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Biomedical subjects

M Yamada

Publications and source records attributed to M Yamada.

At least 55 records · Page 3Linked to original sources
PubMed2005

Decreased tear lipocalin concentration in patients with meibomian gland dysfunction.

BACKGROUND/AIM: Recent studies have demonstrated that tear lipocalin (TL) and phospholipids have a crucial role in maintaining tear film stability. The level of TL in patients with meibomian gland dysfunction (MGD) was examined and these data were correlated with the severity of their clinical disorder. METHODS: 12 patients with obstructive MGD, 12 patients with seborrhoeic MGD, and 12 age matched normal control subjects participated in this study. 3 mul of unstimulated tears were collected with a micropipette from the inferior tear meniscus in the right eye of all subjects. Tear samples were fractionated by high performance liquid chromatography, and TL concentrations were assayed with a bicinchoninic acid technique. RESULTS: The mean concentration of TL in patients with obstructive and seborrhoeic MGD was significantly lower than in normal controls. TL concentration correlated positively with tear film break up time and negatively with fluorescein staining scores. CONCLUSION: These results suggest that TL deficiency may be a predisposing factor for the manifestation of symptoms in MGD.

Aged↗
PubMed2005

Lactoferrin Glu561Asp facilitates secondary amyloidosis in the cornea.

AIM: To elucidate the pathogenic mechanism of amyloid formation in corneal amyloidosis with trichiasis. METHODS: Ophthalmological examination was performed in nine patients to determine secondary corneal amyloidosis with trichiasis. Congo red staining and immunohistochemistry using anti-human lactoferrin antibody were used for biopsied corneal samples. For genetic analyses, single strand conformation polymorphism (SSCP), direct DNA sequence analysis, and polymerase chain reaction (PCR) induced mutation restriction analysis (IMRA) were employed to detect lactoferrin gene polymorphism. RESULTS: All patients had had trichiasis at least for 1 year, and all amyloid-like deposits were found in one eye with trichiasis. Ophthalmological examination revealed that eight patients showed gelatinous type of amyloid deposition and one showed lattice type of amyloid deposition. Studies of biopsied corneal samples with Congo red stain revealed positive staining just under the corneal epithelial cells. Immunoreactivity of anti-human lactoferrin antibodies was recognised in all tissues with positive Congo red staining. Lactoferrin gene analysis revealed that seven patients were heterozygotic and two were homozygotic for lactoferrin Glu561Asp. The frequency of the polymorphism in the patients was significantly different from that in 56 healthy control subjects. CONCLUSION: Lactoferrin Glu561Asp is a key polymorphism related to facilitating amyloid formation in corneal amyloidosis with trichiasis.

Adolescent↗
PubMed2005

The p53-Mdm2 association in epithelial cells in idiopathic pulmonary fibrosis and non-specific interstitial pneumonia.

BACKGROUND: Wild-type p53 is increased during cellular responses to various stresses. Mdm2, which is induced by p53, regulates p53 protein concentrations through the ubiquitin-proteasome pathway. AIM: To investigate whether the Mdm2 mediated ubiquitination of p53 is associated with epithelial cell apoptosis in idiopathic pulmonary fibrosis (IPF). METHODS: Immunohistochemistry and western blot analysis were carried out on lung samples obtained by lung biopsy from patients with IPF and non-specific interstitial pneumonia (NSIP). RESULTS: The expression of p53, phosphorylated p53, Mdm2, p21, and Bax was upregulated in epithelial cells from patients with IPF and NSIP compared with normal lung parenchyma. Except for p21, there was a significant increase in the expression of these factors in IPF compared with NSIP. In addition, the number of apoptotic cells and the number of p53 and Bax positive cells was increased compared with controls. p53 conjugated with Mdm2 was decreased in IPF compared with NSIP and controls. Ubiquitinated p53 was increased in both IPF and NSIP compared with controls. CONCLUSIONS: Signalling molecules associated with p53 mediated apoptosis may participate in epithelial cell apoptosis, and the attenuation of p53-Mdm2 conjugation and of p53 degradation may be involved in the epithelial cell apoptosis seen in IPF. Augmented epithelial apoptosis in IPF may lead to the poor prognosis compared with NSIP.

