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Biomedical subjects

H Tsujii

Publications and source records attributed to H Tsujii.

At least 73 records · Page 4Linked to original sources

Prostaglandin E2 and rat liver regeneration.

BACKGROUND: Prostaglandin (PG) is reported to be involved in hepatic regeneration. However, little is known about the detailed relation in PG-induced stimulation of the proliferation. The present study was attempted to elucidate the relation. METHODS: The serial change of PGE2 level released from the regenerating rat liver and the effect of PGE2 on the proliferation of rat hepatocytes were studied, with special reference to PGE2 binding and cyclic AMP (cAMP). RESULTS: The PGE2 level increased 3 hours and 10 hours after partial hepatectomy. Timings of these increases seemed to coincide with those of the first and second increase of cAMP in the liver before the initiation of DNA synthesis. DNA synthesis of hepatocytes in primary culture between 24 and 36 hours, 36 and 48 hours, and 48 and 60 hours of culture were significantly enhanced by addition of PGE2 between 4 and 24 hours of culture at concentrations of 2 nmol/L to 1 mumol/L, 2 nmol/L to 200 nmol/L, and 5 mumol/L to 10 mumol/L, and 2 nmol/L and 10 mumol/L, respectively. Enhancement of DNA synthesis with PGE2 at concentrations less than 1 mumol/L seemed to be associated with the high-affinity binding and that at high concentrations with the low-affinity binding. Intracellular cAMP level in the hepatocytes increased during culture, and its increase was enhanced by PGE2 addition. CONCLUSIONS: It is suggested that PGE2 production in the liver increases biphasically during hepatic regeneration and that PGE2 enhances the proliferation of hepatocytes by a specific receptor-mediated process, which is largely associated with cAMP-dependent process.

Animals↗

Clinical results of fractionated proton therapy.

PURPOSE: Preliminary results of a multi-site Phase I-II clinical trial investigating the efficacy of high-energy proton beams in a wide variety of human malignancies are reported. METHODS AND MATERIALS: Since 1983 proton radiotherapy using 250 MeV proton beams produced by a booster synchrotron of the National Laboratory for High Energy Physics has been carried out at Proton Medical Research Center, University of Tsukuba. As of September 1990, a total of 147 patients received a partial or full treatment with proton beams with curative intent; 92 patients (63%) were treated with proton beams alone and 55 patients (37%) with combined photon and proton beams. There were 91 males and the mean age was 61.8 years old. The follow-up observation period ranged from 10 to 97 months. With regard to a total tumor dose, nearly 80% of patients received 70 Gy or more and 53% received 80 Gy or more. While dose-fractionations used depended upon tumor sites, the large majority of patients received substantially high radiation doses in terms of larger total doses (> 70 Gy) and larger fraction sizes (> 2.5 Gy) than those traditionally used. This fractionation regimen has been used because of limited availability of the accelerator or a shortage of machine time (27-30 weeks/year, 3-3.5 hr/day), and also by the expectation that the superior dose distribution possible with protons will permit administration of high radiation doses without increasing morbidities. In connection with this, we have determined the target volume by setting margins around the tumor boundary as practically small as possible, ranging from 5 to 10 mm. RESULTS AND CONCLUSIONS: The current trial has been based on a site and dose searching program, hence a wide variety of tumor sites including the aerodigestive organs has been treated. So far, our judgment is that proton therapy has proven of potential advantage in treatment of the lung, esophageal, liver, uterine cervix, prostate, and head and neck malignancies; and of possible value in treatment of high-grade gliomas, and gastric, urinary bladder, and pediatric tumors.

Adolescent↗

Proton radiation therapy for clivus chordoma--case report.

