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Biomedical subjects

Y Ando

Publications and source records attributed to Y Ando.

At least 307 records · Page 17Linked to original sources

Bactericidal effect of erbium YAG laser on periodontopathic bacteria.

BACKGROUND AND OBJECTIVE: Recently Erbium (Er) YAG laser has been developed for dentistry. It may be suitable for periodontal therapy. This study examined the bactericidal effect of the Er: YAG laser on periodontopathic bacteria in vitro. STUDY DESIGN/MATERIALS AND METHODS: After spreading the bacterial suspension of Porphyromonas gingivalis or Actinobacillus actinomycetemcomitans on agar plates, a single pulse laser was applied to the agar plates at the energy density of 0.04-2.6 J/cm2. The growth of the bacterial colonies on the lased agar plates was examined after anaerobic culture. P. gingivalis colonies were also individually exposed to the single pulse laser at the energy of 1.8-10.6 J/cm2. The colony forming units of the irradiated colonies were counted. RESULTS: Growth inhibitory zones were found at the irradiated sites at the energy of about 0.3 J/cm2 and higher. The survival ratios of the viable bacteria in the lased P. gingivalis colonies decreased significantly at the energy of 7.1 and 10.6 J/cm2, as compared with that of the control. CONCLUSION: These findings suggest that the Er:YAG laser has a high bactericidal potential at a low energy level.

Aggregatibacter actinomycetemcomitans↗

Protein kinase C mediates up-regulation of urokinase and its receptor in the migrating keratinocytes of wounded cultures, but urokinase is not required for movement across a substratum in vitro.

Both in cell culture and in vivo, keratinocytes that are migrating in response to a wound express enhanced levels of both urokinase-type plasminogen activator (uPA) and the uPA cell surface receptor (uPA-R). To explore the mechanism of this up-regulation, keratinocyte cultures were treated proir to wounding with a variety of metabolic and growth factor inhibitors in order to evaluate their effect on uPA and uPA-R expression. Actinomycin D and cycloheximide inhibited the up-regulation of both uPA and uPA-R, as determined by immunohistochemistry, indicating that RNA and protein syntheses are required for their induction in migrating keratinocytes. Neither removal of protein growth factors from the medium nor addition of inhibitory antibodies to a number of growth factors depressed uPA or uPA-R induction; these findings suggest that a variety of exogenous or endogenous growth factors [i.e., basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), amphiregulin, and tumor necrosis factor-alpha (TNF-alpha) do not have a critical role in the induction of uPA or uPA-R. In contrast, when protein kinase C (PKC) was either down-regulated with bryostatin 5 or inhibited with Ro31-8220 or staurosporine, the expression of both uPA and uPA-R was greatly decreased in migrating keratinocytes. Furthermore, pharmacologic activation of PKC enhanced uPA levels in non-wounded cultures. These data suggest that the enhanced expression of uPA and uPA-R in migrating keratinocytes is mediated by selective activation of PKC in these cells, perhaps secondary to alterations in the cytoskeleton induced by wounding. To test the requirement for uPA during keratinocyte migration in vitro, the extent of migration was quantified in the presence and absence of a variety of inhibitors in the wounded culture model. Migration was not altered by actinomycin D, cycloheximide, any of the above growth factor inhibitors, anti-uPA antibodies, a variety of inhibitors of uPA or plasmin enzymatic activity, or exogenous uPA. The independence of keratinocyte migration in vitro from uPA was further suggested by experiments which combined the phagokinetic assay of migration and the zymographic assay for pericellular uPA activity; no relationship was observed between pericellular uPA activity and the motility of individual cells.

Antibodies↗

Selective fallopian tube catheterisation in female infertility: clinical results and absorbed radiation dose.

Clinical results of fluoroscopic fallopian tube catheterisation and absorbed radiation doses during the procedure were evaluated in 30 infertility patients with unilateral or bilateral tubal obstruction documented on hysterosalpingography. The staged technique consisted of contrast injection through an intrauterine catheter with a vacuum cup device, ostial salpingography with the wedged catheter, and selective salpingography with a coaxial microcatheter. Of 45 fallopian tubes examined, 35 (78%) were demonstrated by the procedure, and at least one tube was newly demonstrated in 26 patients (87%). Six of these patients conceived spontaneously in the follow-up period of 1-11 months. Four pregnancies were intrauterine and 2 were ectopic. This technique provided accurate and detailed information in the diagnosis and treatment of tubal obstruction in infertility patients. The absorbed radiation dose to the ovary in the average standardised procedure was estimated to be 0.9 cGy. Further improvement in the X-ray equipment and technique is required to reduce the radiation dose.

