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Biomedical subjects

M Iijima

Publications and source records attributed to M Iijima.

At least 73 records · Page 4Linked to original sources
PubMed1999

A distinct familial presenile dementia with a novel missense mutation in the tau gene.

We report a Japanese family with early onset hereditary frontotemporal dementia and a novel missense mutation (Ser305Asn) in the tau gene. The patients presented with personality changes followed by impaired cognition and memory as well as disorientation, but minimal Parkinsonism. Imaging studies showed fronto-temporal atrophy with ventricular dilatation more on the left, and postmortem examination of the brain revealed numerous neurofibrillary tangles (NFTs) with an unusual morphology and distribution. Silver-stained sections showed ring-shaped NFTs partially surrounding the nucleus that were most prominent in frontal, temporal, insular and postcentral cortices, as well as in dentate gyrus. Cortical NFTs were restricted primarily to layer II, and were composed of straight tubules. Numerous glial cells containing coiled bodies and abundant neuropil threads were detected in cerebral white matter, hippocampus, basal ganglia, diencephalon and brain stem, but no senile plaques or other diagnostic lesions were seen. Both the glial and neuronal tangles were stained by antibodies to phosphorylation-independent and phosphorylation-dependent epitopes in tau. Thus, this novel mutation causes a distinct familial tauopathy.

Adult↗
PubMed1999

FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10.

Missense mutations and intronic mutations in the tau gene cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known missense mutations reduce the ability of tau to promote microtubule assembly. Intronic mutations lead to increased mRNA splicing of the alternatively spliced exon 10, resulting in an overproduction of tau isoforms with four microtubule-binding repeats. We show here that the recently identified FTDP-17 missense mutations N279K and S305N do not reduce the ability of tau to promote microtubule assembly. Instead they lead to increased splicing of exon 10, like the intronic mutations. The N279K and S305N mutations define a class of missense mutations in tau whose primary effects are at the RNA level.

Alternative Splicing↗
PubMed1999

Involvement of a cis-acting element in the suppression of carbamoyl phosphate synthetase I gene expression in the liver of carnitine-deficient mice.

The expression of carbamoyl phosphate synthetase I (CPS) gene is suppressed in the liver of carnitine-deficient juvenile visceral steatosis (JVS) mice at weaning and under starvation at adult age. To clarify the suppression mechanism, we produced CPSL transgenic JVS mice carrying a transgene composed of the chloramphenicol acetyltransferase (CAT) gene with the upstream region (-12 kb to +138) of the rat CPS gene and CPSE transgenic JVS mice carrying a transgene composed of the luciferase gene with minimal promoter (299 bp from -161 to +138) and enhancer (469 bp around -6.3 kb) fragments of the rat gene. The expression of the CAT gene as well as the endogenous CPS was suppressed in CPSL transgenic JVS mice, but luciferase gene expression was not suppressed in CPSE transgenic JVS mice. We isolated the 5'-upstream region of the mouse CPS gene and identified an activator protein-1 (AP-1) site downstream of the minimum enhancer region of both rat and mouse CPS genes. In conjunction with the 313-bp mouse promoter region, the 714-bp mouse enhancer fragment conferred a cell-type-dependent hormone responsiveness. In rat primary cultured hepatocytes, the addition of oleic acid suppressed reporter gene expression induced by dexamethasone in the construct containing the enhancer fragment of 714 bp with the AP-1 site, but not in its AP-1 site mutants or in 519 bp without the AP-1 site. These results strongly suggest that direct protein-protein interaction between AP-1 and glucocorticoid receptor is not involved in the suppression of the CPS gene in JVS mice and that the AP-1 element is the cis-element which is responsible for the suppression.

Animals↗
PubMed1999

Tachycardia as a potential risk indicator for coronary arterial lesions in Kawasaki disease.

UNLABELLED: Tachycardia is frequently observed in the acute phase of Kawasaki Disease (KD) patients. However, little is known about the association between the tachycardia in the acute phase of KD and the development of coronary arterial lesions (CAL). We examined the association between the mean 24 h heart rate in the acute phase of KD observed using 24 h ambulatory ECG monitoring (24 h-ECG) and the occurrence of CAL in patients. In a study conducted between 1994 and 1997, 26 patients with KD underwent 24 h-ECG within the febrile period and before the 9th day of illness. We compared the mean 24 h heart rate based on 24 h-ECG between patients with and those without CAL. Of 26 patients, 7 had CAL. The groups with and without CAL had similar baseline characteristics. The mean 24 h heart rate in the group with CAL was significantly higher than that in the group without CAL (144 +/- 14 vs. 124 +/- 22, P = 0.033). On multiple regression analysis, the mean 24 h heart rate was significantly correlated with the development of CAL (P = 0.019). CONCLUSION: Marked tachycardia detected by 24 h-ambulatory ECG monitoring in the acute phase of Kawasaki disease might provide important information on the development of coronary arterial lesions.

