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Biomedical subjects

Y Ando

Publications and source records attributed to Y Ando.

At least 271 records · Page 15Linked to original sources

Unexpected correlation in the sensitivity of 19 herpes simplex virus strains to types I and II interferons.

We compared the sensitivity of 19 herpes simplex virus (HSV) strains to type I (IFN-alpha and IFN-beta) and type II (IFN-gamma) human interferons in cultures of human retinal epithelial (K-1034) and lung (HEL) cells. Their sensitivities proved to be well correlated, even though type I and type II IFN have been reported to have different antiviral actions. The correlation was not because IFN-gamma stimulated the formation of IFN-beta, for an antibody that neutralized IFN-beta did not reduce its inhibitory effects. Our results show that each HSV strain has a characteristic and similar sensitivity to type I and type II IFN and suggest some common pathway in the mechanism of their antiviral actions.

Cells, Cultured↗

Difference in affinity for DNA between HMG proteins 1 and 2 determined by surface plasmon resonance measurements.

High mobility group (HMG) proteins 1 and 2 contain two similar but non-identical repeats of DNA-binding domains and an acidic C-terminal. The proposed functions of HMG proteins 1 and 2 imply a probable difference in their DNA-binding abilities. The primary studies by gel retardation assay showed that HMG2 has higher affinity than HMG1 for supercoiled and linear DNA. The DNA-binding of HMG2 appeared strong enough to allow exchange with HMG1 molecule already bound to DNA, while the DNA-binding region of HMG1 showed higher affinity than that of HMG2. In order to compare more quantitatively the affinities, surface plasmon resonance (SPR) measurements using a BIAcore instrument were conducted. The kinetic data indicated that the Kd for the complex of HMG2 with DNA is smaller than that of HMG1, in contrast to the situation for the DNA-binding region of these proteins. The sequence between the second DNA-binding domain and the acidic C-terminal of HMG proteins is required for tight DNA-binding. Also, the acidic C-terminal strongly modulates the DNA-binding ability of each protein. The usefulness of SPR measurement for quantitative analysis of affinity and regions involved in DNA-binding under conditions nearly identical to those in solution is discussed.

Animals↗

Arginine vasopressin inhibits interleukin-1 beta-stimulated nitric oxide and cyclic guanosine monophosphate production via the V1 receptor in cultured rat vascular smooth muscle cells.

BACKGROUND: It has been reported that various vasoactive substance modulate cytokine stimulated nitric oxide (NO) production in many cell types. OBJECTIVE: To examine the effects of arginine vasopressin (AVP) on the production of NO and cyclic GMP (cGMP), and on inducible nitric oxide synthase (INOS) in cultured rat vascular smooth muscle cells (VSMC). DESIGN: Because VSMC possess the V1 receptor which clauses vascular contraction and respond to various cytokines for producing NO, we used rat VSMC and selected interleukin-1 beta (IL-1 beta) as a potent stimulator of NO production among various cytokines. We also measured cGMP production, which is the final mediator of NO-induced vascular relaxation, in order to evaluate the physiologic meaning of the present study. METHODS: VSMC were incubated with test agents for 24 h except for a time-course study. Nitrite as a stable end product of NO was measured in the medium. Intracellular cGMP contents were assayed by enzyme immunoassay. INOS messenger RNA expression was analyzed by Northern blotting. RESULTS: AVP inhibited IL-1 beta-induced nitrite production in a dose- and time-dependent manner with concomitant changes in intracellular cGMP contents. On the other hand, AVP did not affect nitrite and cGMP production in the absence of IL-1 beta. Inhibition of nitrite and cGMP production by AVP was reversed by administration of the specific V1 receptor antagonist [1-(beta-mercapto-beta,beta- cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine] -Arg8-vasopressin) but not by the oxytocin (OXT) receptor antagonist [d(CH2(5)), TyrMe2, Orn8]-Vasotocin. Administration of the V1 receptor antagonist or OXT receptor antagonist alone did not affect IL-1 beta-stimulated nitrite and cGMP production. Although administration of AVP inhibited IL-1 beta-induced INOS messenger RNA expression, administration of the V1 receptor antagonist but not of the OXT receptor antagonist reversed this inhibition. CONCLUSION: It is suggested that AVP inhibits IL-1 beta-induced NO and cGMP production via the V1 receptor but not via the OXT receptor in VSMC. AVP can cause vascular contraction not only through direct action but also through indirect action by inhibiting NO production under some inflammatory conditions.