Adult↗

Amplification of the thymidylate synthase gene in an N10-propargyl-5,8-dideazafolic-acid-resistant human leukemia, MOLT-3 cell line developed in pteroylglutamic acid, but not in leucovorin.

The types of folates used during the development of resistance to methotrexate have been suggested to play an important role in the mechanisms of established resistance. In this study, effects of reduced and oxidized folates on the development of resistance to a thymidylate synthase (TS) inhibitor, N10-propargyl-5, 8-dideazafolic acid (CB3717), were examined in the human leukemia cell line MOLT-3. MOLT-3 cells were made resistant to CB3717 by soft-agar cloning in RPMI-1640 medium with either pteroylglutamic acid (PGA) or a more physiological folate (10 nM leucovorin). A 40-fold CB3717-resistant subline developed in PGA (MOLT-3/CB3717(40)-PGA) showed amplification of the TS gene with a concomitant increased level in the gene expression. A 200-fold CB3717-resistant subline (MOLT-3/CB3717(200)-PGA), which was derived from MOLT-3/CB3717(40)-PGA, showed further enhancement of amplification of the TS gene. In contrast, even a 200-fold CB3717-resistant subline developed in leucovorin (MOLT-3/CB3717(200)-LV) showed neither amplification nor overexpression of the TS gene. Both MOLT-3/CB3717(200)-PGA and MOLT-3/CB3717(200)-LV cells showed decreased membrane transport of PGA as well as methotrexate. These results suggest that the types of folates used during the development of CB3717 resistance may play a role in resistance, and that impaired transport of PGA, in CB3717-resistant MOLT-3 cells developed in PGA, might have accelerated amplification of the TS gene.

Biological Transport↗

Is there a circadian variation in plasma concentrations of etoposide given by prolonged continuous infusion?

The prolonged continuous infusion of low-dose etoposide is a new approach to treating cancer. Whether or not a circadian variation in the plasma levels of etoposide existed was investigated in nine patients with non-small-cell lung cancer. Etoposide was infused for 14 days and blood samples were obtained every 4 h for 1 day. There was no significant circadian variation, and the observed small within-day variations seemed to lack clinical significance.

Aged↗

Pharmacodynamic modeling of prolonged administration of etoposide.

PURPOSE: A refined pharmacodynamic model for toxicity is necessary for successful adaptive control of the administration of an anticancer drug to avoid toxicity. We sought to establish a pharmacodynamic model of leukopenia in a 14-day administration of etoposide. METHODS: Pharmacokinetic data of 32 patients treated with etoposide infused over 14 days in a phase I study (20 patients) or in an adaptive control study (12 patients) were used to develop a model for the prediction of a leukocyte nadir count. The concentrations of both estimated unbound and total etoposide at steady state, as well as patient demographic factors, were included in linear and nonlinear models. The unbound fraction of etoposide was estimated using an equation based on serum albumin and total bilirubin. The efficacy of the models was evaluated in terms of correlation coefficient (r), mean predictive error (MPE) and root mean square error (RMSE). RESULTS: For both total and unbound drug concentration, a nonlinear model predicted leukopenia more precisely and with less bias than a linear model, and unbound drug explained more variability of leukopenia than total drug concentration in both linear and nonlinear models. The best model was a nonlinear model with three variables of unbound concentration, pretreatment leukocyte count and prior treatment (r = 0.76, MPE +/- SEM = 0.07 +/- 0.17 x 10(3)/microl, RMSE = 0.95 x 10(3) microl), which was better than the best linear model. CONCLUSIONS: The nonlinear model using unbound etoposide concentration explained the interpatient variability of leukocyte nadir count to a fairly large extent. Although the model provided useful information on the pharmacodynamics of etoposide, it was still imprecise and a more refined model is necessary for application to an adaptive control study.

Antineoplastic Agents, Phytogenic↗

CD4 expression is important but not essential for infection with exogenous mouse mammary tumor virus.

We studied local events in the popliteal lymph nodes of CD4-deficient mice following foot pad injection with an MMTV strain which carries the gene for a V beta 14-specific superantigen. Injection of the V beta 14-specific MMTV induced vigorous expansion of V beta 14+ CD4+ T cells and B cells in their lymph nodes of CD4+/- heterozygous control mice. On the other hand, CD4-/- mice injected with the MMTV showed a proliferation of V beta 14+ T cells among the population of TCR alpha beta + CD4-CD8- T cells, although to a lesser extent. This phenomenon was not accompanied by vigorous B cell expansion. A PCR assay revelated that the MMTV definitely infected the lymph nodes cells of the CD4-/- mouse. However, the infectivity of the MMTV in CD4-/- mice was approximately 20 times lower than that in CD4+/- mice. These findings indicate that, in MMTV infection of CD4-deficient mice, the superantigen-reactive T cells among the population of TCR alpha beta +CD4-CD8- T cells substitute for the superantigen-reactive CD4- T cells of normal mice, and that the absence of CD4 molecules decreased the infectivity of MMTV because of insufficient expansion of the superantigen-reactive T cells.