Adult↗
PubMed2005

Association of a polymorphism of the transforming growth factor-beta1 gene with cerebral amyloid angiopathy.

BACKGROUND: A recent study showed that transforming growth factor-beta1 (TGF-beta1) induces amyloid-beta deposition in cerebral blood vessels and meninges of a transgenic mouse model of Alzheimer's disease (AD), and that TGF-beta1 mRNA levels are correlated with cerebral amyloid angiopathy (CAA) in human AD brains. A T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 gene has been reported to be associated with the serum TGF-beta1 concentration. We investigated whether the TGF-beta1 polymorphism is associated with the risk of CAA. METHODS: The association between the severity of CAA and the T/C polymorphism at codon 10 in exon 1 of the TGF-beta1 was investigated in 167 elderly Japanese autopsy cases, including 73 patients with AD. The apolipoprotein E (APOE) genotype was also determined. RESULTS: The genotypes (TT/ TC/ CC) were associated with the severity of CAA significantly in all patients (p = 0.0026), in non-AD patients (p = 0.011), and APOE non-epsilon4 carriers (p = 0.0099), but not in AD patients or APOE epsilon4 carriers. The number of the T alleles positively correlated with the severity of CAA in all patients (p = 0.0011), non-AD patients (p = 0.0026), and APOE non-epsilon4 carriers (p = 0.0028), but not in AD patients or APOE epsilon4 carriers. The polymorphism was not significantly associated with AD. CONCLUSIONS: Our results suggest that the polymorphism in TGF-beta1 is associated with the severity of CAA, especially in non-AD patients and APOE non-epsilon4 carriers.

Aged↗
PubMed2005

Involvement of the peripheral nervous system in human prion diseases including dural graft associated Creutzfeldt-Jakob disease.

OBJECTIVE: To investigate abnormal prion protein (PrP) deposition in the peripheral nervous system (PNS) in human prion diseases. METHODS: Eight patients with prion diseases were examined: three with sporadic Creutzfeldt-Jakob disease (sCJD), two with dural graft associated CJD (dCJD), one with Gerstmann-Straussler-Scheinker disease (GSS) with a PrP P102L mutation (GSS102), and two with a P105L mutation (GSS105). An atypical case of sCJD with PrP plaques in the brain presented clinically with peripheral neuropathy, and showed demyelination in 12% of the teased fibres of the sural nerve. The PNS was investigated by immunohistochemical and western blotting analyses of PrP. RESULTS: In immunohistochemical studies, granular PrP deposits were detected in some neurones of dorsal root ganglia and a few fibres of peripheral nerves and spinal posterior roots in one sCJD and two dCJD patients, but not in GSS102 or GSS105 patients. The atypical case of sCJD with peripheral neuropathy showed no obvious PrP deposition in the nerves. Western blotting analysis of the PNS from the dCJD patients revealed a small amount of protease K resistant PrP in the dorsal root ganglia and peripheral nerves. CONCLUSIONS: Abnormal PrP deposition occurs in the dorsal root ganglia and peripheral nerves in sCJD and dCJD. The PrP deposits in the PNS are not correlated with clinical manifestation of peripheral neuropathy in CJD.

Adult↗
PubMed2005

Increased circulating endothelial progenitor cells in patients with bacterial pneumonia: evidence that bone marrow derived cells contribute to lung repair.

