[Aceruloplasminemia].

Ceruloplasmin is an abundant alpha 2-serum glycoprotein that contains greater than 95% of the copper present in human plasma. It is synthesized mainly in the liver. Aceruloplasminemia is an autosomal recessive disorder affecting iron metabolism, originally called familial apoceruloplasmin deficiency, which manifests late-onset blepharospasm and retinal degeneration.

Relationship among gastric motility, autonomic activity, and portal hemodynamics in patients with liver cirrhosis.

Background And Aims: We examined the effects of the autonomic nervous function and the volume of portal blood flow to clarify the mechanism of the abnormal gastric motility in patients with liver cirrhosis.

Methods: Heart rate variability, electrogastrogram (EGG), and volume of portal blood flow were measured before and after a meal in 27 patients with liver cirrhosis (LC group) and in 20 normal subjects (N group). Autonomic nervous function was evaluated by using spectral analysis of heart rate variability.

[Genotoxicity studies of cefmatilen hydrochloride hydrate (S-1090)].

Cefmatilen hydrochloride hydrate (S-1090), a new non-ester type of orally active cephem antibiotic synthesized in Shionogi Research Laboratories, was evaluated for its genotoxic potential using three assay systems. In a reverse mutation test with bacteria of Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli WP2uvrA using the preincubation method, the number of revertant colonies in the S-1090 treated plates was almost equal to that in the negative control plates in all strains with and without metabolic activation system with S9 mix (maximum dose, 100 micrograms/plate in TA98). In a chromosomal aberration test with cultured Chinese hamster lung cells (CHL/IU), S-1090 did not induce structural chromosome aberrations or polyploid cells either in the absence or presence of S9 mix up to the 50% growth inhibition doses.

A neural network to predict melting temperature (Tm) of RNA duplex.

A straightforward method to predict RNA duplex stability by neural network is described. The best network consists of three layers in which the input layer units are 12 (frequencies of 10 nearest-neighbors and 2 terminals), the hidden layer units are 3 and the output layer unit is 1 (measured Tm). This method to predict Tm has the advantage that the determinations of thermodynamic parameters is not needed.

Voiding dysfunction in a patient with adolescent adrenoleukodystrophy.

The details are reported of bladder dysfunction in a Japanese boy with adrenoleukodystrophy. He developed gait disturbance at the age of 15 years. Spastic paraparesis progressed from the legs to the hands and brain magnetic resonance imaging showed characteristic degenerative change.

Impaired retention of technetium-99m tetrofosmin in hypertrophic cardiomyopathy.

The purpose of this study was to determine whether myocardial imaging using technetium-99m tetrofosmin can noninvasively identify myocardial damage in hypertrophic cardiomyopathy (HC). The study consisted of 10 patients with apical HC, 10 with asymmetric septal HC (ASH) group, 5 with dilated cardiomyopathy (DC)-like group, and 20 healthy subjects. With use of a bull's-eye map of single-photon emission computed tomographic imaging, the total defect score of tetrofosmin and the washout rate were assessed in 5 segments (septum, and anterior, lateral, and inferior walls, and apex) of the left ventricle.

Increased anaerobic glycolysis in mitochondrial trifunctional protein-deficient brain.

Deficiency of mitochondrial trifunctional protein (TP), beta-oxidation enzyme, is characterized by recurrent rhabdomyolysis in adult patients. Positron emission tomography was used to measure brain oxygen (CMRO(2)) and glucose (CMRGlc) metabolisms in an adult patient with TP deficiency who had a homozygous G1331A transition of the beta-subunit gene. The molar ratio of oxygen to glucose consumption showed diffuse reduction; CMRO(2) was markedly decreased, whereas CMRGlc increased.

[Neuronal cell damage in aceruloplasminemia].

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism that causes neurodegeneration of the retina and basal ganglia, as well as diabetes mellitus. The neurological symptoms in affected patients include involuntary movements, ataxia, and dementia reflecting the sites of iron deposition detected by MRI, and the regions of neurodegeneration observed at autopsy. Excess iron functions as a potent catalyst of biologic oxidation.

Stress and coping behavior in patients with diabetes mellitus.

