EN) therapy for Crohn's disease has been confirmed to be as effective as steroid therapy, the precise mechanism responsible for the effects of EN remains unclear, although some of the therapeutic effects of EN are believed to be due to a low dietary fat content. In order to elucidate the influence of fat in EN, it is important to investigate not only the quantity of fat, but also the source of the fat.

Methods: We compared two enteral nutritional formulae: Elental (Ajinomoto) (elemental diet; ED), which contains only 1.

Structure and expression of the glycine cleavage system in rat central nervous system.

The glycine cleavage system (GCS) is a mitochondrial multienzyme system consisting of four individual proteins, three specific components (P-, T-, and H-proteins) and one house-keeping enzyme, dihydrolipoamide dehydrogenase. Inherited deficiency of the GCS causes nonketotic hyperglycinemia (NKH), an inborn error of glycine metabolism. NKH is characterized by massive accumulation of glycine in serum and cerebrospinal fluids and severe neuronal dysfunction in neonates.

Complete suppression of insulitis and diabetes in NOD mice lacking interferon regulatory factor-1.

Interferon regulatory factor-1 (IRF-1), a transcriptional factor, regulates type I interferon and interferon-induced genes. It was reported that IRF-1 regulates important molecules required for inflammation and immune reactions. To investigate the role of IRF-1 in the development of autoimmune diabetes, we established IRF-1 deficient (IRF-1(-/-)) non-obese diabetic (NOD) mice.

A polymorphic variation of serine to tyrosine at codon 18 in the ubiquitin C-terminal hydrolase-L1 gene is associated with a reduced risk of sporadic Parkinson's disease in a Japanese population.

Recent studies suggest that ubiquitin C-terminal hydrolase-L1 (UCH-L1), a neuronal deubiquitinating enzyme, represents a candidate gene responsible for either the development of familial Parkinson's disease (PD) or the protection against sporadic PD in Caucasian populations, although these findings are not fully verified in non-Caucasian populations. To determine an association of the variations in the UCH-L1 gene with development of sporadic PD in a Japanese population, a Ser18Tyr polymorphism and an Ile93Met mutation were studied by PCR-RFLP analysis in 74 Japanese patients with sporadic PD and 155 age-matched non-PD controls. The frequency of 18Tyr allele was significantly lower in PD patients than the controls (38.

Differing effects of IFN beta vs IFN gamma in MS: gene expression in cultured astrocytes.

Background: Recent clinical trials indicate that interferon-beta (IFN beta) is effective in reducing exacerbations in relapsing-remitting MS, whereas IFN gamma provokes acute relapses. However, the molecular mechanisms underlying the beneficial effects of IFN beta and the detrimental effects of IFN gamma in MS remain to be characterized. Previously, the authors showed that IFN beta inhibited IFN gamma-induced major histocompatibility complex (MHC) class II expression on astrocytes.

Alpha-synuclein expression is up-regulated in NTera2 cells during neuronal differentiation but unaffected by exposure to cytokines and neurotrophic factors.

Increasing evidence has indicated that proinflammatory cytokines such as TNF-alpha and IL-1beta, produced by activated microglia and astrocytes, play a key role in progressive degeneration of the nigrostriatal dopaminergic neurons in Parkinson's disease (PD). Since alpha-synuclein is a major component of Lewy bodies in PD brains, we studied the constitutive and cytokine/neurotrophic factor-regulated expression of alpha-synuclein in cultured human neurons by Northern blot and Western blot analyses. The constitutive expression of alpha-synuclein mRNA was identified in a variety of human neural and non-neural cell lines.

Ubiquitin C-terminal hydrolase-L1 (PGP9.5) expression in human neural cell lines following induction of neuronal differentiation and exposure to cytokines, neurotrophic factors or heat stress.

Dysfunction of the ubiquitin-dependent proteolytic pathway contributes to progressive accumulation of ubiquitinated protein inclusions in neurodegenerative disorders, such as Parkinson's disease (PD). Ubiquitin C-terminal hydrolase-L1 (UCH-L1), alternatively designated protein gene product 9.5 (PGP9.

Nicastrin, a key regulator of presenilin function, is expressed constitutively in human neural cell lines.