Animals↗

An external reference for in vivo quantification of 1H spectroscopy.

We studied the validity of using an external signal reference for absolute quantification of brain metabolites. We chose cyclohexane as the signal standard. An expression of a perturbed magnetic field in diamagnetic cylindrical materials was first obtained by using a method of equivalent magnetic charges. Broadening of the spectrum in this perturbed magnetic field was then computed. We performed phantom studies. We measured the full width at half maximum (FWHM) of the cyclohexane and the signal ratio (SR) between water and cyclohexane in spheres of two different diameters, and in cylinders of various diameters and lengths. The observed FWHM and SR in the small cylinders had large variations in distribution, whereas those in the spheres and in the large cylinders had small variations. Specifically, in a cylinder with a diameter > 5 cm and with a length > 10 cm, the variation of the SR was < 1.0%. The diameter and the length of the cylinder preferably are large when a cylindrical material is adopted as an external signal standard.

Brain↗

Establishment of anti-Epstein-Barr virus (EBV) cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection.

We describe an experience of a specific immune transfer treatment in a patient with chronic active EBV infection. The patient had low anti-EBV T cell-mediated cytotoxic activity in his peripheral blood mononuclear cells (PBMC), which may have been the primary cause of the disease. An EBV-specific cytotoxic T lymphocyte (CTL) line was established from PBMC obtained from the patient's sister whose human leucocyte antigens (HLA) are identical to patient's. The patient received three courses of intravenously administered CTL at 3-week intervals. The number of the cells was increased with each course of treatment. After infusion of the T cell line, anti-EBV CTL activity was detected in the patient's PBMC. CTL activity increased markedly after the second course of immune transfer therapy. The amount of EBV DNA in the patient's plasma showed transient but repeated decreases. Serum levels of tumour necrosis factor-alpha (TNF-alpha), which had elevated before treatment, began to decrease after initiation of treatment. No adverse effects were directly associated with CTL infusions. Despite having previously received a pneumococcal vaccine and prophylactic antibiotics, the patient died of infection caused by Streptococcus pneumoniae bacteraemia 27 days after the third infusion. Although the long-term efficacy and safety of this therapy remains to be established, our findings suggest that adoptive transfer of CTL specific for EBV obtained from an HLA-matched donor might be a promising treatment for patients with chronic active EBV infection.

Child↗

Acceptability of patients with brain metastases for clinical trials of chemotherapy for metastatic non-small-cell lung cancer.

This study was conducted to determine whether patients with brain metastases from non-small-cell lung cancer (NSCLC) should be included in clinical trials of chemotherapy. Patients with metastatic NSCLC and good performance status were studied. The survival of patients with brain metastases was compared with that of patients without brain metastases. Of 100 eligible patients, 22 had brain metastases at diagnosis. The median survival time was poorer in patients with brain metastases than in other patients with metastatic NSCLC (96.5 vs. 181.5 days). However, the difference in survival was not significant on univariate analysis (p = 0.106). Multivariate analysis confirmed that the prognostic value of brain metastases was limited in this sample (p = 0.129). There was little difference in survival curves during the first 8 weeks. Patients with brain metastases who have good performance status and minimal neurologic symptoms can be observed for approximately 8 weeks in clinical trials to determine their response to chemotherapy. However, it is doubtful that patients with brain metastases would be eligible for phase III trials, in which survival is an endpoint.

Adult↗

Progressive systemic sclerosis sine scleroderma which developed after exposure to epoxy resin polymerization.

Progressive systemic sclerosis (PSS) sine scleroderma is well known as a special form of scleroderma. Because of its rarity, its pathogenesis has not yet been elucidated. We experienced a 33-year-old man who developed PSS sine scleroderma while working with epoxy resin polymerization. He had short white frenulum linguae, diffuse hyperpigmentation and facial telangiectasia, positive antinuclear antibody, and pulmonary dysfunction, but not acrosclerosis or sclerodactylia. Modest dermal collagen proliferation in the forearm skin confirmed PSS sine scleroderma. Epoxy resin polymerizer appears to be a potent causative agent for PSS sine scleroderma as well as for generalized morphea-like PSS.

