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Biomedical subjects

K Isse

Publications and source records attributed to K Isse.

At least 19 recordsLinked to original sources
PubMed2006

Interferon gamma accelerates NF-kappaB activation of biliary epithelial cells induced by Toll-like receptor and ligand interaction.

BACKGROUND: The Toll-like receptor (TLR) family recognises pathogen associated molecular patterns (PAMPs) and plays a pivotal role in the innate immune response. Biliary epithelial cells (BECs) lining the intrahepatic bile ducts are potentially exposed to bacterial components in bile, and murine BECs possess TLRs that recognise PAMPs, resulting in nuclear factor kappaB (NF-kappaB) activation. AIMS: To examine the presence of TLRs in human BECs and the influence of cytokines and PAMPs on TLR expression and NF-kappaB activation. METHODS: The expression of TLR2-5, MD-2, MyD88, and IRAK1 was examined in human liver tissue and cultured BECs by immunohistochemistry or reverse transcription polymerase chain reaction. The influence of PAMPs (peptidoglycan and lipopolysaccharide) in cultured cells preincubated with interferon gamma (IFNgamma) was evaluated by NF-kappaB activation. RESULTS: TLR2-5, MyD88, and IRAK-1 proteins were detectable in BECs of the intrahepatic biliary tree in human liver tissue. TLR2-5, MD-2, MyD88, and IRAK-1 mRNA was demonstrated in human cultured BECs. The expression of these TLRs was upregulated by IFNgamma, and TLR2 was upregulated by tumour necrosis factor alpha. Interleukins 4 and 6 failed to induce TLR upregulation. Interestingly, preincubation with IFNgamma synergistically increased the upregulation of NF-kappaB induced by PAMPs in cultured BECs. CONCLUSION: These results suggest that the TLR family is present in human biliary cells and participates in the innate immunity of the intrahepatic biliary tree. Disordered regulation of TLRs after intracellular signalling by cytokines and PAMPs may be involved in immune mediated biliary diseases.

Aged↗
PubMed2004

[Lung cancer with ground glass opacity diagnosed by transbronchial lung biopsy using an ultrathin bronchoscope and virtual bronchoscopy].

Although thoracic computed tomography (CT) screening indicated that there are many patients who have pulmonary shadow with ground glass opacity, it is sometimes difficult to obtain the appropriate specimens for histological diagnosis of such patients. We herein report a lung cancer patient with ground glass opacity who was diagnosed preoperatively by an ultrathin bronchoscope and virtual bronchoscopy. A 78-year-old female was admitted to our hospital due to bacterial pneumonia. At the admission, CT showed another abnormal small shadow in her right middle lobe. Since the shadow was not visible by fluoroscopy, we reconstructed the images of virtual bronchoscopy using the data obtained by multidetector CT. The location of the shadow was determined in the peripheral area of a dorsal branch of right B4aialpha. Then the transbronchial lung biopsy using an ultrathin bronchoscope with simultaneous CT guidance was performed. The histological findings of the biopsy specimens revealed that the shadow was highly suspicious for malignancy. Therefore, the right middle lobectomy was conducted, and the tumor was diagnosed as an adenocarcinoma. An ultrathin bronchoscope with virtual bronchoscopy is useful to diagnose a pulmonary shadow with ground glass opacity.

Aged↗
PubMed2001

A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease.

Several lines of evidence have suggested altered functions of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). In the search for polymorphisms in the 5'-flanking and 5'-noncoding regions of the BDNF gene, we found a novel nucleotide substitution (C270T) in the noncoding region. We performed an association study between this polymorphism and AD in a Japanese sample of 170 patients with sporadic AD (51 early-onset and 119 late-onset) and 498 controls. The frequency of individuals who carried the mutated type (T270) was significantly more common in patients with late-onset AD than in controls (P = 0.00004, odds ratio: 3.8, 95% CI 1.9-7.4). However, there was no significant difference in the genotype distribution between the patients with early-onset AD and the controls, although this might be due to the small sample size of the early-onset group. Our results suggest that the C270T polymorphism of the BDNF gene or other unknown polymorphisms, which are in linkage disequilibrium, give susceptibility to late-onset AD. We obtained no evidence for the possible interactions between the BDNF and apolipoprotein E (APOE) genes, suggesting that the possible effect of the BDNF gene on the development of late-onset AD might be independent of the APOE genotype.

Adult↗
PubMed2000

Alzheimer's disease and 5-HTTLPR polymorphism of the serotonin transporter gene: no evidence for an association.