Nicastrin acts as a key regulator for presenilin (PS)-mediated gamma-secretase cleavage of beta-amyloid precursor protein by forming a functional complex with PS1 and PS2. Both TNF-alpha and IL-1, aberrantly produced by activated microglia and astrocytes, play a role in amyloidogenesis and neurodegeneration in the brains of Alzheimer's disease (AD) patients, while BDNF synthesized chiefly by neurons has been found to be substantially reduced in AD brains. To investigate the constitutive and cytokine/neurotrophic factor-regulated expression of nicastrin in human neural cells, its mRNA levels were studied by RT-PCR and northern blot analysis in SK-N-SH neuroblastoma cells, IMR-32 neuroblastoma cells, U-373MG astrocytoma cells, and NTera2 teratocarcinoma-derived differentiated neurons (NTera2-N) following exposure to TNF-alpha, IL-1beta, BDNF, dibutyryl cyclic AMP, or phorbol 12-myristate 13-acetate.

Neurodegenerative features in developmental brain disorders.

The authors examined the occurrence of neurofibrillary tangles (NFT), senile plaques, spheroids in Goll's nucleus, grumose or foamy spheroid bodies (GFSB) in the basal ganglia, and hyaline inclusions in the brainstem nuclei in 62 patients under 40 years of age with non-progressive developmental brain disorders. Five cases had demonstrated NFT, which tended to be confined to the subcortical nuclei, whereas no senile plaques were identified in any case. Spheroids in Goll's nucleus were significantly increased in three cases of congenital brain anomalies and five cases of perinatal hypoxic ischemic encephalopathy.

Immunohistochemical analysis of brainstem lesions in infantile spasms.

Whether the cerebral or subcortical lesions are involved in the pathogenesis in infantile spasms (IS) remains to be determined. To investigate the functional lesions of the subcortical structures in IS, the brainstem expression of neurotransmitters, neuropeptides and calcium-binding proteins in IS autopsy cases of lissencephaly and of perinatal hypoxic ischemic encephalopathy (HIE/IS) was investigated. The IS patients consisted of four subjects each of lissencephaly and HIE.

Amyloid precursor protein beta-secretase (BACE) mRNA expression in human neural cell lines following induction of neuronal differentiation and exposure to cytokines and growth factors.

Recently, a novel amyloid precursor protein beta-secretase (designated BACE) was identified. Because activated microglia and astrocytes play a role in amyloidogenesis in Alzheimer's disease, the constitutive and glial cytokine/growth factor-regulated expression of BACE was studied in human neural cell lines. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, BACE mRNA expression was identified in various human neural and non-neural cell lines.

Human LT-alpha-mediated resistance to autoimmune diabetes is induced in NOD, but not NOD-scid, mice and abrogated by IL-12.

Systemic administration of human lymphotoxin-alpha (hLT-alpha) made NOD mice resistant not only to spontaneous autoimmune type 1 diabetes mellitus but also to cyclophosphamide (CY)-induced diabetes and diabetes transfer by diabetic NOD spleen cells (triple resistance). In this study we analyzed the mechanisms of hLT-alpha-induced resistance, focusing on (1) hLT-alpha-induced resistance in the pancreatic beta cell, (2) CY-resistant suppressor cells, (3) suppression of induction or function of effector cells for beta cell destruction, or (4) others. To examine the first possibility in vitro, a NOD-derived beta cell line (MIN6N) was pretreated with hLT-alpha and then mixed with diabetic NOD spleen cells and MIN6N cell viability was measured.

A valine to methionine polymorphism at codon 83 in the 8-oxo-dGTPase gene MTH1 is not associated with sporadic Parkinson's disease.

Recently, 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase; MTH1), a key enzyme for preventing oxidative stress-induced DNA damage, has been found to be expressed aberrantly in the nigrostriatal dopaminergic neurones in the brains of those with Parkinson's disease (PD). A valine (Val) to methionine (Met) polymorphism at codon 83 in exon 4 of the MTH1 gene was studied in 73 patients with sporadic PD and 151 age-matched non-PD controls by PCR-RFLP analysis, to determine a possible association of this polymorphism with development of PD. The frequency of either 83Val or 83Met allele was not statistically different between PD patients (92.

