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Biomedical subjects

A Kubo

Publications and source records attributed to A Kubo.

At least 163 records · Page 9Linked to original sources

Amine effect on phenylboronic acid complex with glucose under physiological pH in aqueous solution.

A new "intelligent' polymer system was developed utilizing the binding and exchange of phenylboronic acid (PBA) with polyols and/or glucose. In this improved system, an amine component was incorporated into the polymer chain along with PBA, to enhance binding between PBA and glucose under physiological conditions. The PBA-based polymer was formed by free-radical copolymerization of 3-methacrylamidophenylboronic acid (MAPB) with comonomers, N,N-dimethylaminopropylacrylamide (DMAPAA) and acrylamide (AAm) in the presence of N,N'-methylenebis(acrylamide) (Bis-AAm) as a cross-linker. The proportion of the amount of PBA groups complexed with glucose vs total amount of PBA groups was determined by the batch method. Compared to PBA copolymers synthesized without amine component, the proportion increased as a function of the amine content as well as the pH of the buffer. These results confirm that the interaction of neighboring amines (unprotonated) to PBA strengthens the binding with glucose, especially at pH 7.4 and above. This new PBA-amine copolymer is promising as a material useful for polyol separation, protection of polyols, and possibly, as an insulin delivery device.

Acrylamide↗

Prevention of cardiac hypertrophy by a sub-antihypertensive dose of the alpha 1-adrenergic antagonist bunazosin in Dahl salt-sensitive rats.

To assess the protective effect of an alpha 1-blocker on the development of cardiac hypertrophy, the selective alpha 1-receptor antagonist bunazosin (2 mg/kg/d, by oral gavage and in drinking water) was given to male Dahl salt-sensitive rats fed a 4% NaCl diet for 7 weeks. Control animals received water only by the same method. Treatment with bunazosin was started when the animals were 7 weeks of age. Blood pressure, pulse rates, and body weight were measured every week during the experiment. Urine was collected for 24 h on the final day of the experiment. All animals were killed by decapitation, blood was collected, and the heart was removed. In both the treated and control groups, time-dependent increase in blood pressure and body weight were observed, and there were no significant differences between the groups in blood pressure or body weight during the experiment. Pulse rate remained unchanged in both groups throughout the experiment. The left ventricular weight/body weight ratio and the left ventricular tissue DNA content were significantly lower in the rats receiving bunazosin than in the control rats. Plasma renin activity, plasma aldosterone, and plasma atrial natriuretic peptide did not differ significantly between the two groups. No significant differences in glomerular filtration rate, urine volume, sodium excretion, urinary metanephrine excretion, and urinary normetanephrine excretion were noted between the two groups. The results indicate that a sub-antihypertensive dose of bunazosin can inhibit the development of cardiac hypertrophy without suppression of the pressure load, suggesting an important role of alpha 1-adrenergic receptors in the pathogenesis of cardiac hypertrophy following the development of hypertension.

Adrenergic alpha-Antagonists↗

[A case report of concomitant UFT-E and CDDP against lung epidermoid carcinoma].

A 52-year-old male with the chief complaint of hemo-sputum was diagnosed after detailed examination as epidermoid carcinoma in the right upper lobe bronchus through the bifurcation. Thoracotomy revealed infiltration of carcinoma into the right main pulmonary artery and the superior vena cava, which could not be excised. Subsequent postoperative radiotherapy (69 Gy) showed NC. Then concomitant administration of UFT-E and a low dose of CDDP was started on an outpatient basis. After the third course of treatment (six weeks per course), a significant reduction was noted in the size of the carcinoma. Bronchoscopy revealed CR with the elimination of carcinoma to mere traces. Besides the myelosuppression seen at the end of the second course of treatment, which resulted in a two-week hospitalization for blood transfusion, no adverse effect prevented the patient from continuing the outpatient treatment courses and from returning to work. We consider that the treatment was very successful not only for its effectiveness in reducing the carcinoma but also for the high QOL achieved.

Administration, Oral↗

[Palliation of brain metastases: factors associated with survival].

