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Biomedical subjects

A Hayashi

Publications and source records attributed to A Hayashi.

At least 55 records · Page 3Linked to original sources
PubMed2000

In vivo gene gun-mediated DNA delivery into rodent brain tissue.

Various types of gene transfer into live tissues have been tried. However, in vivo gene transfer into brain tissue or neuronal cells without virus vector has required a great effort. Particle-mediated gene transfer into live brain tissue was thought to be impossible because of its fragility and the mechanical problem of a previous type of gene gun. In addition, particle-mediated DNA transfer into monolayer-cultured cells without mechanical damage has been difficult. We successfully transferred DNA into rodent live brain tissue and also into monolayer-cultured cells without mechanical damage by using a new type of gene gun and also confirmed gene expression in the brain. This new method represents another variation of gene transfer into the brain.

Animals↗
PubMed2000

Cross-cultural traits for personality of patients with Parkinson's disease in Japan.

Recent studies suggest that Parkinson's disease (PD) is associated with particular personality traits. Using Cloningers's Tridimensional Personality Questionnaire (TPQ), Menza and colleagues [1993: Neurology 43:505-508] reported a possible association between PD and a reduced score in the novelty seeking (NS) dimension of the TPQ. We sought to determine whether this association, which was found in a study conducted in the United States, could also be found among Japanese PD patients. We performed personality assessments of 67 Japanese PD patients, using the TPQ test. The results suggest that Japanese PD patients have significantly lower scores in the NS dimension of the TPQ, as well as significantly higher harm avoidance (HA) scores, compared with matched control subjects. Furthermore, the PD patients undergoing treatment for depression using antidepressant drugs scored significantly higher in the HA dimension than PD patients who did not receive antidepressant drug treatment. Our results suggest that the high HA score, and the low NS score in the TPQ test observed in patients with PD, is a cross-cultural phenomenon, although the influence of depression, long-term treatment, and premorbid gene/environmental interactions may also affect these personality traits. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:1-3, 2000.

Aged↗
PubMed2000

The visual performance and metamorphopsia of patients with macular holes.

BACKGROUND: Most patients attain better visual acuity with the elimination of metamorphopsia after successful closure of a macular hole (MH) by vitrectomy. OBJECTIVE: To determine the presurgical visual function of eyes with an MH. METHODS: We examined 54 eyes of 51 patients with an idiopathic MH using the Amsler chart. We evaluated the types of subjective metamorphopsia and compared them with the clinical factors associated with MHs. In a prospective study, we performed a montage test on a separate group of 16 patients with unilateral idiopathic MHs. The patients were asked to choose, while viewing with their better eye, the computer-modified picture that best matched the unmodified image seen by the eye with the MH. RESULTS: From the results of the Amsler chart test, we divided the subjective changes into 2 types of metamorphopsia; of the 54 eyes, pincushion distortion (bowed toward the center) was found in 33 (61%), and unpatterned distortion (no specific pattern) was found in 21 (39%). Pincushion distortion was significantly associated with an MH of shorter duration (< or =6 months) (P = .03) and an early stage (stage 2) of MH formation (P = .02). A scotoma was hard to detect, and patients had difficulty describing their scotomata and distortions. In the montage test, patients with early MHs chose portraits modified with a pincushion type of distortion. CONCLUSIONS: We found concentric pincushion metamorphopsia without subjective scotomata, which we suggest arises from an eccentric displacement of the photoreceptors. This accounts for the main characteristic of the visual performance of patients with idiopathic MHs.

Aged↗
PubMed2000

Fusogenic liposomes efficiently deliver exogenous antigen through the cytoplasm into the MHC class I processing pathway.

Exogenous soluble proteins enter the endosomal pathway by endocytosis and are presented in association with MHC class II rather than class I. In contrast, the delivery of exogenous protein antigens (Ag) into the cytosol generates MHC class I-restricted cytotoxic T lymphocytes (CTL) responses. Although several immunization approaches, such as the utilization of liposomes, have induced the in vivo priming of MHC class I-restricted CTL responses to protein Ag, it remains unclear whether this priming results from the direct delivery of protein Ag to the cytosol. Here we report that fusogenic liposomes (FL), which are prepared by fusing simple liposomes with Sendai virus particles, can deliver the encapsulated soluble protein directly into the cytosol of cells cultured concurrently and introduce it into the conventional MHC class I Ag presentation pathway. Moreover, a single immunization with ovalbumin (OVA) encapsulated in FL but not in simple liposomes results in the potent priming of OVA-specific CTL. Thus, FL function as an efficient tool for the delivery of CTL vaccines.