Diabetes mellitus is a disease which must be controlled over the lifetime of a patient. We investigated the issues of stress and coping for diabetes mellitus which may influence self-management. In addition, we examined the association of these factors with blood glucose control, in order to review self-management instructions for diabetes mellitus.

Expression of receptors for glial cell line-derived neurotrophic factor (GDNF) and neurturin in the inner blood-retinal barrier of rats.

The retina is protected from somatic circulation by the blood-retinal barrrier (BRB) composed of tight junctions between retinal vascular endothelial cells (the inner BRB) and those between retinal pigment epithelial cells (the outer BRB). Our recent studies showed that glial cell line-derived neurotrophic factor (GDNF) secreted from astrocytes regulates the permeability of the BBB. In the present study, we immunohistochemically examined the expression of GDNF, neurturin (NTN) and their receptors, GFRalpha1 for GDNF and GFRalpha2 for NTN, because the capillaries of the inner BRB show specialization very similar to the blood-brain barrier (BBB).

Defective electron transfer in complexes I and IV in patients with aceruloplasminemia.

Aceruloplasminemia is a disorder of iron metabolism caused by mutations in the ceruloplasmin gene. It is characterized by progressive neurodegeneration of the retina, basal ganglia, dentate nucleus and cerebral cortex in association with iron accumulation in these tissues. Enzyme activities in the mitochondrial respiratory chain of the cerebral cortices of two patients were reduced to 62% and 71% for complexes I and IV.

Decreased GlcNAc 6-O-sulfotransferase activity in the cornea with macular corneal dystrophy.

Purpose: Macular corneal dystrophy (MCD) is an autosomal recessive inherited disorder that is accompanied by corneal opacity. Explants from MCD-affected corneas have been reported to synthesize low-sulfated KS, suggesting that sulfate groups attached to KS may play critical roles in maintaining corneal transparency. To clear the biosynthetic defect in the MCD cornea, sulfotransferase activities were determined that are presumably involved in the biosynthesis of KS: galactose-6-sulfotransferase (Gal6ST) activity and N-acetylglucosamine 6-O-sulfotransferase (GlcNAc6ST) activity.

Increased lipid peroxidation in the brains of aceruloplasminemia patients.

Aceruloplasminemia is characterized by excessive neurovisceral accumulation of iron due to mutations in the ceruloplasmin gene. We report that the levels of malonaldehyde (MDA) and 4-hydroxynonenals (4-HNE) were elevated both in the frontal cortex and putamen in two patients with aceruloplasminemia compared with those in controls. Immunohistochemical analysis with an antibody raised against HNE-modified protein showed a large number of immunoreactive neurons and glias in the brain of a patient.

Is autonomic dysfunction a necessary condition for chronic peptic ulcer formation?

Background: The relationship between 1/f fluctuation of the heart rate variability and Helicobacter pylori infection was evaluated, in order to clarify whether autonomic nervous dysfunction is a necessary condition for chronic peptic ulcer formation.

Methods: The subjects were 11 patients with recurrent chronic peptic ulcer and 20 age-matched normal subjects. Holter ECGs were recorded over 24 h, and the 1/f(-x) fluctuation of the heart rate was computed.

Evaluation of autonomic nervous function in patients with essential hypertension complicated with peptic ulcer.

Background And Aims: The relationship between peptic ulcer, autonomic activity and the incidence of Helicobacter pylori infection in untreated hypertensive patients complicated with peptic ulcer were evaluated.

Methods: Ten hypertensive patients with peptic ulcer (HT-PU group), 15 untreated essential hypertensive patients without peptic ulcer (HT group) and 10 normal subjects (N group) were enrolled, and a power spectral analysis was performed in each subject. A biopsy urease test was used to detect infection by H.

Age-related changes in the magnitude of ventricular depolarization vector: analyses by magnetocardiogram.

The magnetocardiogram has the beneficial feature that permits the strength and location of the current dipole to be estimated. This study examines the issue of whether the magnitude of the heart current during depolarization phase was influenced by the age of healthy subjects. The magnetocardiograms were recorded by means of a second-derivative SQUID (superconducting quantum interference device) magnetometer (BT Corp, Model BMP, San Diego, CA) in 150 healthy subjects.