One hundred ten patients with brain metastases (76 lung cancer, 11 breast cancer, 7 colorectal cancer and others) were treated with radiotherapy, and the results were retrospectively evaluated. Neurologic symptoms were improved in 66% of patients. The relationship between improvement of neurologic symptoms and several factors, including irradiation dose, primary lesion, histology, term between first treatment and recurrence, clinical symptoms and CT findings, was analyzed. There was no significant correlation between symptom relief and these factors except for the number of metastatic lesions. Four of 110 patients could survive more than 2 years after radiotherapy: one with lung cancer, one with breast cancer, one with rectum cancer and one with uterine cancer. The factors that were analyzed for symptom relief were also studied to determine their effect on the survival of lung cancer patients with brain metastases. The patients who had higher dose irradiation (50 Gy) of improvement of neurological symptoms after radiotherapy survived significantly longer than those who had 30 Gy of irradiation or no symptom relief. Multivariate analysis of these factors showed that improvement of symptoms and irradiation dose were similarly important prognostic factors, whereas the others were not correlated with survival.

Brain Neoplasms↗

[Theoretical considerations of dose-rate effect for clinical application: a study of pulsed brachytherapy].

Pulsed brachytherapy is starting to be used for patients with various kinds of carcinoma, in the expectation of fair treatment results without increasing the late radiation-induced damage. We calculated the early and late biologically effective dose (BED) of this modality to predict early and late radiation damage based on the linear-quadratic model (L-Q model). The way to set the values of alpha/beta and mu (factor of repair) in the L-Q model remains controversial. The value of alpha/beta has been fixed at 3Gy for the late effect and 10Gy for the early effect in recent studies. In this study, we applied these alpha/beta values to calculate the BED, however, the effects of its alteration ranged from 0.5Gy through 15Gy on BED were also analysed. We assumed mu = 0.5 (T1/2 = 1-2 hours) in this study, but we also tried to examine the effects of its variation. Our results indicate that pulsed brachytherapy is a safe treatment procedure even if the dose-rate ranges from 1Gy/hr through 100Gy/hr, but the fractionation number should be increased when using a very high dose rate. Pulsed brachytherapy should be applied cautiously for tissues with a small mu value, such as the spinal cord, because an extremely high late BED would be expected in such cases.

Brachytherapy↗

[Pitfalls of hyperfractionation: theoretical considerations of effect of repair time on late radiation damage].

The need of radiation therapy in cancer treatment is increasing, however, the dose of radiation is limited by its late effects on normal tissues. Hyperfractionated radiotherapy was applied to patients with various kinds of carcinomas in the 1980s, expecting to improve tumor control rates. Some reports showed that the total radiation dose could be increased without increasing late radiation damage by using hyperfractionated radiotherapy. We calculated the early and late biologically effective doses (BED) for conventional and hyperfractionated radiotherapy to predict the early and late radiation damage based on the linear-quadratic model (L-Q model). Setting the values of the alpha/beta ratio and t1/2 (half time repair) in the L-Q model is still controversial, and few reports deal with t1/2. Assuming t1/2 = 0.5 hour, the total radiation dose can be up to 71 Gy by hyperfractionated schedule (1.2Gy/fr. 2 times/day) without increasing the late BED of conventional schedule (2Gy/day, total 60Gy). However, the late BED should be increased in tissues with a larger t1/2 value, even if applying the same hyperfractionated schedule. Thus, it is not recommended to apply the same hyperfractionated protocol to all organs.

Humans↗

[Assessment of clinical utility of 111In-DTPA-IgG scintigraphy in the detection of inflammation/infection--a report of multicenter phase II clinical trials].

A Phase II clinical study was performed in patients with strongly suspected focal sites of inflammation/infection to investigate clinical utility of 111In-DTPA-IgG. Neither adverse effects nor abnormal laboratory changes were noted in the all cases. Out of 59 patients, the clinical utility was evaluated in 56 patients with a total of 67 suspicious sites (19 in thorax, 13 in abdomen and pelvis, 30 in musculoskeletal system, and 5 in other regions). True positive results were obtained in 100% of lesions in the thorax (13/13) and the musculoskeletal system (26/26). There were three false negative and five false positive results. Overall sensitivity and specificity was 94.0% and 70.6%, respectively. Most of the true positive scintigram with the best image quality was acquired at Day 1 or Day 2 post-injection. A dose of 80 MBq was considered to be a practical dose for imaging. Our study indicates that 111In-DTPA-IgG is a safe and promising imaging agent for the detection of inflammation/infection, and that it is reasonable to proceed with Phase III studies to further evaluate clinical utility of the agent.

