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I Horiuchi

Publications and source records attributed to I Horiuchi.

At least 19 recordsLinked to original sources
PubMed2002

Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells.

The incidence of distant metastases is higher in the tumours with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumour cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumour cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. Autocrine motility factor inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1alpha, we established hypoxia-inducible factor-1alpha-transfectants and dominant negative hypoxia-inducible factor-1alpha-transfectants. Transfection with hypoxia-inducible factor-1alpha and dominant-negative hypoxia-inducible factor-1alpha enhanced and suppressed the expression of autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA expression and that the disruption of the hypoxia-inducible factor-1 pathway may be an effective treatment for metastasis.

Blotting, Northern↗
PubMed2002

History of allergic disorders in common neurologic diseases in Japanese patients.

OBJECTIVE: To clarify the association between past and present history of allergic disorders and neurologic diseases. METHODS: The past and present history of common allergic disorders together with family history was prospectively studied in all out-patients at the Department of Neurology at Kyushu University Hospital from March 1998 to February 2000. RESULTS: Among 3113 out-patients, 2152 (69.1%) completed a questionnaire. Myelitis showed a statistically significant increase of concomitant atopic dermatitis (P=0.006) and concomitant and past atopic dermatitis (P=0.014), as compared with neurologically healthy controls. Moreover, patients with lower motoneuron disease (LMND) had a statistically significant increase of past and concomitant asthma (P=0.007). None of the other common neurologic diseases showed any increase of allergic disorders when compared with controls. CONCLUSIONS: The present study supports the significant association between allergic disorders and such spinal cord diseases as myelitis and LMND in Japanese patients.

Adolescent↗
PubMed2001

Th2 shift in mononeuritis multiplex and increase of Th2 cells in chronic inflammatory demyelinating polyneuropathy: an intracellular cytokine analysis.

To elucidate the T helper 1 (Th1)/T helper 2 (Th2) balance in various inflammatory neuropathies, we measured the ratio of intracellular interferon-gamma (IFN-gamma)-positive to IL-4-positive cells (intracellular IFN-gamma/IL-4 ratio) by flow cytometry in peripheral blood CD4(+) T cells of 14 patients with mononeuritis multiplex (MNM), 12 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 10 patients with Guillain-Barré syndrome (GBS), 23 patients with neurodegenerative disorders and 36 healthy controls by intracellular labeling. The patients with MNM showed a significantly lower intracellular IFN-gamma/IL-4 ratio (P<0.05) and higher IL-4(+)/IFN-gamma(-) cell percentages (P<0.05) than the controls. The increase of IL-4(+)/IFN-gamma(-) cell percentages was especially prominent in MNM of unknown etiology (P<0.005). The patients with CIDP also showed significantly higher IL-4(+)/IFN-gamma(-) cell percentages (P<0.05) than the controls. The IL-4(+)/IFN-gamma(-) cell percentages were increased in some patients with GBS, but the difference was not significant compared with the controls. Thus, our results suggest that a Th2 shift is a characteristic of MNM and may play an important role in the development of the disease.

Adolescent↗
PubMed2001

Tc1/Tc2 and Th1/Th2 balance in Asian and Western types of multiple sclerosis, HTLV-I-associated myelopathy/tropical spastic paraparesis and hyperIgEaemic myelitis.