Animals↗
PubMed2000

Innate immune therapy for cancer. Screen for molecules capable of activating the innate immune system.

Tumor cells usually express antigens which are distinguishable from normal "self" antigens and are thereby recognized by the host immune system. However, the host immune system barely responds to tumors in patients. Supplementation with adjuvant (such as BCG-CWS) in patients with cancer contributes to regression of intrinsically growing cancer. The adjuvant targets antigen-presenting cells, i.e. innate immunity, but not lymphocytes, and promotes up-regulation of MHC, co-stimulators and initial cytokines in antigen-presenting cells. We hypothesized that the role of the adjuvant is to provide conditions suitable for antigen-presentation where antigens are available and the lack of adjuvant-induced priming of antigen-presenting cells results in unresponsiveness to tumor antigens. Here, we report innate immune therapy applicable to cancer patients by supplementation with adjuvants for induction of potent immune responses against tumors.

Humans↗
PubMed2000

Relationship between cancer cell proliferation and thallium-201 uptake in lung cancer.

UNLABELLED: Although thallium-201 (201Tl) uptake is related to perfusion in many normal tissues, the biologic rationale for 201Tl uptake in tumors is uncertain. To determine if tumor uptake is related to cell proliferation, we correlated the relative retention of 201Tl in lung tumors with expression of Ki-67, an indicator of cell proliferation. METHODS: Sixty patients with lung tumors, included small cell carcinoma (n = 8) and non-small cell carcinoma (n = 52), underwent 201Tl single photon emission computed tomography (SPECT) imaging. The 201Tl lesion uptake was determined on early and delayed images and the radiotracer retention index (RI) was calculated. Tumor specimens were obtained at surgery or bronchoscopy. The cell proliferation ratio was estimated with MIB-1, a monoclonal antibody that recognized the nuclear antigen Ki-67. RESULTS: The average 201Tl index was 2.13+/-0.61 (early) and 2.46+/-0.83 (delayed). The average RI was 17.44+/-35.01. Overall, the 201Tl index (delayed) and the cancer cell proliferation were correlated (r = 0.70, p < 0.0001). Of interest, there was a significant correlation (r = 0.872, p < 0.0005) between the 201Tl index on delayed images and the cell proliferation ratio in patients with small cell but not non-small cell lung carcinoma. The 201Tl index (delayed) was significantly higher (p < 0.0001) in patients with small cell lung carcinoma than in patients with non-small cell lung carcinoma. CONCLUSION: 201Tl imaging appears to be useful for evaluating patients with small cell lung carcinoma but not non-small lung carcinoma, and is correlated with the monoclonal antibody MIB-1, a marker of cell proliferation.

Adult↗
PubMed2000

An experimental study of atrial natriuretic peptide levels and the effect of inhaled nitric oxide after pneumonectomy.

The aim of this study was to investigate the changes in atrial natriuretic peptide (ANP) levels and lung cyclic guanosine 3',5'-monophosphate (cGMP) concentrations caused by pneumonectomy (Pn), and the effect of inhaled nitric oxide (NO) after Pn in a canine model. The mean pulmonary arterial pressure (PAP) and plasma ANP levels were measured over 180 min in two groups of dogs, one subjected to 60 min of 5 ppm NO inhalation (Pn + NO group, n = 5) and one subjected to 180 min without NO inhalation (Pn group, n = 5). The ANP and cGMP levels in the lung were also measured before and after Pn. Both the PAP and ANP levels increased significantly. Inhaled NO rapidly reduced the PAP and plasma ANP to levels similar to those before Pn. The lung ANP level was significantly increased after Pn, but inhaled NO reduced it to a level similar to that before Pn. The lung cGMP level, which was significantly decreased after Pn, was significantly increased by NO inhalation. These results indicate that NO administration may be effective for preventing post-Pn pulmonary hypertension, although an elevation in ANP does not reduce the PAP.

Animals↗
PubMed2000

Optical coherence tomography patterns of choroidal osteoma.

PURPOSE: To determine the optical coherence tomographic images that are commonly observed in eyes with choroidal osteoma (choroidal ossification). METHODS: Three patients with choroidal osteoma were examined by optical coherence tomography. RESULTS: We found two optical coherence tomographic patterns in the eyes with choroidal osteoma. First, multiple tracks of high refractivity were present posterior to the tumor lesion. Second, thick and irregular plate-like, high-signal intensity areas were present in the choroid in the region of the tumor. CONCLUSIONS: Optical coherence tomography can be useful in the diagnosis of choroidal osteoma.

Adult↗
PubMed2000

Amsler grid examination and optical coherence tomography of a macular hole caused by accidental Nd:YAG laser injury.