Acute Disease↗
PubMed1999

Antigenic characterization in ampiroxicam-induced photosensitivity using an in vivo model of contact hypersensitivity.

Ampiroxicam (APX), a prodrug of piroxicam (PXM), has been reported to induce photosensitivity. Antigenic characterization of these photosensitivities, however, is still insufficient. The purpose of the present study was to elucidate further mechanism of photosenstivity induced by APX and PXM using an in vivo model of contact hypersensitivity in guinea pigs. Animals sensitized with ultraviolet-A (UVA)-irradiated 1% APX showed positive reaction in the patch testing to UVA-irradiated 1% APX and 1% thiosalicylate (TOS), while they were negative in challenge with UVA-irradiated 1% PXM, non-irradiated APX and PXM, whereas none of UVA-irradiated or non-irradiated APX and PXM showed positive patch test reaction in animals sensitized with UVA-irradiated 1% PXM or control vehicles. Animals sensitized with 1% TOS were successfully challenged by 1% TOS and cross-reacted with UVA-irradiated 1% APX; however, they failed to react with UVA-irradiated PXM, non-irradiated APX and PXM. Indeed, the in vitro study revealed that the concentration of APX was easily reduced by the increase of UVA irradiation dose, as compared with that of PXM. Interestingly, absorption spectrum of UVA-irradiated APX was similar to that of TOS, which is thought to be an active hapten of PXM. In the present study, we succeeded in the development of a novel animal model reflecting the clinical observations. Furthermore, these results suggested that contact hypersensitivity induced by UVA-irradiated APX is developed by photoproducts of APX itself, but not by the biotransformation of APX to PXM.

Animals↗
PubMed1999

The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.

Citrullinaemia (CTLN) is an autosomal recessive disease caused by deficiency of argininosuccinate synthetase (ASS). Adult-onset type II citrullinaemia (CTLN2) is characterized by a liver-specific ASS deficiency with no abnormalities in hepatic ASS mRNA or the gene ASS (refs 1-17). CTLN2 patients (1/100,000 in Japan) suffer from a disturbance of consciousness and coma, and most die with cerebral edema within a few years of onset. CTLN2 differs from classical citrullinaemia (CTLN1, OMIM 215700) in that CTLN1 is neonatal or infantile in onset, with ASS enzyme defects (in all tissues) arising due to mutations in ASS on chromosome 9q34 (refs 18-21). We collected 118 CTLN2 families, and localized the CTLN2 locus to chromosome 7q21.3 by homozygosity mapping analysis of individuals from 18 consanguineous unions. Using positional cloning we identified a novel gene, SLC25A13, and found five different DNA sequence alterations that account for mutations in all consanguineous patients examined. SLC25A13 encodes a 3.4-kb transcript expressed most abundantly in liver. The protein encoded by SLC25A13, named citrin, is bipartite in structure, containing a mitochondrial carrier motif and four EF-hand domains, suggesting it is a calcium-dependent mitochondrial solute transporter with a role in urea cycle function.

Adult↗
PubMed1999

A neuropathological study of dementia in nursing homes in Shimane prefecture, Japan: evaluation of the age and gender effect.

BACKGROUND: Vascular dementia (VD) has been held responsible for the majority of all dementia cases in both epidemiological and neuropathological studies in Japan. The aim of this study was to clarify relative frequencies of dementia neuropathologically in Japanese nursing home residents over a 17-year period and to clarify the gender and age effect on the relative frequencies. METHODS: Three hundred ten aged nursing home residents (146 men and 164 women), including dementia cases in Shimane prefecture, Japan, were evaluated clinically and neuropathologically over a period of 17 years. RESULTS: One hundred twenty-two (48 men and 74 women) of the 310 autopsied (39%) had shown signs of dementia during their lives. In classifying dementia type, Alzheimer's disease (AD) accounted for 34% (41); VD 35% (42); mixed dementia 11% (14); and "other" dementia 20% (25) of all samples. As to the gender and age effect, the most characteristic findings were as follows: (a) There were only VD cases in the 57-69-year-old group; (b) the 70-79 male age group lacked any cases with only AD; (c) more AD than VD was found in elderly men; and (d) in women, AD was the major cause of dementia in total. CONCLUSIONS: VD is responsible for the major cause of dementia in the younger women and the men under 90 years of age; AD is the leading cause of dementia in the elderly men and the women over 79 years of age in nursing homes, Shimane prefecture, Japan.