CD8+ T cells, like CD4+ T cells, can differentiate into at least two subsets with distinct cytokine patterns: Tc1 cells produce Th1-like cytokines and Tc2 cells produce Th2-like cytokines. To clarify the immunopathological roles of Tc1 and Tc2 cells in central nervous system (CNS) inflammation, we examined intracellular cytokines in CD8+ and CD4+ T cells by flow cytometry and analyzed the Tc1/Tc2 balance as well as the Th1/Th2 balance in 80 patients with various CNS inflammatory diseases, including 20 with optico-spinal multiple sclerosis (OS-MS), 21 with conventional MS (C-MS), 22 with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 17 with hyperIgEaemic myelitis. Twenty-two healthy subjects were also examined as controls. Patients with OS-MS showed a significantly higher percentage of INF-gamma+IL-4- CD8+ T cells as well as CD4+ T cells and a significantly higher intracellular interferon-gamma (IFN-gamma)/interleukin-4 (IL-4) ratio both in CD8+ and CD4+ T cells throughout the relapse and remission phases than the healthy controls. Furthermore, the patients with OS-MS showed a significantly lower percentage of INF-gamma-IL-4+ CD4+ T cells as well as CD8+ T cells during the relapse phase than the healthy controls. On the other hand, the patients with C-MS showed a significantly higher percentage of IFN-gamma-IL-4+ CD8+ T cells in addition to more IFN-gamma+IL-4- CD4+ T cells during the relapse phase than the healthy controls. The HAM/TSP patients showed a significantly higher percentage of INF-gamma+IL-4- CD8+ T cells and a significantly higher intracellular IFN-gamma/IL-4 ratio in CD8+ T cells than the healthy controls. In contrast, in hyperIgEaemic myelitis, in addition to a significantly lower intracellular IFN-gamma/IL-4 ratio in CD4+ T cells, a tendency toward a lower intracellular IFN-gamma/IL-4 ratio in CD8+ T cells in comparison to the healthy controls was observed. These results clarified for the first time the distinct Tc1/Tc2 balance in each disease condition as follows: Tc1 cell response is predominant in OS-MS and HAM/TSP, while Tc2 cell response is predominant in hyperIgEaemic myelitis and at relapse phase of C-MS. Furthermore, our results suggest that CD8+ T cells play an adjunctive role in disease induction and the clinical course of MS.

Adult↗
PubMed2001

Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation.

Hypovasculature is an outstanding characteristic of pancreatic cancers in imaging diagnosis, suggesting that blood supply is poor in pancreatic cancer tissues. Despite poor blood supply, pancreatic cancer cells survive and proliferate in severe hypoxia and nutrient deprivation. To demonstrate how pancreatic cancer cells adapt themselves to hypoxia and nutrient deprivation, we investigated the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) protein and HIF-1-inducible genes in human pancreatic cancer cell lines in comparison with other cancer cell lines. We found that HIF-1alpha protein was constitutively expressed in 15 of 20 pancreatic cancer cell lines (75%) but in none of other cancer cell lines tested in this study. The cells with constitutive expression of HIF-1alpha were more resistant to apoptosis induced by hypoxia and glucose deprivation than those without constitutive expression of HIF-1alpha. Transfection with HIF-1alpha transformed the latter cells resistant to apoptosis and increased in vivo tumorigenicity. Furthermore, anaerobic metabolism-associated genes, Glut1 and aldolase A, were more highly expressed in the cells with constitutive expression of HIF-1alpha than in the cells without it. These results suggest that constitutive expression of HIF-1alpha contributes to the survival and proliferation of pancreatic cancer cells in hypoxia and glucose deprivation through the activation of anaerobic metabolism.

Animals↗
PubMed2001

Spinal cord lesions of myelitis with hyperIgEemia and mite antigen specific IgE (atopic myelitis) manifest eosinophilic inflammation.

We report the neuropathological findings of spinal cord specimens obtained from two patients who had localized myelitis with hyperIgEemia and mite antigen specific IgE (atopic myelitis). Both cases showed mild spinal cord dysfunction, and the gadolinium-enhanced area of the isolated spinal cord lesion observed on MRI was biopsied, respectively. Neuropathologically, both cases showed many perivascular lymphocyte cuffings associated with disrupted vessels, and the infiltration of eosinophils in the spinal cord lesions. Both myelin and axons were lost in the lesions, which were associated with astrogliosis. These findings suggest that an allergic mechanism may play a role in this condition.

Adult↗
PubMed2001

Suppression of transthyretin expression by ribozymes: a possible therapy for familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy type 1 (FAP) is an autosomal-dominantly inherited disorder with systemic deposition of a variant transthyretin (TTR). We attempted to suppress TTR production by ribozyme degradation of TTR mRNA. Hammerhead and hairpin ribozymes cleaved TTR mRNA at specific individual sites in vitro. A ribozyme targeting a variant TTR (E61K) degraded the variant mRNA, but not a wild-type mRNA. These ribozymes also reduced the amounts of TTR mRNA and protein in HepG2 cells and COS-1 cells transfected with TTR-E61K cDNA. Ribozymes might be studied further as a potential treatment for FAP.