A 57-year-old male with clival chordoma developed severe hoarseness, dysphagia, and dysphonia 1 month after a second removal of the tumor. Magnetic resonance imaging demonstrated a mass 10 cm in diameter in the region of the middle clivus enhanced inhomogeneously by gadolinium-diethylenetriaminepentaacetic acid, and a defect in the skull base. There was evidence of compression of the anterior surface of the pons. He received proton irradiation employing a pair of parallel opposed lateral proton beams. The dose aimed at the tumor mass was 75.5 Gy, to the pharyngeal wall less than 38 Gy, and to the anterior portion of the pons less than 30 Gy. Time dose and fractionation factor was calculated at 148. Thirty-one months following treatment, he was free of clinical neurological sequelae. Proton therapy should be considered in treatment planning following initial surgical removal or for inoperable clivus chordoma.

Chordoma↗

[Proton radiotherapy].

Protons have an ideal characteristic for radiotherapy in terms of dose distribution, and the clinical values of proton radiotherapy have been recognized over thirty years. The outstanding clinical results for the selected categories of patients such as uveal melanoma, sarcoma of the skull base and/or the cervical spine, and relatively slow-growing, intracranial lesions treated with proton therapy have already been well reported through many articles. In recent years, the technological development has produced proton accelerator that generates protons appropriate for the treatment of deep-seated tumors, and isocentric gantry system. It will be necessary however, to evaluate and establish the efficacy of proton radiotherapy for tumors that have not previously been studied during the next decade. The number of treatment facilities has been steadily increased over the world. Proton radiotherapy is expected to play an important role in cancer treatment in the near future.

Humans↗

[HCV].

HCV is an RNA-virus which contains a positive-strand RNA genome. The RT-PCR method is used to detect the HCV-RNA in plasma. Quantification of HCV-RNA is difficult, but it can now be done by a competitive RT-PCR method developed recently. Genotypes of HCV can be classified into at least six basic groups, genotype I-IV can be distinguished by RT-PCR with type-specific primers. We report here that the prevalence of type-I, II, III, IV, and mixed type (II + IV) are 1.0%, 90.3%, 3.2%, 3.2%, and 2.2%, respectively. The DNA-probe method was recently developed and is less sensitive than the RT-PCR method, but simple and handy to detect HCV-RNA. Patients with chronic active hepatitis C received 3MU (9MU) of natural-interferon alpha (recombinant-interferon alpha 2a) daily for two weeks followed by three times a week for 22 weeks. Although the relationship between genotype of HCV and response to interferon-alpha therapy is unclear, the titer of HCV-RNA was significantly lower in long-term responders (ALT level remained within the normal range during the 12 weeks after the end of therapy) and short-term responders (ALT level rose again during the 12 weeks after the end of therapy) than that in nonresponders (ALT level was not normalized in spite of interferon-alpha therapy).

Adult↗

[Proton irradiation synchronized with respiratory cycle].

A sensitive strain gauge was used to detect the movement of the chest wall in order to synchronize an irradiation control system with the respiratory cycle. The output timing signal from the system is transferred to the proton accelerator for synchronized irradiation. The timing signal is set during the expiratory phase at a duration of 1.5 to 2 seconds. The efficacy of this method was evaluated by dose volume histogram based on the treatment planning program with CT images. The volume spared by this novel method was calculated in several cases, and results suggest that the method was highly effective.

Humans↗

Indications of particle radiation therapy in the treatment of carcinoma of the esophagus.

Studies were made to evaluate the role of radiations in the treatment of carcinoma of the esophagus to confirm indications for charged particles. Results of the studies showed that prognosis of the patients treated with radiations depend strongly on length of tumor as well as on invasion of tumor cells into the adventitia of the esophagus. It was concluded that patients suffering from carcinoma of the esophagus less than 8 cm length are indicated for particle radiations.

Esophageal Neoplasms↗

High-energy proton beam radiation therapy for gynecologic malignancies. Potential of proton beam as an alternative to brachytherapy.

Fifteen patients with advanced gynecologic malignancies were treated with high-energy proton beam radiation therapy (RT) at the Particle Radiation Medical Science Center (PARMS), Tsukuba University, Japan, from 1983 to 1987. The potential of proton beam RT as an alternative to conventional brachytherapy was evaluated. Except for one local recurrence, 14 of 15 patients were locoregionally controlled for 15 to 57 months. Two-year local control rate and 2-year survival rate were 92.3% and 93.3%, respectively. Two cases of transient, radiation-induced proctitis (neither of which required surgical treatment) were the only complications despite a target dose that exceeded 8000 cGy in most cases. The results suggest that sharply localized, high-dose proton beam RT can produce an antitumor effect equivalent to that of conventional brachytherapy.