Age Factors↗
PubMed1999

Multiple fixed drug eruption caused by iomeprol (Iomeron), a nonionic contrast medium.

Most cases of drug eruption caused by nonionic contrast media (NICM) reported to date have been of the erythema multiforme type. Herein we report the first case of multiple fixed drug eruption (FDE) caused by iomeprol (Iomeron(R)). A 67-year-old woman developed multiple pea-sized erythematous papules on the trunk and extremities 4 days after receiving 100 ml of iomeprol for a computed tomography examination. Some of the papules coalesced, forming 7 large plaques on the limbs. Six months later, the patient was mistakenly administered iomeprol again. On the following morning, erythematous plaques admixed with vesicles recurred at the same sites as during the previous episode. In both episodes, the lesions cleared leaving pigmentation that faded with 6 weeks. Both patch testing and an intradermal test with iomeprol on lesional pigmented skin were positive. The present case indicates that NICM may cause multiple FDE and that repeated administration of the causative agent may increase the severity of the eruption.

Aged↗
PubMed1999

Effects of papain on isolation of single smooth muscle cells from the guinea pig longitudinal ileum.

The methods for isolation of single cells from the guinea pig longitudinal ileum were investigated with focussing on the papain concentration for the digestion of the ileum. The ileal muscle was minced. The minced muscle was loaded with fluorescent probes of calcein or fura 2, and treated with papain for 30 min at various concentrations. Papain at concentrations more than 1 U/ml reduced both calcein fluorescence and fura-2-signal evoked by carbachol. Carbachol-induced fura-2-signal was more sensitive to papain than calcein fluorescence, suggesting that proteins related to the formation of receptors are more vulnerable than membrane lipids or proteins limiting the membrane permeability upon the exposure to papain. The resultant yield of single cells was highest at 0.56 U/ml of papain without affecting calcein and fura-2 fluorescence responses, thus this concentration appeared to be appropriate for the isolation of single cells from the ileum. Single cells alive contracted dose dependently by the exposure to carbachol (0.1-10 microM) under the microscopic measurement, and were appeared to grow confluent in culture for approximately 15 days. These results suggest that the low concentration, 0.56 U/ml, of papain in the isolation medium is better to obtain functional cells from the guinea pig ileum.

Animals↗
PubMed1999

[Positivity rate of TTV-DNA in patients with acute liver injury of undetermined etiology].

To elucidate a role of TTV infection in patients with acute liver injury, TTV-DNA in the sera from 97 patients with acute liver injury of various etiology were determined according to Okamoto's method. Out of 77 patients with acute liver injury of determined etiology, 31 patients(40.3%) showed TTV-DNA positive, and out of 15 patients with acute liver injury of undetermined etiology, 8 patients(53.3%) showed TTV-DNA positive. These results suggested no evident role of TTV in patients with acute liver injury was shown. Further study including genotype and quantitative determination of TTV-DNA and antibody assay is needed.

Acute Disease↗
PubMed1999

[The dissecting aortic aneurysm associated with polymyalgia rheumatica: a case report].

We report a patient with a dissecting aortic aneurysm associated with polymyalgia rheumatica (PMR). The patient is a 55-year-old Japanese man without a history of hypertension, diabetes mellitus and syphilis. He was admitted to an emergency hospital because of severe back pain, and was diagnosed as having a dissecting aneurysm of the descending aorta. After the admission, he began to notice severe muscle pain in his bilateral shoulder. Although his back pain gradually improved, his muscle pain progressively worsened, and his lower extremities were also involved. Then, he was introduced to our hospital. On neurological examination, he was alert and oriented. His cranial nerves were all intact. There was no muscle weakness nor sensory disturbance. Laboratory studies revealed that his erhythrocyte sedimentation rate was extremely high without elevation of the serum level of creatine phoshpokinase, rheumatoid factors and c-reactive protein. He was diagnosed as having PMR, and oral administration of prednisolone++ was started. Within several days, his muscle pain dramatically disappeared. As is known, there is a close relationship between PMR and temporal arteritis of giant cell arteritis. In general, PMR is a benign disease and responds well to steroid therapy, and prevalence of the giant cell arteritis is low in Japanese people. However, it should be kept in mind that the dissecting aneurysm is a relevant, severe complication of PMR because arteritis can be latently present in PMR.