Amyloid Neuropathies↗
PubMed2001

Myelitis associated with atopic disorders in Japan: a retrospective clinical study of the past 20 years.

OBJECTIVE: To clarify the clinical features of myelitis associated with atopic disorders in Japanese patients. SUBJECTS AND METHODS: We retrospectively studied the clinical, immunological and electrophysiological features of 68 consecutive patients with myelitis of acute or subacute onset diagnosed at Kyushu University Hospital during the past 20 years. RESULTS: While only 2 of 28 (7%) patients with myelitis diagnosed between 1979 and 1993 had either atopic dermatitis (AD) or bronchial asthma (BA), 19 of 40 (48%) patients with myelitis diagnosed between 1994 and 1998 did. Among the 40 patients with myelitis diagnosed between 1994 and 1998, 19 patients with either AD or BA as well as 21 patients without either disease showed a significantly higher level of serum total IgE, higher frequency of hyperIgEaemia and higher frequency of mite antigen-specific IgE than 82 healthy controls. Myelitis patients with AD presenting as persistent paresthesia/dysesthesia in all four limbs showed cervical cord lesions on MRI and abnormalities in upper limb motor evoked potentials but no abnormalities in the cerebrospinal fluid (CSF), while myelitis patients with BA showed preferential involvement of the lower motor neurons clinically and electromyographically. In addition, 12 patients with myelitis who had hyperIgEaemia and mite antigen-specific IgE but neither AD nor BA showed incomplete transverse myelitis with mild motor disability and few CSF abnormalities. CONCLUSION: The clinical features of myelitis associated with atopic disorders were in part distinguished by the type of preceding atopic disorder, and also were different from those of hyperIgEaemic myelitis with no preceding atopic disorders.

Adult↗
PubMed2001

[Epilepsy in patients with severe motor and intellectual disabilities: a long-term follow-up].

Long-term prognosis of epilepsy was investigated on 117 institutionalized patients with severe motor and intellectual disabilities, who were above 15 years of age in 1977, for a 20-year-period from 1977 to 1997. The incidence of epilepsy was 64.1% (75 patients), which was active in 28 patients (37.3%). The patients with the most severe psychomotor disabilities (bedridden and DQ < 20) showed the highest incidence of epilepsy (85.0%). Patients who died during the follow-up period showed higher incidence of active epilepsy (p < 0.01). During the follow-up of 94 surviving patients, persistence, relapse, and onset of seizures were frequent in patients with most severe intellectual disability, whereas those with less severe intellectual disability (20 < DQ < 35) were all seizure-free. Twenty-one patients had active epilepsy; symptomatic partial epilepsy in 17 (81.0%) and generalized epilepsy in 4 (19.0%). Notably, 5 of the 6 patients with persistent frequent seizures had age-dependent epileptic encephalopathy; persistent Lennox-Gastaut syndrome (LGS) (2 patients), severe epilepsy with multiple independent spike foci evolved from West syndrome (WS) and LGS (2 patients), and partial epilepsy with the history of LGS (1 patient).

Adolescent↗
PubMed2001

[A new predictive formula for anterior chamber depth for pseudophakia].

PURPOSE: To develop a new predictive formula of the anterior chamber depth(ACD) of the pseudophakic eyes for more accurate intraocular lens(IOL) power calculation with the Ray Tracing method. METHODS: We studied a series of 149 phacoemulsificated eyes with capsulorhexis and in-the-bag fixation of IOL. ACD was measured with a Jaeger type depth measuring unit which was attached to a slit-lamp biomicroscope. We developed the formula with 3 variables: preoperative anterior corneal curvature with keratometer, and ACD and crystalline lens thickness with preoperative ultrasonography. We named the derived formula "formula H". We compared formula H with Olsen's predictive formula for the ACD(Olsen 92, Olsen 95). RESULTS: Mean absolute error between the predicted and postoperatively measured ACD was 0.174 +/- 0.133, 0.280 +/- 0.235, 0.229 +/- 0.200 mm in formula H, Olsen 92, and Olsen 95, respectively. Formula H was significantly more accurate than both Olsen formulas(p < 0.001, p < 0.05, respectively). CONCLUSIONS: The accuracy of IOL power calculation can be improved with the new formula using the Ray Tracing method, using the new ACD predictve formula.