Animals↗

Contrast mapping and evaluation for electronic X-ray images on CRT display monitor.

Simple chest X rays on film are the most common type of image in medical diagnosis. However, amongst the various types of medical X-ray images, they require the highest level of display quality due to the fact that the body structures they capture on film have varying degrees of permeability to X rays. Conventional high-definition digital display technology has not always been able to match the quality of such film images. This has been a major impediment against progress toward the complete digitization of simple chest X rays. The intent of this paper is to examine that, when applied to medical diagnosis of chest X rays, super-high-definition (SHD) images (digital images with resolution exceeding that of HDTV) are capable of producing a level of quality of diagnostic accuracy on a par with conventional film images. We will start out by seeking out the overall transmission characteristics of a system that uses digital radiography and a film digitizer to digitize images. We will then derive gray-scale transform characteristics based on the luminance linear method for approximating, as closely as possible on a CRT, film images on a light box that have wide dynamic range and high luminance. Finally, we will present the results of image evaluation experiments using high-definition CRT monitors. These results indicate that conventional film images and those on super-high-definition CRT monitors have nearly the same quality. They will also show that the contrast mapping selected by radiologists and theoretical luminance linear characteristics were almost the same except in low-luminance regions. We will also discuss radiologists' comments on CRT monitors after they participated in the evaluation experiment.

Data Display↗

Nitric oxide synthase activity in human lung cancer.

Nitric oxide synthases (NOS) exist in human tumor cell lines and solid tumor tissues, and it has been suggested that NO may play important roles in growth, progression or metastasis of tumors. We investigated the activity and distribution of NOS in a series of human cancer and normal lung tissues. Seventy-two primary lung cancer samples (44 cases of adenocarcinoma, 18 of squamous cell carcinoma, 4 of large cell carcinoma, 2 of small cell carcinoma, 2 of adenosquamous carcinoma, and 2 of carcinoids) and corresponding normal lung samples were obtained from surgically treated patients. In normal lung tissues, little NOS activity was observed with no correlation between the patient's age and NOS activity. The total NOS activities in lung adenocarcinoma samples were significantly higher than those in other types of lung cancers of normal lung samples (P < 0.05). Analysis by tumor grade of the adenocarcinoma samples revealed no significant difference of NOS activity between grades. TNM classification showed that, although T stage did not correlate with NOS activity, cancer tissues from patients with N2 disease tended to have lower activity than those from patients with NO or N1 disease. Immunohistochemical studies revealed that the intensity of NOS immunoreactivity correlated with NOS activity. These results suggest that NO may play an important role in the metabolism and behavior of lung cancers, especially adenocarcinoma.

Adult↗

Pharmacokinetic study of carboplatin given on a 5-day intravenous schedule.

We investigated whether carboplatin pharmacokinetics is altered when the drug is delivered daily over 5 days, compared to a single-day infusion. Carboplatin was infused in 11 patients with lung cancer, who were randomly assigned to 2 groups. In the first group, the agent was administered on a conventional single-day schedule in the first course and then on a 5-day schedule in the second course. In the second group, the order was reversed (crossover design). The dose was calculated using Calvert's formula with 24 h creatinine clearance (Ccr, ml/min) as a substitute for glomerular filtration rate (GFR): carboplatin (mg) = AUCx(Ccr+25), where AUC denotes the area under the concentration versus time curve (mg ml-1 min). No difference of carboplatin clearance between the single-day and 5-day schedule was observed (94.8 +/- 19.9 versus 96.1 +/- 29.9 ml/min, P = 0.818, paired t test). The formula systematically overestimated the carboplatin clearance: the ratio of estimated clearance/ observed clearance ranged from 1.01 to 1.58 (median 1.28; 95% confidence interval, 1.18 to 1.39). We concluded that the individual dosing strategy based on renal function can be applied with a 5-day schedule as well as a single-day schedule. Carboplatin is overdosed when Ccr is substituted for GFR in Calvert's formula.