Morphologic abnormalities in the brain of chronically hemodialyzed patients without cerebrovascular disease.

In this study, the authors evaluated the cerebral atrophy in 56 chronic hemodialyzed patients, who did not have clinical episodes or radiologic findings of cerebrovascular diseases, and 42 controls. Using computed tomography (CT) images, brain atrophy index (BAI), the proportion of subarachnoidal plus ventricular space in the cranial cavity, and ventricular area index (VAI), percent area of ventricle in the brain, were calculated. CT of the brain demonstrated an age-dependent increase in BAI in both hemodialyzed patients and controls.

A novel mutation (Cys6Gly) in the Cu/Zn superoxide dismutase gene associated with rapidly progressive familial amyotrophic lateral sclerosis.

Autosomal-dominant familial amyotrophic lateral sclerosis (FALS) is associated with mutation in the gene that encodes Cu/Zn superoxide dismutase (SOD1). We identified a novel missense mutation of SOD-1 (Cys6Gly) in exon 1 in a Japanese woman and her family. The illness showed rapid progression similarly to the FALS with a mutation of Cys6Phe that was reported by Morita et al.

Blockade of CTLA-4 signals inhibits Th2-mediated murine chronic graft-versus-host disease by an enhanced expansion of regulatory CD8+ T cells.

CTLA-4 (CD152) is thought to be a negative regulator of T cell activation. Little is known about the function of CTLA-4 in Th2-type immune responses. We have investigated the effect of initial treatment with anti-CTLA-4 mAb on murine chronic graft-vs-host disease.

Evaluation of cardiac function in myocardial infarction patients by ECG 99mTc-MIBI gated SPECT using a three-dimensional perfusion/motion map procedure.

Three-dimensional (3D) radionuclear myocardial imaging has improved the evaluation of left ventricular wall motion. However, there have been no studies evaluating left ventricular function using 3D-perfusion/motion map techniques. We hypothesized that the 3D-perfusion/motion map could accurately evaluate left ventricular wall motion even in patients with a history of myocardial infarction.

Procarbazine genotoxicity in the MutaMouse; strong clastogenicity and organ-specific induction of lacZ mutations.

Procarbazine, a drug used for cancer chemotherapy, is carcinogenic in rodent bioassays. We analyzed the mutagenicity of procarbazine in various organs and the clastogenicity of the drug in hematopoietic cells of the lacZ transgenic MutaMouse. This was part of the second collaborative study of the Mammalian Mutagenesis Study Group of the Japanese Environmental Mutagen Society on the transgenic mouse mutation assay.

Estimation of the gene frequency of aceruloplasminemia in Japan.

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism that causes neurodegeneration of the retina and basal ganglia as well as diabetes mellitus. We screened the serum ceruloplasmin concentrations of 4,990 healthy adult individuals. Subsequent sequence determination of the mutant alleles showed three mutations (5-bp insertion in exon 7, one heterozygote, one-bp deletion in exon 14, two heterozygotes, nonsense mutation in exon 15, one homozygote and two heterozygotes).

A metalloproteinase inhibitor prevents acute graft-versus-host disease in mice after bone marrow transplantation.

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), which is a major complication after allogeneic bone marrow transplantation. We have examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in a murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 to irradiated (BALB/c x C57BL/6) F1 mice that received C57BL/6 bone marrow cells and spleen cells reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues.

A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving the graft-versus-leukaemia effect of allogeneic bone marrow transplantation.

We examined the effect of a hydroxamic acid-based matrix metalloproteinase inhibitor (KB-R7785), which we previously demonstrated to have a potent ameliorating effect on acute graft-versus-host disease (GVHD), and on the graft-versus-leukaemia (GVL) effect of allogeneic bone marrow transplantation (BMT). KB-R7785 was administered to (C57BL/6 x BALB/c) F1 (CBF1) mice that had been inoculated with IgE-producing B53 hybridoma cells of BALB/c origin as a model tumour, along with or without transplantation of C57BL/6 (B6) bone marrow cells and spleen cells (BMS). Administration of KB-R7785 without BMS significantly prolonged the survival of B53-inoculated CBF1 mice by inhibiting the infiltration of B53 cells into the liver and spleen.