Aged↗
PubMed2001

[A new theoretical formula for the intraocular lens power calculation by the Ray Tracing Method].

PURPOSE: To study the mathematical properties of the intraocular lens(IOL) power calculation with the Ray Tracing method and to investigate its clinical results. METHODS: We first obtained a ray focusing equation with the Ray Tracing method, and then derived an emmetropizing equation and an equation for postoperative refraction. The exact calculation of these equations was investigated. A new IOL power calculation formula was consequently developed and named "formula H", combining it with the predictive formula for the postoperative anterior chamber depth of pseudophakic eyes in another report by us. A series of 150 phacoemulsificated eyes with capsulorhexis and in-the-bag fixation of IOL were studied. The cases were divided into 3 groups; 16 short eyes(< 22 mm), 103 normal eyes(22 < or = and < 24.5 mm), and 31 long eyes(> or = 24.5 mm). The predictive error of formula H was compared with that of SRK-T, Holladay, and SRK II in each group. RESULTS: The exact calculation of emmetropizing power in taking account of a IOL design was mathematically impossible, or generally difficult. In the latter case, however, we could calculate it by solving a cubic or quartic equation. Exact and easy predictive calculation of postoperative refraction for any IOL design was possible if we knew such data as anterior and posterior curvature and thickness of each power of IOL. The mean absolute error of formula H was 0.38, 0.34, 0.36, 0.44 diopter, in all eyes, short eyes, normal eyes, and long eyes, respectively. Formula H was significantly more accurate than all other formulas in all eyes, in short eyes and normal eyes. CONCLUSIONS: For clinical use, predictive calculation of postoperative refraction should be recommended but calculation of emmetropizing power should be abandoned. But emmetropizing calculation is useful and important for the fundamental study of IOL power calculation. Formula H was more accurate than all other formulas and very useful for clinical use.

Anterior Chamber↗
PubMed2001

[Diffusion-weighted imaging of brain death: study of apparent diffusion coefficient].

DWI(Diffusion-weighted images) of the brain has been revealed to be useful in diagnosis of several clinical conditions. However, little is known about DWI with regard to brain death. We had opportunities to study patients with brain death. Case 1. A 34-year-old woman experienced cardiopulmonary arrest due to severe ventricular fibrillation, and resuscitated after about 120 minutes. After brain death, DWI showed high signals in the cerebral cortex, putamen, thalamus, brain stem and cerebellum, and ADC(apparent diffusion coefficient) values were 30-40% lower than those of normal volunteers. Case 2. A 45-year-old woman experienced cardiopulmonary arrest due to pontine hemorrhage, and was resuscitated after about 20 minutes. Before brain death, DWI showed high signals in the cerebral cortex, putamen, thalamus, brain stem and cerebellum, and ADC values were the same as those of normal volunteers. After brain death, DWI showed more clearly defined in these areas, but ADC values were 30-40% lower than the first values. DWI and ADC mapping shows areas corresponding to edema of a cytotoxic nature and to ischemic tissue. The characteristic views of high signals in the whole area of the brain were present, and an objective evaluation was possible with DWI after the brain death diagnosis by measuring ADC values.

Adult↗
PubMed2000

Flow cytometric differentiation of Asian and Western types of multiple sclerosis, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and hyperIgEaemic myelitis by analyses of memory CD4 positive T cell subsets and NK cell subsets.

We examined the alterations of memory CD4(+) T cell subsets bearing surface receptors linked to either Th1 or Th2 cytokine production as well as natural killer (NK) cell subsets by three color flow cytometry in the peripheral blood from 36 patients with clinically definite multiple sclerosis (MS), 27 patients with HAM/TSP, 13 patients with hyperIgEaemic myelitis who had mite antigen-specific IgE and 25 healthy controls (HC). The patients with MS were clinically classified into an optico-spinal form of MS (Asian type, MS-A) and the conventional form of MS (Western type, MS-W). MS-A showed a significant increase of CD4(+)CD45RA(-)CCR5(+) cells (Th1 cells) through the relapse and remission phases in comparison to HC, while MS-W showed a significant increase of CD4(+)CD45RO(+)CD62L(-) cells (Th1 cells) only at the relapse phase. HAM/TSP showed a significant increase of CCR5(+) and CD62L(-) memory CD4(+) T cells as well as CD30(+) memory CD4(+) T cells (Th2 cells) in comparison to HC. On the other hand, a selective increase of CD4(+)CD45RO(+)CD30(+) cells was found in hyperIgEaemic myelitis. The percentage of mature NK cells (CD3(-)CD16(+)CD56(+) cells) as well as double negative T cells (CD3(+)CD4(-)CD8(-) cells) decreased significantly in HAM/TSP in comparison to HC. Our findings therefore suggest a flow cytometric analysis of Th1/Th2-associated markers on memory CD4(+) T cells as well as NK cell subsets to be useful for differentiating various inflammatory neurologic conditions.