PURPOSE: To compare a macular hole from accidental Nd:YAG laser injury with idiopathic macular holes. METHODS: Case report. In a 24-year-old man with accidental Nd:YAG laser injury, right eye, Amsler grid testing and optical coherence tomography were performed. RESULTS: Nd:YAG laser injury was responsible for a macular hole about 700 microm in diameter. The visual acuity was 20/100. Amsler grid testing displayed a central scotoma with no surrounding distortion. Optical coherence tomography showed a defect in all retinal layers at the macula. CONCLUSION: The scotoma caused by Nd:YAG laser injury is not surrounded by distortion; the hole is produced by the defect of all retinal layers. In contrast, idiopathic macular holes generally produce a pincushion pattern on Amsler grid testing and have no tissue loss.

Accidents, Occupational↗
PubMed2000

Comparison of visual function after foveal translocation with 360 degrees retinotomy and with scleral shortening in a patient with bilateral myopic neovascular maculopathy.

PURPOSE: To compare the visual outcome after foveal translocation by scleral shortening and that after 360 degrees retinotomy with extraocular muscle surgery in a patient with bilateral myopic neovascular maculopathy. METHODS: Case report. RESULTS: A 52-year-old woman with bilateral myopic neovascular maculopathy underwent foveal translocation with scleral shortening in the left eye, and visual acuity improved from 20/70 to 20/30. However, choroidal neovascularization recurred, and the final visual acuity was 20/40 after excision of the choroidal neovascularization. Foveal translocation with 360 degrees retinotomy was performed on the right eye, and visual acuity improved from 20/150 to 20/30. The critical print size was better, and the retinal sensitive area was larger in the right eye. CONCLUSION: The better reading ability shown by foveal translocation by a 360 degrees retinotomy compared with scleral shortening may stem from a larger retinal sensitive area obtained by this method.

Choroidal Neovascularization↗
PubMed2000

Inhibition of experimental choroidal neovascularization by overexpression of tissue inhibitor of metalloproteinases-3 in retinal pigment epithelium cells.

PURPOSE: To evaluate the feasibility of introducing exogenous tissue inhibitor of metalloproteinases-3 gene into the rat retinal pigment epithelium using hemagglutinating virus of Japan liposomes and to assess the effect of tissue inhibitor of metalloproteinases-3 overexpression in retinal pigment epithelium cells on the formation of experimental choroidal neovascularization. METHODS: Hemagglutinating virus of Japan liposomes containing hemagglutin epitope-tagged tissue inhibitor of metalloproteinases-3 gene were injected into the subretinal space in rat eyes. Localization of oligonucleotides was evaluated by fluorescence microscopy. Exogenous tissue inhibitor of metalloproteinases-3 mRNA expression was assessed by reverse transcribed polymerase chain reaction. Exogenous tissue inhibitor of metalloproteinases-3 protein expression was visualized by immunostaining with monoclonal antibody 12CA5 against the hemagglutin epitope. Three days after transfection of tissue inhibitor of metalloproteinases-3 gene into retinal pigment epithelium cells, intense laser photocoagulation was performed and the incidence of choroidal neovascularization was assessed by fluorescein fundus angiography. RESULTS: Exogenous tissue inhibitor of metalloproteinases-3 mRNA expression in the choroid and retina was detected on day 3. The efficiency of tissue inhibitor of metalloproteinases-3 gene transfection into retinal pigment epithelium cells was greatest on day 7 and decreased gradually thereafter. The incidence of choroidal neovascularization in tissue inhibitor of metalloproteinases-3 gene-transfected eyes was markedly decreased compared with controls. CONCLUSIONS: This study shows that tissue inhibitor of metalloproteinases-3 gene can be transferred into rat retinal pigment epithelium using the hemagglutinating virus of Japan-liposome method and that tissue inhibitor of metalloproteinases-3 gene overexpression can inhibit development of experimental choroidal neovascularization. This method may represent a future treatment modality for human macular degeneration associated with choroidal neovascularization.

Animals↗
PubMed2000

A preoperative alternating chemotherapy and radiotherapy program for patients with stage IIIA (N2) non-small cell lung cancer.