BACKGROUND: Tissue repair often occurs in organs damaged by various inflammatory diseases including pneumonia. Inflammatory stimuli induce a rapid and massive release of inflammatory cells from the bone marrow. Recent studies have suggested that bone marrow cells have the potential to differentiate into a variety of cell types. It has been shown that administration of lipopolysaccharide (LPS) to murine lungs induces a rapid release of endothelial progenitor cells (EPCs) into the circulation, and that bone marrow derived progenitor cells including EPCs contribute to lung repair after lung injury in mice. This study was undertaken to investigate the mobilisation of EPCs in humans following acute pneumonia. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood taken from 23 patients with pneumonia during both the acute and convalescent phase. 1x10(6) PBMCs were plated on fibronectin coated culture slides and cultured in culture medium for endothelium. The numbers of EPCs were counted 8 days after plating. RESULTS: The number of circulating EPCs significantly increased in patients with pneumonia (p<0.0001). Patients with low EPC counts tended to have persistent fibrotic changes in their lungs even after their recovery from pneumonia. CONCLUSIONS: Inflammatory stimuli induce a rapid release of EPCs into the circulation in humans. A sufficient number of EPCs is necessary for proper lung repair following bacterial pneumonia.

Aged↗
PubMed2005

Apoptosis signaling pathways in lung diseases.

Evidence that apoptosis plays an important role in the pathophysiology of lung diseases has been accumulated. Apoptosis signaling is classically composed of two principle pathways. One is a direct pathway from death receptor ligation to caspase cascade activation and cell death. Death receptor ligation triggers recruitment of the precursor form of caspase-8 to a death-inducing complex, through the adaptor protein FADD, which leads to caspase-8 activation. The other pathway triggered by stimuli such as drugs, radiation, infectious agents and reactive oxygen species is initiated in mitochondria. After cytochrome c is released into the cytosol from the mitochondria, it binds to Apaf1 and ATP, which then activate caspase-9. Recently, endoplasmic reticulum has also been shown to be the organelle to execute apoptosis. Further understanding of molecular mechanisms of apoptosis and its regulation by novel drugs may lead to the development of effective strategies against lung diseases. We overview the signaling pathways of apoptosis and discuss the involvement of apoptosis in the pathophysiology of various lung diseases.

Animals↗
PubMed2004

Hereditary spastic paraplegia with frontal lobe dysfunction: a clinicopathologic study.

The authors report an unusual family with hereditary spastic paraplegia (HSP) with frontal lobe dysfunction having the onset in the sixth decade. All the patients showed hypoperfusion in the frontal lobes and thalami on SPECT. Neuropathologic findings revealed thin corpus callosum and degeneration in the thalamic dorsomedial nuclei as well as degeneration of the corticospinal tracts. This family was likely affected by a novel form of HSP characterized by frontal lobe dysfunction caused by thalamic degeneration.

Adult↗
PubMed2004

Spatiotemporal patterns of movement-related fields in stroke patients.

In this study, brain functions in stroke patients and normal subjects were analyzed by observing neuromagnetic fields during button pressing tasks. The measurements included force measurement, visual stimuli presentation and magnetoencephalography (MEG). A 122-channel whole-head MEG system (Neuromag 122) was used. A total of 18 subjects (11 post-stroke and 7 control subjects) participated in the study; adequate MEG data were obtained from 3 of the patients. Equivalent current dipoles for MRFs were estimated with the following parameters: goodness of fit (> 75%), confidence volume (< 6000 mm3), and the duration of dipole (> 10 msec). In addition to the single dipole analysis, Minimum Current Estimates were applied for source estimation since neural activities for stroke patients were observed at the motor cortex of the contralateral side as well as other areas of the brain. Contralateral motor cortex was activated for the normal subjects at 50 ms prior to the force onset, whereas ipsilateral motor cortex was activated for some stroke patients and patients' dipole moments differed not only in their locations but also in their latencies, ranging from -150 to 50 ms to the force onset. The results were in agreement with the findings by PET and fMRI studies; therefore, it was implied that the compensating motor functions were shifted to neighboring areas of the brain due to the recovering motor function after stroke.

Adult↗
PubMed2004

Aberrant dynamics of histone deacetylation at the thyrotropin-releasing hormone gene in resistance to thyroid hormone.