Adult↗

[Biological effect of carbon beams on cultured human cells].

This study was performed to determine the biological effect of carbon beams on 13 human tumor cells, in comparison with 200 KVp X-rays. Carbon beams were generated by the Riken Ring Cyclotron. The RBE (relative biological effectiveness) values were distributed from 1.46 to 2.20 for LET of 20 ke V/micron, and 2.29-3.54 for 80 keV/micron. The RBEs were increased in all cell lines as the LET of carbon beams was increased from 20 to 80 keV/micron. There was no significant difference in radiosensitivity between cells from adenocarcinoma and those from squamous cell carcinoma. The relationship between the radiosensitivity of cells to X-rays and RBE was analyzed, but no significant correlation was suggested. Several survival curves of 20-40 keV/micron carbon beam irradiation showed the initial shoulders and the recovery ratios between two split doses were determined. Recovery was observed for LET of 20 keV/micron but not for that of 40 keV/micron. Furthermore, recovery ratios were 1.0-1.8, smaller than those for X-rays (1.5-2.4).

Adenocarcinoma↗

[Mutation induction by heavy ion beams and X-rays: analysis with cultured cell line].

This study was performed to determine the biological effects of heavy ion beams on cultured cells. V79 cells were irradiated with carbon or neon beams or X-rays, and cell survivals was calculated by the colony assay method. The Do values for 150 kVp X-rays, 20 keV/micron and 80 keV/micron carbon beams, and 80 keV/micron neon beams were 2.2Gy, 1.8Gy, 1.0Gy and 1.4Gy, respectively. After 7-10 day expression periods, the mutation frequencies at the hypoxanthine-guanine phosphribosyl transferase (hprt) locus were analyzed from the numbers of colonies formed in media supplemented with 6-thioguanine. An extremely higher frequency of mutation was observed with heavy ion beams compared with X-rays. Both cell killing effect and the mutation induction were enhanced when the LET of carbon beams was increased from 20 to 80 keV/micron. These results mean that carbon beams had a stronger cell-killing effect than X-rays, but also carried a high risk of mutation induction. On the other hand, neon beams yielded cell survival curves similar to those of carbon beams, but they had a smaller mutation induction effect than carbon beams. The effect of fractionated irradiation (3 hr interval) on cell survival and mutation frequency were also examined. When cells were irradiated with X-rays, cell survival was increased by fractionation, but the mutation frequency was not modified. Irradiating cells with fractionated carbon beams, survival curves were not affected, but mutation frequency was reduced.

Animals↗

[Diagnostic accuracy of 201T1 SPECT.MRI in brain diseases and inter-reader variance of diagnostic performance].

Fifteen-four studies of 201T1 brain tumor SPECT were independently interpreted by 9 nuclear medicine physicians with and without reference magnetic resonance images in 2 separate sessions to define an effect of referring images, and inter-observer variations. The physicians were requested to detect foci of abnormal deposits, and to discriminate whether they were malignant or not according to 5-grade scaling of subjective diagnostic confidence. Receiver-operating characteristics (ROC) analysis was performed. Mean sensitivity for presence of lesions (SEP), and sensitivity and specificity for malignancy of 201T1 SPECT were 84, and 53 and 55%, which were changed to 94, and 74 and 55% after referring to the MR images. The SFP was significantly improved (p < 0.05), but sensitivity and specificity for malignancy, assessed by areas under the ROC curves, were not significantly improved. Inter-observer variation of the SFP was significantly reduced with addition of the referring MR images. Cerebral lobar localization of lesions by SPECT showed great inter-observer variations (true localization ranged from 30 to 68.4%). It is concluded that 201T1 brain tumor SPECT has moderate sensitivity and specificity for malignancy, which is not improved by addition of anatomical reference images, that additional MR images reduce inter-observer variation of confidence on lesion presence, and that SPECT localization of lesions has great inter-observer variations.