Adult↗
PubMed2000

Th1 dominance in HAM/TSP and the optico-spinal form of multiple sclerosis versus Th2 dominance in mite antigen-specific IgE myelitis.

To clarify the Th1/Th2 balance in spinal cord inflammation, we used ELISA to measure the total and allergen-specific IgE in 69 patients with clinically definite multiple sclerosis (MS), including 24 patients with the optico-spinal form of MS, 45 with HAM/TSP, 30 HTLV-I carriers without HAM/TSP, 40 patients with acute myelitis, 43 with neurodegenerative disorders, and 42 healthy subjects, and flow cytometry to study the intracellular IFNgamma-positive versus IL-4-positive cell ratio (intracellular IFNgamma/IL-4 ratio) in peripheral blood CD4(+) T cells in 40 patients with MS, including 17 patients with the optico-spinal form of MS, 23 with HAM/TSP, 22 with acute myelitis, 23 with neurodegenerative disorders, and 36 healthy subjects. Patients with HAM/TSP showed a significantly higher intracellular IFNgamma/IL-4 ratio, lower IL-4(+)/IFN-gamma(-) cell percentages, lower total IgE level, and lower frequency of cedar pollen-specific IgE than did the controls. The patients with optico-spinal MS showed a significantly higher intracellular IFNgamma/IL-4 ratio and higher IL-4(-)/IFN-gamma(+) cell percentages than the controls even at remission or in the convalescence phase. In contrast, in the patients with acute myelitis, the total serum IgE level and the frequency of mite antigen-specific IgE were significantly elevated in comparison to the controls, while those having mite antigen-specific IgE myelitis showed a significantly lower IFNgamma/IL-4 ratio in the CD4(+) T cells in comparison to the controls. These findings suggest that the Th1 cell response is predominant in HAM/TSP and optico-spinal MS, whereas the Th2 cell response is predominant in mite antigen-specific IgE myelitis.

Adult↗
PubMed2000

Both the HLA-CPB1 and -DRB1 alleles correlate with risk for multiple sclerosis in Japanese: clinical phenotypes and gender as important factors.

The purpose of this study was to clarify the association of HLA-DRB1 and -DPB1 alleles with multiple sclerosis (MS) in Japanese, to determine whether optico-spinal MS (OS-MS) and conventional MS are immunogenetically distinct, and to verify the role of gender difference in HLA associations of MS. We studied HLA-DRB1 and -DPB1 polymorphisms in 166 Japanese patients with MS. Forty-seven patients were classified as having the optico-spinal MS (OS-MS) and 119 as having conventional MS. A lack of DPB1*0301 and a higher frequency of DPB1*0501 compared with controls (corrected P<0.0074; odds ratio=9.48) were found in OS-MS. By contrast, we found for the first time an association of DPB1*0301 with conventional MS in Japanese (corrected P=0.0444; odds ratio=3.28). Logistic analysis, adjusted for sex and age, revealed independent associations of DPB1*0301 (P=0.0004, adjusted odds ratio (aOR)=4.70), DPB1*0501 (P=0.0081, aOR= 2.50) and DRB1*1501 (P=0.0252, aOR=2.21) with conventional MS. However, the frequencies of DRB1*1501 and DPB1*0501 in male patients with conventional MS were equal to those in male controls while the DPB1*0301 frequency was increased in both male and female patients. We did not find any association of these HLA alleles with disease course and severity. In conclusion, OS-MS is a DPB1*0501-associated distinct subtype of MS, and DPB1*0301 is the most strongly associated allele with conventional MS in Japanese. In addition, gender plays an important role in HLA association with MS.

Alleles↗