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Biomedical subjects

K Sasai

Publications and source records attributed to K Sasai.

At least 55 records · Page 3Linked to original sources

Long-term results of radiation therapy for pituitary adenoma.

PURPOSE: Local control for pituitary adenomas treated with external beam radiation therapy was retrospectively analyzed to evaluate the efficacy of radiation. MATERIALS AND METHODS: Thirty-eight patients treated with radiation therapy between 1979 and 1994 were analyzed. The median age was 46. Nineteen newly diagnosed tumors were treated with surgery and radiation therapy, while the others were recurrent cases. Twenty-two tumors were non-functioning, while 10 produced growth hormone (GH) and three each were prolactin-, and adrenocorticotropic hormone (ACTH)-producing tumors. The median-radiation dose was 50 Gy in 25 fractions. RESULTS: Non-functioning adenomas and prolactin-producing adenomas were completely controlled, judging from the absence of tumor progression on neuroimaging studies and clinical symptoms, and normalization of the serum prolactin level (< 25 ng/ml). On the other hand, local control was obtained in only one of the 3 patients with ACTH-producing adenomas, and the control rate at 10 years was only 46% for GH-producing adenomas. Panhypopituitarism developed in 35% of the patients after radiation therapy. No other serious complications were noted. CONCLUSION: Non-functioning pituitary adenomas and prolactin-producing adenomas were well controlled with external radiation therapy combined with surgery. However, dose escalation might be necessary to control GH-or ACTH-producing tumors. It is important to replace corticosteroid hormone and thyroid hormone in many patients.

Adolescent↗

Kinetic basis for the donor nucleotide-sugar specificity of beta1, 4-N-acetylglucosaminyltransferase III.

The kinetic basis of the donor substrate specificity of beta1, 4-N-acetylglucosaminyltransferase III (GnT-III) was investigated using a purified recombinant enzyme. The enzyme also transfers GalNAc and Glc moieties from their respective UDP-sugars to an acceptor at rates of 0.1-0.2% of that for GlcNAc, but Gal is not transferred at a detectable rate. Kinetic analyses revealed that these inefficient transfers, which are associated with the specificity of the enzyme, are due to the much lower V(max) values, whereas the K(m) values for UDP-GalNAc and UDP-Glc differ only slightly from that for UDP-GlcNAc. It was also found that various other nucleotide-Glc derivatives bind to the enzyme with comparable affinities to those of UDP-GlcNAc and UDP-Glc, although the derivatives do not serve as glycosyl donors. Thus, GnT-III does not appear to distinguish UDP-GlcNAc from other structurally similar nucleotide-sugars by specific binding in the ground state. These findings suggest that the specificity of GnT-III toward the nucleotide-sugar is determined during the catalytic process. This type of specificity may be efficient in preventing a possible mistransfer when other nucleotide-sugars are present in excess over the true donor.

Acetylgalactosamine↗

Lactobacillus flora in the cloaca and vagina of hens and its inhibitory activity against Salmonella enteritidis in vitro.

Lactobacilli in the cloaca and vagina of 40 normal laying hens were investigated quantitatively and qualitatively, and their ability to inhibit growth of Salmonella enteritidis (SE) was examined using a spot-the-lawn technique. All samples of cloacal contents and half the samples of vaginal mucus were positive for lactobacilli. The means +/- SD of total Lactobacillus counts in the cloaca and those in the vagina were log10 5.5 +/- 1.1 and 2.5 +/- 2.6 cfu/g, respectively. In the cloaca, Lactobacillus acidophilus was isolated from 92.5% of hens, and Lactobacillus salivarius was isolated from 85.0% of hens, whereas Lactobacillus fermentum was isolated from only one hen. In the vagina, L. acidophilus and L. salivarius were isolated from 42.5% of hens. In the inhibition assay in vitro, all strains of Lactobacillus from cloacal contents and vaginal mucus inhibited growth of SE. There was a wide range of the inhibitory activity even in the same species. No difference of the growth inhibition zone was observed between lactobacilli from cloaca and those from vagina. The present study suggested that lactobacilli in the cloaca and vagina of hens might have a protective effect against SE colonization.