Adolescent↗

[Enlargement of effective field of view in gamma-ray transmission CT using a fan-beam geometry].

Quantitative SPECT images require to correct attenuation of the gamma rays in the body, therefore, it is desired to obtain a true attenuation map measured by gamma-ray transmission CT. Many methods and geometries of the gamma-ray transmission data acquisition system have been proposed, however, there is a limitation in the size of the scintillator and this causes a serious artifact in reconstructed images of thorax. In this paper, we formulated the relation between the detector length and the effective field of view for following data acquisition geometries in gamma-ray transmission CT; a detector with a symmetric fan-beam collimator which has long focal length, two detectors with a symmetric fan-beam collimator, and a detector with an asymmetric fan-beam collimator.

Artifacts↗

[Scatter and attenuation correction for quantitative myocardial SPECT imaging].

We performed scatter and attenuation compensation in 201Tl myocardial SPECT using the triple-energy-window (TEW) scatter correction method and 99mTc transmission scan (TCT). A dual-headed SPECT gammacamera system equipped with parallel-hole collimators was employed for imaging and a sheet source for TCT was attached to the surface of one of the two detectors. Two imaging protocols, a sequential mode and a simultaneous mode, were examined. In the sequential mode, TCT was performed prior to the administration of the tracer and then ECT was carried out. On the other hand, the injection was followed by a simultaneous transmission-emission scan, in the simultaneous mode. Results of phantom studies showed that reconstructed SPECT values of the whole myocardium were almost equal to the true value with errors of less than 5 per cent, and that more homogeneous images were obtained by performing scatter and attenuation correction. We conclude that this correction method was clinically practical and cost-effective because it uses parallel-hole collimators and does not require fan-beam collimators which may produce truncation artifacts.

Heart↗

[The long-term results of the irradiation therapy for the dural arteriovenous malformation].

Although radiotherapy has been used to treat non-neoplastic vascular diseases, it is not widely accepted as a standardized treatment for dural arteriovenous malformations (DAVM). The uncertainties regarding the therapeutic outcome and the benign nature of DAVM are the major factors that limit the indication of radiotherapy. In an attempt to assess the long-term benefits and risks of the treatment, we analyzed 24 patients with DAVM treated with radiotherapy. The cavernous sinuses were involved in 12 and the transversesigmoid sinuses in 12. Doses ranging from 10 to 56 Gy (median 44.9 Gy) were delivered by multiple fractionation. In terms of clinical improvement, complete response was achieved in 19 patients and partial response in five. Four patients had recurrence of symptoms; two patients were reirradiated with the result of good symptomatic relief, one patient was successfully treated with transarterial embolization and the other patient with less disabling symptoms was managed conservatively. No adverse side effects attributed to radiation were encountered during the follow-up period of 0.5-17 years (median 8.5 years). Radiotherapy is a safe and effective method for the treatment of DAVM and is warranted in patients who are unsuitable for transarterial embolization or surgical procedure.

Adult↗

[Prognostic factors of nasopharyngeal carcinoma treated by radiotherapy].

This study was a retrospective analysis of 82 patients with histologically confirmed nasopharyngeal carcinoma, who were treated at Keio University Hospital from March 1983 to March 1993. We studied all cases(62% of them were stage IV) with regard to their prognostic factors and chronic side effects induced by radiation. All patients were received extended-field radiotherapy from the base of the skull to the supraclavicular lymph node area. The five- and ten-year overall survival rates for the entire group were 59% and 49%, respectively. Three stage I patients were alive without recurrence or metastases for more than 5 years. The ten-year survival rate stage II-III for patients (23 patients) was 78%, and for stage IV (56 patients) 37%. The five-year survival rate of patients in T2-3 group without lymph node metastasis was 88%, while it was reduced to 55% for patients with metastasis. The prognosis of T4 patients was very poor: their five-year survival rate was 37% with lymph node metastasis, and 35%, without lymph node metastasis. Patients under 46 years old showed an increased survival rate compared with patients over 46 years old. Patients who completed less than 52 days of radiation therapy found to have a better prognosis than those receiving radiation for a longer period. Our multivariate analysis indicated that age, radiation period and N-factor were statistically significant in influencing prognosis. Hearing loss occurred relatively high with 20% of cumulative incidence in our study, probably because they received radiation therapy with the extended field including bilateral middle and inner ear. Extended-field radiotherapy for patients with nasopharyngeal carcinoma might contribute to improving their cure-rate, and precise radiation planning is warranted to avoid the late complications such as hearing loss.