The objective of the present study was to evaluate the feasibility and toxicity of a preoperative alternating chemotherapy and radiotherapy program followed by surgery in stage IIIA non-small cell lung cancer (NSCLC). The tumor response, resection rate, tumor/lymph node downstaging, and survival were also evaluated. The positive predictive value (PPV) in the diagnosis of mediastinal lymph node metastasis was 81% using conventional magnetic resonance imaging (MRI) with short inversion-time inversion recovery (STIR) technique (STIR-MRI) on our criteria. Eligible patients had clinical N2 lesions (stage IIIA) and a World Health Organization (WHO) performance status of 0-2. The treatment program consisted of two courses of preoperative cisplatin, vindesine, and ifosfamide; alternating with radiotherapy, including two courses of 20 Gy radiation. Surgery was performed within 4 weeks after the treatment. Twenty-two patients with stage IIIA (N2) NSCLC (20 men and two women, age 35-71 years) were enrolled into the study. Hematologic and other toxicities were within an acceptable range. Surgery was not indicated for two patients because of distant metastasis; one patient with renal dysfunction and one with pancytopenia during this treatment underwent surgery subsequently. The clinical response rate was 50% (partial response in 11/22). Definitive surgery was indicated for 18 patients resulting in 17 patients with complete resection and one exploratory thoracotomy. A pathologic complete response of the primary tumor occurred in 41% of the patients (seven of 17; without residual tumor), whereas 58% (ten of 17) were pathologic N0. The median survival was 33 months with an actuarial 4-year survival rate of 33% in 17 patients with complete resection and 30 months with 28% 4-year survival rate in all entered patients. A randomized phase-III study using this approach for stage IIIA (clinical N-2 disease) is warranted.

Adult↗
PubMed2000

Autoimmunity to gephyrin in Stiff-Man syndrome.

Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by chronic rigidity, spasms, and autoimmunity directed against synaptic antigens, most often the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). In a subset of cases, SMS has an autoimmune paraneoplastic origin. We report here the identification of high-titer autoantibodies directed against gephyrin in a patient with clinical features of SMS and mediastinal cancer. Gephyrin is a cytosolic protein selectively concentrated at the postsynaptic membrane of inhibitory synapses, where it is associated with GABA(A) and glycine receptors. Our findings provide new evidence for a close link between autoimmunity directed against components of inhibitory synapses and neurological conditions characterized by chronic rigidity and spasms.

Animals↗
PubMed2000

Glycosylated human interleukin-1alpha, neoglyco IL-1alpha, coupled with N-acetylneuraminic acid exhibits selective activities in vivo and altered tissue distribution.

In order to study the effect of glycosylation on its biological activities and to develop IL-1 with less deleterious effects, N-acetylneuraminic acid (NeuAc) with C9 spacer was chemically coupled to human recombinant IL-1alpha. NeuAc-coupled IL-1alpha (NeuAc-IL-1alpha) exhibited reduced activities in vitro and receptor-binding affinities by about ten times compared to IL-1alpha. In this study, we examined a variety of IL-1 activities in vivo. NeuAc-IL-1alpha exhibited a marked reduction in the activity to up-regulate serum IL-6, moderate reduction in the activities to up-regulate serum amyloid A and NOx. However, it exhibited comparable activities as IL-1alpha to down-regulate serum glucose and to improve the recovery of peripheral white blood cells from myelosuppression in 5-fluorouracil-treated mice. In addition, tissue level of NeuAc-IL-1alpha was high compared to IL-1alpha. These results indicate that coupling with NeuAc enabled us to develop neo-IL-1 with selective activities in vivo and enhanced tissue level.

Animals↗
PubMed2000

Regulatory effect of interleukin-4 and interleukin-13 on colon cancer cell adhesion.

To assess the role of interleukin-4 (IL-4) and interleukin-13 (IL-13) in colon cancer cell-cell adhesion, we investigated the effect of both cytokines in human colon cancer cell line, colo205 cell-cell adhesion. IL-4 receptor was expressed on the cell surface of colo205, and recombinant IL-4 inhibited colo205 cell-cell adhesion in a dose-dependent fashion without inhibiting cell proliferation. Flow cytometric analysis revealed that monoclonal antibodies (mAbs) directed against E-cadherin and carcinoembryonic antigen (CEA) inhibited colo205 cell-cell adhesion and IL-4 significantly inhibited the expression of E-cadherin and CEA. IL-13 also inhibited colo205 cell-cell adhesion. These results indicated that IL-4 and IL-13 inhibited colon cancer cell-cell adhesion by down-regulation of E-cadherin and CEA molecules. We then investigated the expression of both cytokines from freshly isolated colon cancer tumour-infiltrating lymphocytes (TILs). With reverse transcription-polymerase chain reaction and flow cytometric analysis, we demonstrated that colon TILs expressed IL-4 and IL-13 mRNA and protein. These results suggest that Th 2 type cytokines IL-4 and IL-13 locally-produced from TILs may regulate colon cancer adhesion by down-regulation of adhesion molecules.

Cadherins↗