Aged↗

Cytotoxicity of trimetrexate against antifolate-resistant human T-cell leukemia cell lines developed in oxidized or reduced folate.

Cytotoxicity of trimetrexate (TMQ), a lipophilic dihydrofolate reductase inhibitor, was examined in antifolate-resistant human T-cell leukemia cell lines developed in oxidized or reduced folate. An approximately 60-fold methotrexate (MTX)-resistant subline was developed in oxidized folate (pteroylglutamic acid: PGA) (CCRF-CEM/MTX60-PGA) from human T-cell leukemia cell line CCRF-CEM; this line exhibited impaired membrane transport of the drug. Further enhancement of MTX resistance resulted in selection of an approximately 5000-fold MTX-resistant subline (CCRF-CEM/ MTX5000-PGA), which showed increased dihydrofolate reductase activity due to gene amplification in addition to further impairment of MTX transport. An approximately 140-fold MTX-resistant subline, and then a 1500-fold MTX-resistant subline were developed in reduced folate (10 nM leucovorin) (CCRF-CEM/MTX140-LV and CCRF-CEM/MTX1500-LV); they exhibited increased dihydrofolate reductase due to gene amplification accompanied by increased intracellular drug accumulation of MTX. While CCRF-CEM/MTX140-LV and CCRF-CEM/MTX1500-LV cells showed cross-resistance to TMQ, CCRF-CEM/MTX60-PGA and CCRF-CEM/MTX5000-PGA cells were at least as sensitive to TMQ as the parent cells. TMQ was more potent against approximately 200-fold N10-propargyl-5,8-dideazafolic-acid (CB3717)-resistant human T-cell leukemia MOLT-3 sublines developed in PGA (MOLT-3/CB3717(200)-PGA) or leucovorin (MOLT-3/CB3717(200)-LV), as compared to the parent cells; MOLT-3/CB3717(200)-PGA and MOLT-3/CB3717(200)-LV cells were resistant to CB3717 by virtue of impaired transport, only the former possessing gene amplification of thymidylate synthase. The cytotoxicity of TMQ in both MOLT-3/CB3717(200)-PGA and MOLT-3/CB3717(200)-LV cells was reduced by addition of leucovorin in a dose-dependent manner, suggesting intracellular folate deficiency as a cause of TMQ sensitivity. These results demonstrate that TMQ overcomes transport-impaired antifolate resistance, irrespective of gene amplification of dihydrofolate reductase or thymidylate synthase. Types of folate used during the development of antifolate resistance seem to be important in relation to the mechanism of TMQ responsiveness as well as that of antifolate resistance.

Antimetabolites, Antineoplastic↗

Late onset type I familial amyloidotic polyneuropathy: presentation of three autopsy cases in comparison with 19 autopsy cases of the ordinary type.

Clinicopathological features of three autopsy cases of extremely rare late onset type I familial amyloidotic polyneuropathy were presented and compared with 19 autopsy cases of the ordinary type. In the late onset cases, the ages at onset and at death were 27.5 and 24.5 years older, respectively, compared with the ordinary type. Also, duration of the total clinical course from onset to death was 3.7 years less than in the late onset cases. The degree of amyloid deposition was more marked in the heart of the late onset cases, causing prominent cardiac hypertrophy. It was also marked in the kidneys or thyroid of two cases, but slight to moderate in the peripheral or autonomic nervous tissues in all cases. Immunohistochemical investigation demonstrated the presence of transthyretin (TTR) as an amyloid precursor protein and of serum amyloid P-component in amyloid deposits in various organs and tissues of the late onset type. These findings, as well as serum levels of variant TTR, were similar to those of the ordinary type. These results suggest that there are some factors other than the amyloid precursor protein that effect the degree of amyloid deposition.