Animals↗

Results of breast-conserving therapy for early stage breast cancer: Kyoto University experiences.

This study evaluated the results of breast-conserving therapy (BCT). Nine hundred six patients who underwent BCT at our hospital between November 1987 and February 1998 were analyzed. The mean age was 48 years. According to the Union Internationale Contre le Cancer 1997 classification system, stages 0, I, IIA, IIB, IIIA, and IIIB were 37, 400, 344, 117, 7, and 1, respectively. Radiation therapy consisted of 50 Gy to the ipsilateral whole breast. Boost irradiation of 10 Gy was administered to 186 of 231 patients with close or positive margins. Nearly all patients received adjuvant chemohormonal therapy with tamoxifen and 5-fluorouracil or its derivatives for 2 years. The minimum and median follow-up periods were 18 and 52 months, respectively. The 5-year overall survival, cause-specific survival, local recurrence-free survival, and disease-free survival rates were 97.3%, 98.4%, 98.1%, and 91.5%, respectively. Local recurrence in preserved breast occurred in 20 patients 7 to 86 months after surgery. Multivariate analysis revealed that the most predictive factor for disease-free survival rates and distant failures was the number of pathologically positive lymph nodes (p < 0.0001), and that the factor for local failure was marginal status (p = 0.005). This study demonstrated that BCT was suitable for the treatment of early-stage breast cancer with its reasonable survival rates and acceptable toxicity.

Breast Neoplasms↗

Cervical curvature after laminoplasty for spondylotic myelopathy--involvement of yellow ligament, semispinalis cervicis muscle, and nuchal ligament.

To assess the consequences of cervical laminoplasty on postoperative lordosis, a retrospective radiographic analysis of 31 patients undergoing laminoplasty for spondylotic myelopathy was completed. Special attention was paid to lordotic changes occurring at each level over more than 2 years. Preoperative lordosis remained unchanged with the patients wearing a cervical orthosis 1 week postoperatively. However the lordosis subsequently demonstrated a significant decrease in 87% of patients over an average of 3.1 years. Lordotic alignment at C2-C3 and C6-C7 before surgery significantly decreased in 81% and 58% of patients 1 week postoperatively, and 84% and 81% at last follow up, respectively, while lordotic alignment at other levels pre- and postoperatively did not significantly change. Loss of lordotic alignment was largely attributed to detachment of semispinalis cervicis muscle on C2 and nuchal ligament on C6/C7 with a posterior approach and/or section of yellow ligament at C2-C3.

Adult↗

Enhanced cell killing by overexpression of dominant-negative phosphatidylinositol 3-kinase subunit, Deltap85, following genotoxic stresses.

Phosphatidylinositol 3-kinase (PI3-K) is a heterodimer of a regulatory subunit, p85, and a catalytic subunit, p110. A number of previous reports showed that PI3-K functions in diverse cellular phenomena such as cell proliferation, glucose catabolism, cell adhesion, and vesicle transport. It is also well known that a survival signal from the receptor tyrosine kinases utilizes Akt via PI3-K to protect cells from apoptosis. To examine the role of PI3-K in cellular sensitivity to genotoxic stresses such as cisplatin and ultraviolet (UV), we introduced deletion type p85 (Dp85) into two human glioblastoma cell lines (T98G and A172) and one melanoma cell line (G361). The Deltap85 works in a dominant-negative fashion on PI3-K activity by disrupting its p85 / p110 interaction. In all three transfected cell lines, the overexpression of Deltap85 rendered the cells markedly more sensitive to these DNA-damaging stresses than the cells transfected with the vector alone. Apoptosis was vigorously induced in cells overexpressing Dp85 following the treatment. The present results imply that PI3-K plays a critical role in determining cellular sensitivity to genotoxic stresses in human cancer cells, and that disruption of the p85 / p110 interaction of PI3-K may be a potential molecular target for developing a novel strategy for cancer treatment.