Adult↗

Influence of paternal (252) Cf neutron exposure on abnormal sperm, embryonal lethality, and liver tumorigenesis in the F(1) offspring of mice.

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with (252) Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or three months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) (P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F(1) generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by (252) Cf neutron irradiation.

Animals↗

Gastric tumorigenicity of 1,2-dimethylhydrazine on the background of gastric intestinal metaplasia induced by X-irradiation in CD (SD) rats.

Five-week-old male CD (SD) rats were X-irradiated with a total of 20 Gy in 2 equal fractions with a 3-day interval. After the second irradiation, rats were fed normal diet supplemented with 1% sodium chloride, which is known to increase intestinal metaplasia. 1,2-Dimethylhydrazine (DMH) solution was injected i.m. into the back musculature at a dose of 20 mg/kg body weight weekly for 10 weeks, beginning 20 weeks after the final irradiation. Twelve months after the initial carcinogen treatment, gastric tumors in the glandular stomach were observed in 2 (3 lesions) of 30 animals in the X-irradiated and DMH-treated group fed diet supplemented with 1% sodium chloride. No gastric tumors were observed in the group which excluded X-irradiation from the experimental protocol.

1,2-Dimethylhydrazine↗

Therapeutic drug monitoring in 21-day oral etoposide treatment for lung cancer.

We aimed to determine whether or not therapeutic drug monitoring is applicable to 21-day oral etoposide treatment for lung cancer. As the starting dose, a 25-mg capsule of etoposide was taken orally three times daily (75 mg/body). To achieve the target concentration range of 1.0 to 1.5 micrograms/ml, the dose was changed to two (50 mg/body) or four (100 mg/body) times a day from day 5, depending on the mean concentration obtained on days 3 and 4 (Cbefore). The mean concentration was calculated by use of a limited sampling model we constructed previously. Among 26 courses in 15 patients, two patients experienced grade 4 leukopenia plus neutropenia, and one of them died on day 20. Because nausea/emesis prevented the planned dose escalation in one patient, we excluded two courses of this patient from the pharmacokinetic analysis of dose modification. Among 5 courses with dose reduction, the Cbefore of 1.7 +/- 0.1 (microgram/ml, mean +/- SE) was decreased to 1.3 +/- 0.2 after day 5 (Cafter). Among 7 courses with dose escalation, the Cbefore of 0.9 +/- 0.0 was increased to the Cafter of 1.2 +/- 0.1. Among the remaining 12 courses without dose modification, the Cbefore and the Cafter were 1.2 +/- 0.0 and 1.3 +/- 0.1, respectively. Hematologic toxicities tended to correlate with the drug concentration. TDM is thus applicable to oral etoposide given according to this schedule, and a larger study is now needed to confirm that the therapeutic efficacy is improved by introducing TDM.

Administration, Oral↗

Therapeutic drug monitoring of etoposide in a 14-day infusion for non-small-cell lung cancer.

We investigated whether a constant plasma concentration could be obtained by the individualized administration of low-dose, prolonged-infusional etoposide. Etoposide was infused for 14 days at 40 mg/m2/day initially in patients with inoperable non-small-cell lung cancer. The infusion rate was modified based upon the etoposide concentration at 24 h following the initiation of the infusion (C24) to achieve a target concentration of 1.5 microgram/ml. We postulated that severe toxicities could be avoided by maintaining the steady-state concentration at less than 2 microgram/ml, while antitumor activity could be expected if the steady-state concentration was maintained at more than 1 microgram/ml. In a total of 21 courses in 12 patients, the mean etoposide dose was 35+/-6 mg/m2 daily. The C24 was 1.8+/-0.4 microgram/ml and ranged from 1.1 to 2.9 microgram/ml. Following dose modification, the mean concentration from 96 to 336 h (C mean) was 1.6+/-0.2 microgram/ml and ranged from 1.2 to 2.0 microgram/ml. The toxicities were well-tolerated except for one patient with WHO grade 4 leukopenia and neutropenia who developed infectious complications. There were no treatment-related deaths. Following dose modification, the inter-patient variability was decreased successfully. Although this pharmacologically-guided method needs to be validated using more patients, it could be used for therapeutic drug monitoring.

Aged↗

Case report: varicella-zoster virus myelitis--serial MR findings.

The authors describe a 32-year-old male in whom herpes zoster of the left upper extremity was complicated by the development of cervical myelitis. Contrast enhancement and abnormal signal intensity on T1 and T2 weighted images was seen at C1-C6 levels in the spinal cord and medulla. There was also slight enlargement of the cord at these levels. On serial MR imaging the degree of enhancement changed from marked to none with corresponding clinical improvement.

Adult↗