Aortic Dissection↗
PubMed1999

[Effect of bufalin on growth and differentiation of human skin carcinoma cells in vitro].

Bufalin, a cardiotonic steroid isolated from the Chinese toad, was previously shown to have growth inhibitory and differentiation inducing activities on leukemia cells and malignant melanoma cells. We examined the effect of bufalin on growth and differentiation of human skin squamous cell carcinoma cells (SSCC-1) in vitro. The concentration needed for growth inhibition of SSCC-1 cells was 10(-8) M, which was lower than those of gamabufotalin and ouabain. When SSCC-1 cells were treated with 10(-8) M bufalin for 16 h, the DNA synthesis of SSCC-1 cells decreased, but there was no change in their survival ratio. The results suggest that growth inhibitory effect of buffalin is not only a cytotoxic effect. Bufalin increased the production of cornified envelopes and the expression of Keratin K10/11 and involurcin. These findings indicate that bufalin has both growth inhibitory and differentiation inducing effects on SSCC-1 cells.

Bufanolides↗
PubMed1999

Differential property of antigenic characterization between piroxicam and ampiroxicam in contact hypersensitivity.

Piroxicam (PXM; a non-steroidal anti-inflammatory drug) has been reported to induce photosensitivity. In our previous report, however, ultraviolet-A (UVA)-irradiated or non-irradiated PXM did not induce any reactions in the in vivo model of contact hypersensitivity, while positive patch testing was shown by ampiroxicam (APX; a prodrug of PXM). The purpose of the present study was to clarify the influence of protein on the antigenicity of PXM using this model. Animals sensitized by UVA-irradiated 1% APX showed positive patch testing (open application) in UVA-irradiated 1% APX, while they were negative in challenge by UVA-irradiated PXM with or without 5% human serum albumin (HSA). Although animals sensitized by 1% thiosalicylate (TOS), which is thought to be an active hapten of PXM, were cross-reacted with UVA-irradiated 1% APX, they failed to react with UVA-irradiated 1% PXM with or without HSA. On the other hand, intra-dermal testing (intra-dermal application) in UVA-irradiated 0.1% PXM with 5% HSA was positive in animals sensitized by UVA-irradiated 1% APX, while 5% HSA alone, 0.1% PXM with 5% HSA and UVA-irradiated 0.1% PXM did not induce any reactions under this condition. Furthermore, concentration of PXM in the presence of HSA was reduced by UVA-irradiation in a time dependent manner, while the degradation of PXM was not observed in the absence of HSA. Finally, PXM almost disappeared at 120 min after the initiation of UVA-irradiation. The degradation of PXM irradiated by UVA was dependent on the concentration of HSA at the range of 0 to 4%. Hence, these results suggest that the presence of protein is necessary for the induction of the antigenic activity of PXM and the antigenic characterization of PXM is different from that of APX in contact hypersensitivity.

Animals↗
PubMed1998

A Dictyostelium discoideum homologue to Tcp-1 is essential for growth and development.

Tcp-1 (t-complex polypeptide 1 gene) was first identified in the mouse as relevant for tail-less and embryonic lethal phenotypes. Since then, its homologous sequences have been isolated in several other species, and the yeast Tcp-1 has been shown to encode a molecular chaperon for actin and tubulin. In a random sample of genes expressed in the gamete of Dictyostelium discoideum (Dd), we encountered a sequence containg the TCP1 motifs. The complete ORF of the gene (DdTcp-1) showed more than 60% similarity to TCP-1 of several organisms, including human. DdTcp-1 was found to be expressed in both sexually mature and immature cells at the growth phase. Although the sexual process itself was not affected, antisense interference of this gene resulted in severe retardation of cell growth, leading to the complete cessation of division. In addition, the antisense transformants stopped asexual development at the finger stage. These results suggest an important function of DdTcp-1 in growth and development of this organism.

Amino Acid Sequence↗