Apoptosis↗

Study of lipid in the ear canal in canine otitis externa with Malassezia pachydermatis.

An epidemiological investigation of 120 canine otitis externa cases in 1,370 dogs was done on the incidence rate, ear pinna shapes, breeds and their relationships. Eighty-five cases (12.6%) in 672 dogs with pendulous ears and 35 cases (5.0%) in 698 dogs with erect ears had otitis externa, and the difference between them was significant (P<0.05). Ninety-five auditory cerumen specimens were cultured for Malassezia pachydermatis (M. pachydermatis) and analyzed for concentrations of major fatty acids. Although rates of cases positive for M. pachydermatis in both ear pinna shapes were almost the same, i.e. 55.2% in the pendulous group and 53.6% in the erect group, the average total fatty acid level of the pendulous ear group was significantly (P<0.05) higher than that in the erect ear group after dismissing extraordinary levels in the Siberian husky. Isolated M. pachydermatis strains were examined for the effects of fatty acid supplementation on their growth. The majority of the strains utilized fatty acids and grew faster in fatty acid supplemented broth. These results suggest that M. pachydermatis, the predominant causative agent of canine otitis externa, prefers the auditory canal of dogs with lipid-rich earwax and grows fast, but growth strongly depends upon the canine breed.

Animals↗

Clinical and pathologic characteristics of lumbar disk herniation in the elderly.

The clinical and pathologic characteristics of lumbar disk herniation in 23 elderly patients (15 men and 8 women) who required surgical treatment were investigated. Average age at surgery was 67.3 years, and average follow-up was 23 months. Preoperatively, the predominant symptom was severe unilateral leg pain, and 13 patients were nonambulatory because of leg pain. Operative treatment included wide laminectomy in 8, hemilaminectomy in 3, fenestration in 10, and osteoplastic laminectomy in 2 patients. Four (17%) patients had disk herniation at the L2-L3 or L3-L4 level. Sequestered herniation with or without migration was observed in 15 (65%) patients. Of 14 sequestered disk fragments examined histologically, 8 (57%) specimens contained cartilaginous or bony end plate with anulus fibrosus or nucleus pulposus. Postoperatively, results were rated as excellent in 11 patients and good in 12; no patient was rated as fair or poor. Severe leg pain affecting activities of daily life is a predominant symptom of disk herniation in the elderly. For patients in whom conservative treatment has failed, operative treatment should be considered. In lumbar disk herniation in the elderly, the incidence of cephalad and lateral herniation is higher than in younger patients. In addition, sequestered and migrated herniations including end plate are frequent.

Activities of Daily Living↗

External iliac artery occlusion in posterior spinal surgery.

STUDY DESIGN: Report of a case of external iliac artery occlusion occurring as a rare complication of lumbar posterior spinal surgery. OBJECTIVE: To clarify the cause of this rare complication and recommend methods for preventing its recurrence. SUMMARY OF BACKGROUND DATA: Several cases of central retinal artery occlusion after posterior spinal surgery have been reported, but there has been no reported case of external iliac artery occlusion after posterior spinal surgery. METHODS: A 65-year-old woman who had a 32-year history of systemic lupus erythematosus underwent posterior decompression and spinal fusion for degenerative scoliosis. She was supported on a Hall frame during the operation. Three hours after surgery, paralysis and sensory impairment of the left leg and cyanosis of the toes of the left foot were noted. The popliteal, dorsalis pedis, and posterior tibial pulses were not palpable. Angiography showed complete occlusion of the external iliac artery, and emergency removal of the thrombus was performed. RESULTS: One year later, neurologic symptoms were absent, and the leg vessels were normal. CONCLUSIONS: Prolonged direct pressure on the inguinal region during posterior spinal surgery on a Hall frame may cause external iliac artery occlusion. Early recognition and adequate treatment can prevent serious sequelae.

Aged↗

Secretion of Salmonella-specific antibodies in the oviducts of hens experimentally infected with Salmonella enteritidis.