Aged↗

Hepatitis C virus infection in patients with chronic liver diseases.

Antibodies against hepatitis C (HCV) in 512 patients were measured by an enzyme immunoassay (Ortho-HCV ELISA). The frequency of anti-HCV was 80%, 86%, 85% in nonB (NB) chronic hepatitis (CH), cirrhosis (LC), hepatocellular carcinoma (HCC), respectively; 70%, 90% in alcoholic (AL) LC, HCC; 15%, 33%, 58% in hepatitis B (HB) CH, LC, HCC, respectively. Anti-HCV positive cirrhotics had a shorter survival time and earlier development of HCC than anti-HCV negative cirrhotics. The findings suggest that HCV is a major cause of NB chronic liver diseases and may play a pathogenetic role in AL and HB liver diseases.

Adult↗

Normal brain damage after radiotherapy of brain tumours.

A total of 106 patients were examined for adverse effects to the brain from 60Co or proton radiotherapy. Radiation induced change (RIC) developed within the irradiated field 40-60 months after doses of 800-1000 neuNSD or 70 TDF and in 10-20 months after doses of more than 1700 neuNSD or 100 TDF. The incidence of RIC increased significantly with increasing age. Furthermore pathological changes like oedema and infarction in the brain tissue may be an important factor for the development of RIC in the central nervous system (CNS).

Adult↗

Alloimmune neonatal neutropenia in monozygous twins. High-dose intravenous gammaglobulin therapy.

An indirect immunofluorescence test using a flow cytometer (FACS420) was useful for detection of antineutrophil antibodies (anti-NA2 antibodies) in a case of monozygous twins with alloimmune neonatal neutropenia. When high-dose intravenous gammaglobulin (300 mg/kg for five consecutive days) was given to one twin, the increase in neutrophils was not obvious. Although neutropenia persisted for about three months, no infections were observed in either of the twins.

Autoimmune Diseases↗

[Inhibition by proton irradiation on the development of invasive bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in mice].

Fifty-five female C3H/He mice were given 0.05% N-bytyl-N-(4-hydroxybutyl) nitrosamine in their drinking water for 18 weeks. In week 19, eleven mice (group 3) were sacrificed to confirm that they all had bladder carcinoma. The remaining mice were divided into two groups. Group 1 received 20 Gy of proton irradiation over the whole pelvis, while group 2 received no treatment as a control. After 3 weeks all the animals were sacrificed and their bladders were resected to weigh and to examine histologically. The average weight of the bladder, as an index of the tumor volume, was 67.7 mg in group 1, 120.6 mg in group 2 and 106.5 mg in group 3. There was a significant differences (p less than 0.05) between group 1 and group 2. The incidences of superficial (pT1) and deeply invasive (pT2-3) bladder carcinomas were [10/18 (56%) and 8/18 (39%)] in group 1, [3/17 (18%) and 14/17 (82%)] in group 2 and [2/11 (18%) and 9/11 (82%)] in group 3, respectively. These rates of incidence were significantly different (p less than 0.05) between group 1 and group 2. However, there was no significant difference (p = 0.068) between group 1 and group 3. These results indicate that proton irradiation is effective for treatment of invasive bladder carcinoma in mice.

Animals↗

[Detection of hepatitis C virus genomes using PCR method].

Recently, an assay system for anti-hepatitis C virus antibody (HCV-Ab) was developed. However, the hepatitis C virus (HCV) itself must be detected. The polymerase chain reaction (PCR) method was used to detect the HCV-RNA genome in the plasma of patients with non-A, non-B (NANB) hepatitis related liver diseases. The PCR method is clinically useful to diagnose the early phase of HCV infection, and to judge the effect of the anti viral therapy (Interferon, etc.). Two primers were used in this study (one based on the NS5 region, another on the 5' non-coding region). Primers based on the 5' non-coding region are superior in the point of sensitivity. The PCR method is useful in diagnosing HCV infection, but special care must be taken, such as avoiding RNase contamination, and keeping the samples in a deep freezer, when using it as a routine laboratory procedure.