Recently two independent research groups consistently reported a significant association between the serotonin transporter (5-HTT) gene and late-onset sporadic Alzheimer's disease (AD). They found that the "short" allele of the 5-HTT gene-linked polymorphic region (5-HTTLPR), which is associated with reduced transcriptional activity of the gene, increases the risk of developing late-onset AD. The present study tried to replicate this finding in a Japanese sample. We genotyped 41 patients with early-onset AD (<65 years), 82 with late-onset AD, and 336 controls. There was no significant difference in genotype or allele distribution between either patient group and controls in our sample, suggesting that the 5-HTTLPR does not play a major role in the pathogenesis of AD in Japanese.

Age of Onset↗
PubMed2000

No evidence for an association between the Glu298Asp polymorphism of the NOS3 gene and Alzheimer's disease.

Recently a significant association of a missense mutation (Glu298Asp) of the endothelial nitric oxide synthase (NOS3) gene with late-onset Alzheimer's disease (LOAD) was reported. We tried to replicate this finding in a Japanese sample of 121 patients with LOAD, 51 with early-onset AD (EOAD), and 165 medical controls. However, the genotype and allelic distributions for the Glu298Asp polymorphism were similar for these three groups, suggesting that the Glu298Asp polymorphism of the NOS3 gene has no relevance to the development of AD in Japanese.

Aged↗
PubMed2000

Up-regulation of fas ligand at early stages and down-regulation of Fas at progressed stages of intrahepatic cholangiocarcinoma reflect evasion from immune surveillance.

We examined immunohistochemically the possible participation of the Fas/Fas ligand (FasL) system in intrahepatic cholangiocarcinoma (ICC) during the escape from immune surveillance, using 68 cases of ICC, 29 cases of normal intrahepatic large bile ducts, and 18 cases of biliary dysplasia. Apoptosis of tumor-infiltrating lymphocytes (TIL) was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Fas was weakly expressed in normal intrahepatic bile ducts. Almost all biliary dysplasia and well-differentiated ICCs showed moderate to marked expression of Fas, while Fas expression was variable in moderately and poorly differentiated ICCs. Down-regulation of Fas expression was significantly correlated with histologic de-differentiation, vascular invasion, the size of ICCs, and short survival of ICC patients. By in situ hybridization, FasL mRNA were frequently and strongly expressed in biliary dysplasia compared with non-neoplastic intrahepatic bile duct. In well-differentiated ICCs, FasL mRNA expression was frequent and intense. But, the expression gradually decreased in moderately and poorly differentiated ICCs. Down-regulation of FasL mRNA expression in ICCs was correlated with perineural invasion and tumor size (over 4 cm) (P <.05). Apoptotic TIL were more frequent in ICC foci than in non-neoplastic foci remote from ICC foci. These findings suggest that a tumor evasion mechanism involving Fas/FasL exists in ICC; frequent and intense expression of FasL mRNA in well-differentiated ICCs enable them to escape immune surveillance by counterattacking Fas-bearing TIL. This counterattack becomes insensitive in poorly differentiated ICCs, in which the down-regulation of Fas gives them a resistance against the FasL-expressing TIL. These mechanisms may be involved in the tumor progression.

Adult↗
PubMed1998

Possible association of missense mutation (Gly[-63]Glu) of the neurotrophin-3 gene with Alzheimer's disease in Japanese.

Several lines of evidence have suggested a possible involvement of neurotrophic factors in the pathogenesis of neurodegenerative disease. We examined whether a missense mutation (Gly[-63]Glu) of the neurotrophin-3 (NT-3) gene is associated with Alzheimer's disease (AD) in a Japanese sample of 123 patients and 215 controls. We found that homozygotes or heterozygotes for the mutated type (Glu[-63]) were significantly more common among the patients than the controls (P = 0.013, odds ratio 1.77, 95% CI 1.12-2.79). The mutated type was more frequent among the patients than the controls (P = 0.011, odds ratio 1.63, 95%CI 1.11-2.38). This association between NT-3 and AD was more prominent among those who did not carry the epsilon4 allele of the apolipoprotein E gene than those who carried the epsilon4 allele. Our results suggest that the Glu(-63) allele of the NT-3 gene by itself or another mutation nearby which would be in linkage disequilibrium to the mutation is a risk factor for AD.

Adult↗
PubMed1998

Basic and clinical studies on ApoE gene typing by line probe assay (LiPA) as a biological marker for Alzheimer's disease and related disorders: multicenter study in Japan.