Histone acetylation status influences transcriptional activity, and the mechanism of negative gene regulation by thyroid hormone remains unclear, although its impairment by a mutant thyroid hormone receptor (TR) is critical for resistance to thyroid hormone (RTH). We found a novel RTH mutant, F455S, that exhibited impaired repression of the TRH gene and had a strong dominant-negative effect on the gene. F455S strongly interacted with nuclear receptor corepressor (NCoR) and was hard to dissociate from it. To analyze the dynamics of histone acetylation status in vivo, we established cell lines stably expressing the TRH promoter and wild-type or F455S TR. Treatment with a histone deacetylase (HDAC) inhibitor completely abolished the repression of the gene by T3. The histones H3 and H4 at the TRH promoter were acetylated, and addition of T3 caused recruitment of HDACs 2 and 3 within 15 min, resulting in a transient deacetylation of the histone tails. TR and NCoR were located on the promoter, and T3 caused NCoR dissociation and steroid receptor coactivator-1 recruitment. In the presence of F455S, the histones were hyperacetylated, and HDAC recruitment and histone deacetylation were significantly impaired. This is the first report demonstrating the direct involvement of aberrant dynamics of chromatin modification in RTH.

Acetylation↗
PubMed2004

Phase I/II study of cisplatin combined with weekly paclitaxel in patients with advanced non-small-cell lung cancer.

To determine the maximum-tolerated dose (MTD) and the recommended dose (RD) of paclitaxel administered weekly with a fixed dose of cisplatin, and to assess the toxicity and activity of this combination, we conducted a phase I/II trial in patients with advanced non-small-cell lung cancer (NSCLC). In this study, patients with stage IIIB/IV NSCLC were eligible. Paclitaxel, at a starting dose of 40 mg x m(-2) week(-1) on days 1, 8, and 15, was combined with a fixed dose of cisplatin 80 mg x m(-2) on day 1. Chemotherapy was given in a 4-week cycle. In this phase I/II study, 38 patients were enrolled. Dose-limiting toxicities (DLT) were neutropenia, fatigue, and omission of treatment due to leucopenia, thrombocytopenia, or febrile neutropenia. The MTD and RD were estimated to be 70 mg x m(-2). Of the 37 assessable patients, 23 had a partial response and one had a complete response. Overall response rate was 62.1% (95% confidence interval (CI): 46.5-77.7%). The progression-free survival, the median survival time, and the 1-year survival rate were 5.5 months, 13.7 months, and 56.9%, respectively. This regimen is tolerable and very active against advanced NSCLC, and its efficacy should be confirmed in a phase III study.

Adult↗
PubMed2004

Energetic costs of bipedal and quadrupedal walking in Japanese macaques.

We investigated the energetic costs of quadrupedal and bipedal walking in two Japanese macaques. The subjects were engaged in traditional bipedal performance for years, and are extremely adept bipeds. The experiment was conducted in an airtight chamber with a gas analyzer. The subjects walked quadrupedally and bipedally at fixed velocities (<5 km/hr) on a treadmill in the chamber for 2.5-6 min. We estimated energy consumption from carbon dioxide (CO2) production. While walking bipedally, energetic expenditure increased by 30% relative to quadrupedalism in one subject, and by 20% in another younger subject. Energetic costs increased linearly with velocity in quadrupedalism and bipedalism, with bipedal/quadrupedal ratios remaining almost constant. Our experiments were relatively short in duration, and thus the observed locomotor costs may include presteady-state high values. However, there was no difference in experimental duration between bipedal and quadrupedal trials. Thus, the issue of steady state cannot cancel the difference in energetic costs. Furthermore, we observed that switching of locomotor mode (quadrupedalism to bipedalism) during a session resulted in a significant increase of CO2 production. Taylor and Rowntree ([1973] Science 179:186-187) noted that the energetic costs for bipedal and quadrupedal walking were the same in chimpanzees and capuchin monkeys. Although the reason for this inconsistency is not clear, species-specific differences should be considered regarding bipedal locomotor energetics among nonhuman primates. Extra costs for bipedalism may not be great in these macaques. Indeed, it is known that suspensory locomotion in Ateles consumes 1.3-1.4 times as much energy relative to quadrupedal progression. This excess ratio surpasses the bipedal/quadrupedal energetic ratios in these macaques.

Animals↗
PubMed2004

Neurogenesis in olfactory bulb identified by retroviral labeling in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated adult mice.