Adolescent↗

Incidence of delayed onset infection after trabeculectomy with adjunctive mitomycin C or 5-fluorouracil treatment.

AIMS/BACKGROUND: The introduction of the adjunctive use of antiproliferatives to trabeculectomy has greatly improved the success rate of this operation. Trabeculectomy with antiproliferative treatment, however, is usually associated with a cystic and thin walled filtering bleb, which may be more susceptible to infection. The objective of this study was to evaluate the incidence, clinical findings, and risk factors of delayed onset, bleb related infection after trabeculectomy with adjunctive mitomycin C (MMC) or 5-fluorouracil (5-FU) treatment. METHODS: The records of 632 glaucoma patients who underwent 966 trabeculectomies, with and without the use of adjunctive MMC or 5-FU treatment, between January 1985 and February 1995 were analysed. The mean follow up period was 3.5 (2.4) years (range 0.1 to 11.2 years). The mean patient age was 54.8 (18.8) years (range 0 to 88 years). RESULTS: Bleb related infection occurred in one of 76 trabeculectomies that did not receive antiproliferatives (1.3%), three of 228 treated with 5-FU (1.3%) trabeculectomies, and seven of 662 treated with MMC (1.1%). Five eyes developed blebitis; six eyes developed endophthalmitis. Bleb related infection developed an average of 3.1 (1.6) (range 0.4 to 6.0) years after trabeculectomy. All eyes had avascular or hypovascular blebs that were cystic in shape before infection and all eyes had reduced intraocular pressure. Early wound leaks and chronic, intermittent bleb leaks were identified to be risk factors for the bleb related infection. CONCLUSION: The incidence of delayed onset, bleb related infection after trabeculectomy with antiproliferative treatment is similar to that after trabeculectomy without antiproliferatives.

Adolescent↗

Ocular manifestations of familial amyloidotic polyneuropathy type I: long-term follow up.

AIMS: To obtain precise information on ocular manifestations of familial amyloidotic polyneuropathy (FAP) type I, the incidence of five main ocular manifestations--abnormal conjunctival vessels (ACV), keratoconjunctivitis sicca (KCS), pupillary abnormality, vitreous opacity, and glaucoma, were compared through long term follow up. METHODS: Ocular examinations were performed in 37 FAP type I patients (Met30) from once to 12 times over a period of 1 to 12 years and 7 months. RESULTS: The following incidences were observed on initial examination of each patient with FAP: ACV in 75.5%, pupillary abnormalities in 43.2%, KCS in 40.5%, glaucoma in 5.4%, and vitreous opacity in 5.4%. All ocular manifestations increased with the progression of FAP, and the incidence of ACV reached 100% during follow up: this may be helpful in the diagnosis of FAP. CONCLUSION: Since no precise statistical ocular study on FAP with long term follow up has been performed, this report may provide important information to help elucidate the mechanism of the amyloid distributing process in the amyloid targeted organs of FAP and to provide the natural course of ocular manifestations of FAP.

Adult↗

Bronchial hyperreactivity in patients with familial amyloidotic polyneuropathy and autonomic neuropathy.