The fundamental reagent capability and clinical significance of ApoE gene typing has been investigated. The result of each test shows that the reagent capability satisfied the expected standard. Four-hundred thirty-nine samples classified into three groups (Alzheimer's disease (AD), other types of dementia and nondementia) were measured to examine the clinical significance. The rate of epsilon 4 genotype of each group was 31.5%, 14.6%, 10.4%, respectively. The AD group had a higher rate than the other groups (p < 0.001). The measurement of ApoE genotype is suggested to be useful as one of the guidelines in the diagnosis of AD.

Age Factors↗
PubMed1996

Efficacy of mianserin on symptoms of delirium in the aged: an open trial study.

1. The authors administered the tetracyclic antidepressant mianserin to aged patients with delirium to examine its efficacy in delirium. 2. The subjects were 62 consecutive aged patients with delirium, diagnosed according to DSM-IV. 3. The patients' symptoms of delirium were assessed once a week over the 4-week study period using the Delirium Rating Scale. 4. It was found that mianserin was effective, especially in treating behavioral and sleep-wake disturbance and that it was almost free from undesirable side-effects. It appears to be particularly useful for elderly patients with delirium, who easily develop extrapyramidal side-effects when given antipsychotic drugs. These properties of mianserin are worthy of further study.

Aged↗
PubMed1995

Screening for mutations at codon 717 of the amyloid precursor protein gene in Alzheimer's disease.

Three kinds of missense mutation at codon 717 of amyloid precursor protein (APP) gene (Val --> Ile; Val --> Gly; Val --> Phe) were screened in 114 patients with familial and sporadic Alzheimer's disease (AD), using a rapid testing method for each Val --> Gly and Val --> Phe mutation and Goate's method for Val --> Ile mutation based on the polymerase chain reaction. Mutations were not found in the subjects, confirming earlier suggestions that these three mutations at codon 717 of APP gene account for only a small proportion of cases of not only familial AD but also sporadic AD.

Aged↗
PubMed1995

Incidental Lewy body disease in a patient with REM sleep behavior disorder.

We studied an 84-year-old man with a 20-year history of nocturnal violent behavior during sleep, but no other clinically evident neuropsychiatric disorders. Polysomnographic investigations confirmed that he suffered from REM sleep behavior disorder (RBD). Histopathologic examination revealed he had Lewy body disease with a marked decrease of pigmented neurons in the locus ceruleus and substantia nigra. These histologic findings represent the first documented evidence of a loss of brainstem monoaminergic neurons in clinically idiopathic RBD and suggest that Lewy body disease might provide an explanation for idiopathic RBD in the aged.

Aged↗
PubMed1994

Association of apolipoprotein E4 with sporadic Alzheimer's disease is more pronounced in early onset type.

Apolipoprotein E genotypes in 88 unrelated Japanese patients with NINCDS-ADRDA sporadic Alzheimer's disease (AD) were examined and compared with those of 93 healthy controls. Frequency of epsilon 4 allele was increased in patients with AD (31%) compared with controls (10%), as was reported previously. Individuals homozygous or heterozygous for the allele epsilon 4 had a 5.9-fold increased risk of AD. This tendency was more pronounced in early onset sporadic (= non-familial) type than late onset type. The relative risk was also greater for early onset type (RR = 11.7; 95% CI, 4.9-28.3) than late onset type (RR = 4.3; 95% CI, 2.1-8.8). Moreover, patients with homozygote for the allele epsilon 4 had a 14.7-fold increased risk of early onset sporadic AD (P < 0.005, chi 2 = 9.0, df = 1, 95% CI, 2.5-85.1). Our findings indicated that association of apolipoprotein epsilon 4 with sporadic Alzheimer's disease is more pronounced in early onset type than in late onset type.

Age of Onset↗
PubMed1994

Evaluation of estrogen treatment in female patients with dementia of the Alzheimer type.