Genome, Viral↗

Neurenteric cysts with meningomyelocele or meningocele. Split notochord syndrome.

Two rare cases of neurenteric cysts with meningomyelocele and meningocele were treated. The mechanism of the development of these anomalies is discussed. It is considered that the terminal, dorsal part of the enteric fistula, which is produced between the endoderm and the ectoderm through a partially duplicated notochord in the development of the embryo, remains after obliteration of the fistula and, consequently, that the mucosa of the enteric remnant is inverted and projects through the skin of the back.

Abnormalities, Multiple↗

[Clinical study of proton radiotherapy in urological cancers].

Therapy with proton beam is superior to that with photon beam in concentrating the dose within a lesion. Fifteen patients with urinary malignant tumors were treated by proton irradiation during the period from June, 1985 to March, 1989 at Particle Radiation Medical Center, University of Tsukuba. Four patients were with renal cell carcinoma, five with prostatic cancer and six with bladder cancer. Treatment results were assessed by change in tumor size either three or six months after the irradiation. In all the four cases with renal cell carcinoma, the tumor sizes were found to be unchanged without any enlargement. Of the five cases with prostatic cancer, two showed that the treatment was effective and the tumor sizes in the other three cases were found to be unchanged. In three of the six cases with bladder cancer the tumors disappeared while the treatment was found effective in two other and it did not cause any enlargement of the tumor in the remaining one. Although local control of the tumor was successful in all the cases, one patient with prostatic cancer and three with bladder cancer died of cancer. Various side effects, such as radiation cystitis, were observed. This prospective therapy is expected to replace the conventional photon therapy. However, some improvement is needed to make full use of the advantageous properties in dose distribution. Combination therapy with other general therapy is required for some cases.

Aged↗

[Significance of HDL cholesterol/apolipoprotein A-I ratio].

HDL cholesterol (HDL-Ch)/apolipoprotein A-I (A-I) ratio was studied in fourteen healthy students, fifteen male habitual drinkers, five male patients with chronic hepatitis (CH) and seven controls. HDL-Ch/A-I ratio in male students, female students, male drinkers, CH and control were 0.36 +/- 0.029, 0.39 +/- 0.03, 0.41 +/- 0.065, 0.40 +/- 0.02, and 0.36 +/- 0.039, respectively. Elevation of HDL-Ch/A-I ratio in female students, male drinkers and CH were statistically significant compared with control, while there was no significant change in HDL-Ch or A-I in female students but the elevations of both in male drinkers or the reduction of A-I in CH. Positive correlations were found between HDL-Ch/A-I ratio and HDL2-Ch, and HDL2-Ch/HDL3-Ch ratio in students and CH. The elevation of HDL-Ch/A-I ratio in CH appeared to be related to the reduction of HDL3-Ch. It is suggested that HDL-Ch/A-I ratio could indicate HDL2-Ch/HDL3-Ch ratio and is useful parameter for analysis of HDL metabolism.

Adult↗

Advanced carcinoma of the stomach treated with definitive proton therapy.

We report the case of a 72-yr-old man who suffered from severe chronic emphysema with poor pulmonary function, and who had advanced cancer of the stomach. Proton beam radiotherapy was applied to the lesion, since surgery was contraindicated. The total dose to the stomach lesion was 61 Gy in 7 wk. The tumor on the stomach regressed, with flattening of the round wall of the lesion. The reactive changes of the proton beam radiotherapy, based on the histopathological examination, revealed extensive tumor necrosis and sparing of vital architecture of normal tissue around the irradiated tumor tissue. Only small clusters of vital or devitalized tumor cells with less than approximately 5% of the whole tumor tissue remained after treatment. We suggest that a high dose of radiation delivered by well-defined proton field could result in an improved therapeutic outcome without undue risk of injury to normal tissue.

Adenocarcinoma↗