Adjuvant-induced improvement of glucose intolerance in type 2 diabetic KK-Ay mice through interleukin-1 and tumor necrosis factor-alpha.

We reported that administration of complete Freund's adjuvant (CFA) improved glucose tolerance test (GTT) results in obese diabetic KK-Ay mice. In this study, we investigated its mechanism. An injection with CFA remarkably improved GTT for more than a week in KK-Ay mice, although insulin response was not changed compared with saline controls.

Middle ear imaging using virtual endoscopy and its application in patients with ossicular chain anomaly.

Virtual endoscopy (VE) is a recently developed technique to provide a realistic surface rendering of various organs, which can be applied to the use of three-dimensional (3D) studies of several lesions. However, its advantages in otological disease have not been well investigated. In this study, we evaluated the application of VE in patients with ossicular chain anomalies.

Determination of urinary 8-epi-prostaglandin F(2alpha) using liquid chromatography-tandem mass spectrometry: increased excretion in diabetics.

Liquid chromatography-tandem mass spectrometry (LC/MS-MS) was applied to the quantitative analysis of urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) level. 8-Epi-PGF(2alpha) and its internal standard, [(2)H(4)]-8-epi-PGF(2alpha), were extracted from urine by using a solid phase extraction cartridge and loaded to LC/MS-MS in selected reaction monitoring (SRM) mode. The standard curve showed good linearity in the range of 40 pg to 10 ng (r = 0.

Beta-catenin expression in human neural cell lines following exposure to cytokines and growth factors.

Beta-catenin acts as a key mediator of the Wnt/Wingless signaling pathway involved in cell proliferation, differentiation and survival. Recent studies have shown that an unstable interaction between beta-catenin and the mutant presenilin-1 induces neuronal apoptosis, and that beta-catenin levels are decreased in the brains of patients with Alzheimer's disease (AD). Since activated microglia and astrocytes play a role in the process of neuronal degeneration in AD, the cytokine/growth factor-regulated expression of beta-catenin in human neural cell lines, including NTera2 teratocarcinoma-derived differentiated neurons (NTera2-N), IMR-32 neuroblastoma, SKN-SH neuroblastoma and U-373MG astrocytoma, was studied quantitatively following exposure to epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, interferon (IFN)-gamma, transforming growth factor (TGF)-beta1, dibutyryl cyclic adenosine 3',5'-cyclic monophosphate (cAMP) (dbcAMP) or phorbol 12-myristate 13-acetate (PMA).

Gene expression profile in prion protein-deficient fibroblasts in culture.

To investigate the physiological function of the cellular isoform of prion protein (PrP(C)), the gene expression profile was studied by analyzing a cDNA expression array containing 597 clones of various functional classes in two distinct skin fibroblast cell lines designated SFK and SFH, established from PrP-deficient (PrP(-)(/-)) mice and PrP(+/+) mice, respectively. The cells were incubated in the culture medium with or without inclusion of basic fibroblast growth factor (bFGF). When SFK cells were compared with SFH cells in untreated conditions, the expression of 15 genes, including those essential for cell proliferation and adhesion, was reduced, whereas the expression of 27 genes, including those involved in the insulin-like growth factor-I (IGF-I) signaling pathway, was elevated.

Modulation of tumor necrosis factor-alpha production with anti-hypertensive drugs.

It is well known that some anti-hypertensive drugs affect insulin sensitivity and that tumor necrosis factor-alpha (TNF-alpha) is a mediator of obesity-associated insulin resistance. In this study, we have investigated the effect of anti-hypertensive drugs, calcium (Ca) channel blockers (amlodipine, manidipine and nicardipine), an alpha(1)-blocker (doxazosin), a beta(1)-blocker (metoprolol), and a thiazide diuretic (hydrochlorothiazide), on lipopolysaccharide (LPS)-induced TNF-alpha production. TNF-alpha production, measured with a bioassay and an immunoassay, was evaluated both in vivo and in vitro, by utilizing mice and a human peripheral blood mononuclear cell culture, respectively.