This study was designed to investigate the therapeutic efficacy of estrogen in female patients with dementia of the Alzheimer type (DAT). Fifteen DAT patients with a mean age of (mean +/- SE) 71.9 +/- 2.4 years were treated with 0.625 mg of conjugated equine estrogens orally twice a day for 6 weeks. Of the 15 DAT patients, 4 were diagnosed as mild, 7 as moderate and 4 as severe. The effects of estrogen on DAT patients were evaluated by psychometric assessments, behavior rating scales, regional cerebral blood flow (rCBF) measurement and quantitative EEG analysis. Psychometric assessments consisted of Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale (HDS). Dementia syndromes were evaluated by the GBS-Scale (GBSS) and Hamilton Depression Rating Scale (HDRS). During estrogen replacement therapy (ERT), the mean MMSE score (mean +/- SE) increased significantly from 11.6 +/- 1.9 to 13.2 +/- 2.0 at 3 weeks (P < 0.01) and 13.8 +/- 2.0 at 6 weeks (P < 0.001). The mean HDS score increased significantly from 8.6 +/- 2.1 to 11.5 +/- 2.3 at 3 weeks (P < 0.001) and 11.6 +/- 2.6 at 6 weeks (P < 0.01). Significant improvements in the mean scores of the GBSS and HDRS were also observed in the estrogen-treated group, but not in the untreated control group with a mean age of 71.2 +/- 2.5 years (n = 15). The rCBF was measured by single photon emission computed tomography (SPECT). ERT increased the mean rCBF significantly in the lower frontal region (P < 0.01) and primary motor area (P < 0.02) of the right hemisphere. The mean absolute power delta band values in both left and right frontal EEG (Fp1 and Fp2) (P < 0.01) and theta, band values in Fp2 (P < 0.05) decreased significantly during ERT. It is inferred that ERT significantly improves cognitive functions, dementia symptoms, regional cerebral blood flow and EEG activity in female patients with DAT.

Administration, Oral↗
PubMed1994

[A clinical study on memory function in climacteric and periclimacteric women].

This study was designed to investigate memory function in climacteric and periclimacteric women who lived a normal, ordinary life. Two hundred women treated at the gynecological outpatient clinic of Koshigaya Hospital were divided into 7 groups: groups A(31-35 yr), B(36-40 yr), C(41-45 yr), D(46-50 yr), E(51-55 yr), F(56-60 yr) and G(61-65 yr). Each group consisted of 30 women except group G(n = 20). The memory function of each group was determined and the mean scores for 10 paired hard-associates after three trials of presentation were compared. The mean scores (+/- SD) for groups A and B were 8.0 +/- 2.0 and 8.2 +/- 1.7, respectively, which were not statistically different. The scores for both groups were significantly higher than those for the other groups (p < 0.01). The mean scores for groups C and D were 5.9 +/- 2.1 and 5.6 +/- 2.4, respectively, which were not statistically different. The score for group C was significantly higher than those for groups E(4.5 +/- 2.4), F(4.2 +/- 2.2), and G(3.3 +/- 1.6) (p < 0.05). The score for group D was significantly higher than those for groups F and G(p < 0.05). The score for group E was significantly higher than that for group G(p < 0.01). The decrease in memory function was the greatest in group C. In the climacterium, memory impairment was also observed in group E. The former corresponds to the climacteric commencement age group where cyclic changes in serum estrogen levels decrease or cease, and the latter corresponds to the age group for menopause.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Deficiency of fibrinolytic enzyme activities in the serum of patients with Alzheimer-type dementia.

Previously we reported that there is a kallikrein deficiency in the cerebral tissue of patients with Alzheimer-type dementia. The present study was performed to investigate protease changes in the serum of these patients. The results showed that the kallikrein activity was normal, but that the activities of plasmin and urokinase were significantly low. The present findings indicate a derangement in the clotting and fibrinolytic systems in Alzheimer patients.

Aged↗
PubMed1992

[Serum alpha 1-antichymotrypsin in senile dementia].

To evaluate the clinical significance of serum alpha 1-Antichymotrypsin (ACT) as an early diagnostic marker of senile dementia of Alzheimer type (SDAT), we measured 333 healthy and not demented elderly subjects, 27 cases SDAT and 25 cases of vascular dementia (VD). For the measurement, a new high-sensitivity method, double antibody radioimmunoassay method was developed. In healthy elderly subjects, the mean value of serum ACT was 0.229 mg/ml. A tendency towards increase of ACT with aging was noted but was not significant. The serum level of ACT in the SDAT patients was significantly higher (0.309 mg/ml) compared with the healthy elderly subjects and the VD patients (0.226 mg/ml) (p < 0.01). We concluded that in the patients with SDAT, there was an overproduction of ACT and the serum value of ACT was markedly elevated. The measurement of serum ACT is very useful (sensitivity = 88.9%, specificity = 68.7%; cut-off value = 0.250 mg/ml) for the early differential diagnosis of senile dementia.

Aged↗