Adenocarcinoma↗

[Effectiveness of the radioactive strontium (89Sr) chloride agent, SMS.2P for pain palliation in patients with metastatic bone tumor in phase III multicenter clinical trial].

The phase III clinical trial of strontium-89 chloride agent (SMS.2P) was performed in 90 patients with painful bone metastases secondary to prostate (53), breast (18) and other types of cancer (19). Some patients experienced a transient increase in pain or nausea and vomiting. However both symptoms subsided and serious side effects were not observed in any of the patients. As reported, we confirmed some abnormal changes in peripheral blood picture. A decrease in the number of white blood cells and platelets was considered to be partly a result of bone marrow suppression due to 89Sr irradiation. Pain was substantially improved after 89Sr therapy in 58% of the patients and there was some alleviation in 12%. The release from pain was accompanied by an improved quality of life for these patients including sleep patterns and morbidity. Some patients were able to resume their former life styles. Most of the improved patients experienced pain relief from days to one week following 89Sr therapy and in half cases, this remained effective for 2 or 3 months. There were even cases in which the pain relief continued over an observation period of time of clinical study.

Adult↗

Autocrine growth of transitional cell carcinoma of the bladder induced by granulocyte-colony stimulating factor.

Granulocyte-colony stimulating factor (G-CSF) produced by nonhematopoietic malignant cells has been reported to be capable of inducing a leukemoid reaction in the host through intense stimulation of leukocyte production. Furthermore, this is frequently associated with aggressive tumor cell growth and a detrimental clinical outcome. In this study, we identified bladder cancer cells producing G-CSF with the expression of the functional receptor, which provides direct evidence of autocrine growth of bladder cancer cells induced by G-CSF. The cancer cells used in this study were obtained from a 76-year-old man who had a metastatic transitional cell carcinoma of the bladder and who demonstrated marked leukocytosis, his peripheral blood leukocyte count was 94,900 leukocytes/mm3, and his serum G-CSF level was 103 pg/ml. The culture medium in which the cancer cells were grown exclusively contained a significant amount of G-CSF (5560 pg/ml). Significant G-CSF mRNA expression and G-CSF receptor mRNA expression in the cultured cells were demonstrated by the reverse transcription-PCR method. In addition, binding studies with the use of radiolabeled recombinant G-CSF demonstrated the presence of high-affinity G-CSF binding receptors on the cultured cancer cells. Finally, the proliferation of the cultured cancer cells was stimulated by exogenous G-CSF administration, and this stimulation was inhibited by adding anti-G-CSF antibody, as demonstrated by both the flow cytometric bromodeoxyuridine incorporation technique and the [3H]thymidine incorporation assay. These results strongly suggest that G-CSF production by the bladder cancer cells studied augments autocrine growth. Therefore, we recommend exercising caution in the clinical use of G-CSF for bladder cancer patients.

Aged↗

(E)-3-tridecen-2-one, an antibiotic from the interdigital glands of black-tailed deer Odocoileus hemionus columbianus.

(E)-3-tridecen-2-one, the major volatile component of interdigital gland extracts from the black-tailed deer, Odocoileus hemionus columbianus, inhibited the growth of gram-positive bacteria and fungi. The bacteria, Propionibacterium acnes, and the fungi, Trichophyton mentagrophytes had a minimum inhibitory concentration (MIC) of 12.5 micrograms/mL and 25 micrograms/mL, respectively.

Alkenes↗