To investigate the role of autonomic regulation on airway reactivity, we performed bronchial inhalation tests of methacholine (MCh) and histamine (Hist) in Japanese patients with familial amyloidotic polyneuropathy (FAP) and autonomic neuropathy. First we examined the FEV1 and Raw in seven patients with FAP and in six normal subjects, then we administered aerosols of increasing concentrations of MCh (0.075 to 25 mg/ml) at about 5-min intervals via a nebulizer controlled by a dosimeter. We measured the FEV1 until either the concentration of MCh producing a 20% reduction from the basal value (PD20) or the maximal concentration was reached. Five of the seven patients with FAP showed bronchial hyperreactivity to MCh, and PD20 to MCh was significantly lower than that of the normal subjects (p < 0.01). Furthermore the PD20 tended to correlate inversely with the severity of autonomic neuropathy (p = 0.052). The bronchial hyperreactivity to MCh was completely blocked by pretreatment inhalation of ipratropium bromide, suggesting the muscarinic receptor-mediated mechanism. Of these five patients with hyperreactivity to MCh, three with low PD20 to MCh (< 50 units) did not respond to Hist, but two with high PD20 (> 50 units) to MCh did, suggesting different mechanisms of hyperreactivity to MCh and Hist in FAP. The PD20 to Hist significantly correlated inversely to the PD20 to MCh (p < 0.05). Histochemical examination revealed marked amyloid deposition in the vagus nerves and tracheal wall in an autopsied patient with FAP and severe autonomic symptoms. These data suggest that patients with FAP and advanced autonomic neuropathy have bronchial hyperreactivity to MCh and/or Hist, probably because of denervation supersensitivity resulting from amyloid deposition in the peripheral autonomic nerves of the airways.

Adult↗

Photoaffinity labeling of tumor promoter-binding protein (CN-TPBP) and preparation of affinity sorbent gels.

Cytosolic-nuclear tumor promoter-specific binding protein (CN-TPBP) was photoaffinity-labeled with a specific ligand, 3beta,5alpha-dihydroxycholestan-6-one (YS-64). Analysis by ODS-HPLC of peptide fragments obtained from the labeled CN-TPBP by trypsinization indicated the existence of a single specifically labeled site. Affinity gels for the purification of CN-TPBP were then prepared. As ligands for the affinity gels, 12-O-tetradecanoylphorbol 13-acetate (TPA), a typical phorbol-type tumor promoter, and benzolactam-V8-310 (BL-V8-310), a structural/biological mimic of teleocidin-class tumor promoters, were adopted. The use of these gels afforded a protein that showed a single band of 58 kDa on SDS-PAGE.

Affinity Labels↗

[Detection of mycobacterial DNA with polymerase chain reaction in eye discharge and gastric juices in a case of scleritis].

We report a case of mycobacterial scleritis in which prompt diagnosis was made by the detection of mycobacterial DNA with polymerase chain reaction (PCR) in eye discharge and gastric juices, when conventional tests were negative. A 77-year-old woman who had a past history of pulmonary tuberculosis visited the outpatient clinic of Tokai University Hospital complaining of pain in her right eye. She was diagnosed as having scleritis and uveitis. There were no indications of active tuberculosis. We examined the gastric juices, sputum, and eye discharge by microscopy, culture, and PCR for detection of mycobacterium. The results of microscopy and culture were negative, but with PCR we detected atypical mycobacterium in eye discharge and gastric juices. After oral treatment with antituberculosis agents, the patient's eye symptoms disappeared. Detecting mycobacterial DNA with PCR could be useful for early diagnosis of mycobacterial scleritis, so that treatment with antituberculosis agents could be started.

Aged↗

Human mortality in organophosphate poisonings.

We reviewed 130 admissions of organophosphate poisoning and analyzed the causes of death. Fenitrothion, malathion, dichlorvos, trichlorfon and fenitrothion/malathion were the most frequent chemicals involved. Mortality was 25% (32/130); delay in discovery and transport (18 cases), insufficient respiratory management (8 cases), and severe underlying or co-existing diseases (6 cases) were noted in the lethalities. Insufficient respiratory management consisted of delay in endotracheal intubation (5 cases) and failure in weaning (3 cases). About 3/4 of the severely serum cholinesterase-depressed cases needed ventilators. This suggests that better respiratory management would improve the outcome of organophosphate poisonings. Close observation of the clinical symptoms is essential, and detection of changes in serum cholinesterase may be helpful.

Adolescent↗