Neurogenesis occurs during development and in the normal adult brain. Recent studies identified areas exhibiting postlesional selective neurogenesis and neuronal repair. In the olfactory bulb (OB), one of the most studied regions of the brain for neurogenesis, seizures and strong odor exposure are known to enhance neurogenesis. Here, we report enhanced neurogenesis in OB after dopaminergic neuronal loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective toxin for dopaminergic neurons. The neurogenesis has been previously confirmed mainly by the uptake of 5-bromodeoxyuridine (BrdU), a marker of proliferating cells, but methodological problems related to BrdU labeling might result in inaccurate findings with respect to specificity, toxicity and incorporation into normal/lesioned brain. For a better identification of neurogenesis, we used a retroviral vector. First, we investigated the population dynamics of newly formed neurons in different regions of OB including the glomerular layer, the most superficial layer of OB. Quantification of neurogenesis in OB revealed by our retroviral vector was substantially similar to that by BrdU-based method. One week after MPTP application and dopaminergic neuronal loss in OB, neurogenesis of dopaminergic neurons in OB increased by three-fold, but no such process was noted in non-dopaminergic neurons. Our results indicate selective dopaminergic neurogenesis in OB in response to neuronal damage/loss.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2004

Effect of memantine on the levels of glial cells, neuropeptides, and peptide-degrading enzymes in rat brain regions of ibotenic acid-treated alzheimer's disease model.

It has been implicated that glia activation plays a critical role in the progression of Alzheimer's disease (AD). However, the precise mechanism of glia activation is not clearly understood yet. In our present studies, we confirmed our previous results where change the levels of neuropeptides and peptidases in ibotenic acid (IBO) infusion into the rat nucleus basalis magnocellularis, an animal model of AD. Furthermore, we extended our study to investigate a possible protection effect of co-administration on the changes of neuropeptides, and neuronal and glial cells in IBO-infused rat brain by memantine treatment. The levels of substance P and somatostatin were decreased in the striatum and frontal cortex 1 week after IBO infusion, and recovered to the control level by memantine treatment, indicating the involvement of neuropeptides in AD pathology. Furthermore, the immunohistochemical and enzymatic studies of GFAP and CD 11b, and peptidylarginine deiminase, markers of glia, in the striatum and frontal cortex showed the increase in IBO-treated rat brain as compared with controls, while co-administration of memantine and IBO no increase of astrocytes and microglia activation was observed. The present biochemical and immunohistochemical results suggest that glia activation might play an important role to the pathology of AD, and correlate with the changes of neuropeptide levels in AD brain that is recovered by memantine treatment.

Alzheimer Disease↗
PubMed2004

Induction of inducible nitric oxide synthase in hepatocytes isolated from rats with ischemia-reperfusion injury.

BACKGROUND: Recent evidence indicates that nitric oxide (NO) has a crucial role in hepatic ischemia-reperfusion (I/R) injury. However, little is known about how I/R influences the gene expression of inducible nitric oxide synthase (iNOS) in hepatocytes. Under inflammatory conditions, we compared the induction of iNOS in hepatocytes isolated from normal and I/R-treated rats. METHODS: Hepatocytes were isolated using the collagenase perfusion method from rats treated with I/R (30-minute ischemia of middle and left lobes, followed by 3-hour reperfusion) or sham operation (control): Primary cultures of rat hepatocytes were incubated with an inflammatory cytokine, interleukin-1beta (IL-1beta), to compare the iNOS induction/NO production between the 2 groups. RESULTS: Both control and I/R groups had no production of nitrite (a stable metabolite of NO) in the absence of IL-1beta. In the control group, IL-1beta stimulated dose- and time-dependent production of NO. The I/R group showed more than 2-fold increased levels of NO production. Western and Northern blot analyses revealed that the I/R group also showed increased levels of iNOS protein and its messenger RNA. CONCLUSION: These results suggest that I/R directly affects the inducibility of the iNOS gene in hepatocytes by IL-1beta. Increased NO may be associated with protective or toxic effects in hepatic I/R injury.

Animals↗