The production and secretion of Salmonella enteritidis whole cell antigen-specific antibodies in the oviducts and in the serum of laying hens experimentally infected with Salmonella enteritidis, was analyzed by ELISA. The dynamics of the antibody levels in the oviducts were identical to that in the serum. Subclasses of antibodies (IgA, IgG, and IgM) in the infected hens were found to increase significantly (p < 0.01) compared to those in the control uninfected hens throughout the experiment. IgG and IgM levels in both oviducts and in sera reached to a peak by 14 days post-inoculation, and remained elevated throughout. The secretion of IgA seemed to be transient since the IgA levels increased to a peak 7 days after both primary and secondary inoculations, and declined rapidly. The elevated levels of antibodies were followed by partial clearance of Salmonella organisms from the oviducts. The present results indicate a significant local immune reaction against the Salmonella infection and suggest an association of the local antibodies with the clearance of Salmonella from the oviducts at least partially.

Animals↗

Cytosolic/microsomal redox pathway: a reductive retention mechanism of a PET-oncology tracer, cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (cu-PTSM).

OBJECTIVE: To clarify the retention mechanism of a PET imaging agent Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-62-PTSM) in tumor cells, reductive metabolism of non-radioactive Cu-PTSM in five cultured tumor cell lines, a tumor specimen and non-tumor tissues in vitro was evaluated by electron spin resonance spectrometry (ESR). RESULTS: In the brain, mitochondrial electron transport enzyme reduced Cu-PTSM specifically. On the other hand, Cu-PTSM was not reduced in tumor mitochondria. The mitochondrial electron transport enzyme in tumor cells was not damaged, but NADH was considered to be depleted. In compensation for that, the tumor cells acquired complementary reduction activity in the microsome/cytosol. The reduction was enzymatic and NADH-dependent, possibly similar to the activation mechanism of bioreductive anticancer drugs. CONCLUSION: Cu-PTSM and its derivatives are considered to be used as a marker for microsome/cytosol redox ability in PET oncology, although the physiological role of the redox enzyme system in tumor cells has not been clarified. The change in electron (NADH) flow in tumor cells might be a mechanism supporting aerobic glycolysis in tumor cells.

Animals↗

Systemic chemotherapy with vincristine, cyclophosphamide, doxorubicin and prednisolone following radiotherapy for primary central nervous system lymphoma: a phase II study.

We treated 23 patients with primary central nervous system lymphoma with a protocol of conventional radiation up to 55 +/- 5 Gy followed by 4 to 6 cycles of intravenous doxorubicin (30 mg/m2), vincristine (1 mg/m2) and cyclophosphamide (350 mg/m2), and oral prednisolone (8-30 mg/m2) (VEPA chemotherapy) repeated at 2-week intervals. The median age of the 23 patients was 59 years, and the median World Health Organization performance status score was 2. Seventeen patients received 4 or more courses of the chemotherapy, but 6 received only 1 or 2 courses for various reasons. The median survival time for all 23 patients was 25.5 months and their 5-year survival rate was 23%. These values were 34 months and 32%, respectively, for the 17 patients who received 4-6 courses of chemotherapy. After treatment, decline in performance status unaccompanied with tumor recurrence was observed in 44% of the patients; the incidence was apparently higher in older than in younger patients. The survival results obtained with this combined radiochemotherapy regimen appear to be better than those reported in most previous studies of patients treated with radiation alone. Post-irradiation VEPA chemotherapy appears to be worthy of further evaluation.

Adult↗

Salvage radiation therapy for intracranial germinoma recurring after primary chemotherapy.

Systemic chemotherapy has been increasingly used in the primary treatment of intracranial germinoma. However, the recurrence rate seems to be very high after treatment with chemotherapy alone. We used radiation to treat 5 patients harboring intracranial germinoma that recurred following primary chemotherapy. They had received systemic chemotherapy (4 with cisplatin plus etoposide and 1 with adriamycin, vincristine, cyclophosphamide, prednisolone, and cisplatin) 7-24 months before referral. All patients were treated with conventional radiotherapy directed to the primary tumor site or the craniospinal axis with a dose to the primary site ranging from 39.6 to 47.0 Gy (mean, 42.6 Gy). Response to radiation of all the recurrent tumors was good and all tumors disappeared on diagnostic imaging below the dose of 24 Gy. All patients are alive without further recurrence at 61-129 months after salvage radiotherapy. Germinomas recurring after primary chemotherapy do not seem to have acquired cross resistance to radiotherapy. They can usually be cured by standard radiation therapy with 40-47 Gy.

Adolescent↗

Suppression of experimental corneal angiogenesis by focal X-ray irradiation.

PURPOSE: To investigate the effect of focal X-ray irradiation on experimental corneal angiogenesis in the rabbit. METHODS: A gelatin hydrogel sheet impregnated with basic fibroblast growth factor was implanted into the corneal stroma of rabbits; this induced corneal angiogenesis. After the first sign of corneal angiogenesis was noted, the corneal region was irradiated with a dose of 10 Gy or 20 Gy. The control rabbits received no irradiation. The eyes were examined by slitlamp biomicroscopy and photographed, over a period of 28 days. The maximum length and total surface area of corneal angiogenesis were quantified by computerized image analysis. RESULTS: Corneal angiogenesis was noted on day 3 following implantation of the hydrogel sheet. In the rabbits irradiated with 10 Gy, the maximum length and total surface area of corneal angiogenesis were both significantly lower on day 4 and 7 following irradiation, compared to the respective measurement in the controls. In the rabbits irradiated with 20 Gy, the maximum length and total surface area of corneal angiogenesis were significantly lower between days 4 and 21, and between days 4 and 14, respectively, compared to the respective measurement in the controls. CONCLUSIONS: Focal X-ray irradiation to the corneal region suppressed corneal angiogenesis in a dose-dependent manner. Focal X-ray irradiation may be beneficial in treating ocular angiogenesis.

Animals↗

Tumor response and patterns of failure following intraoperative radiotherapy for unresectable pancreatic cancer--evaluation by computed tomography.

Tumor response and patterns of failure following intraoperative radiotherapy (IORT) of 42 patients with unresectable pancreatic cancers were evaluated by computed tomography (CT). At the time of maximum tumor regression, the tumor response rate following IORT was 52%, with three tumors showing CR. The median time of maximum tumor regression was 3 months after IORT. When tumor response was evaluated within 2 months of IORT, no significant difference in survival rate between responders and non-responders was noted. However, when tumor response was evaluated 3-6 months after IORT, the responders showed a significantly better survival rate than the non-responders. Local tumor recurrence, liver metastasis, and peritoneal dissemination were major causes of failure after IORT for unresectable pancreatic cancers. In addition, the median time of detection of these findings by CT was 2-3 months after IORT. Thus, our results indicate that CT performed 3-4 months after IORT is most important for predicting clinical outcome.

Adenocarcinoma↗

A significant correlation between clonogenic radiosensitivity and the simultaneous assessment of micronucleus and apoptotic cell frequencies.

PURPOSE: To study the relationship between clonogenic radiosensitivity and a simultaneous assessment of the percentages of radiation-induced micronuclei (MN) and apoptotic cells. MATERIALS AND METHODS: Five mammalian cell lines were studied. Following irradiation, measurements were made of the percentages of MN, apoptotic cells and floating cells. Each factor was compared, both alone and as the simple sum of the factors, with cell survival. The factors were also evaluated using a multiple linear regression analysis. RESULTS: The simple sum of the MN and apoptotic cell percentages, the sum of the MN and floating cell percentages, and the sum of all three factors correlated with cell survival. However, the multiple linear regression analysis was the best method of predicting cell survival. CONCLUSIONS: These results suggest the usefulness of the simultaneous assessment of the MN frequency and the detection of floating cells in culture medium or apoptotic cells among attached cells to predict cellular intrinsic radiosensitivity. In order to predict cell survival after irradiation from these factors, the use of multivariate analyses is more useful than simple summation.

Animals↗

Clinical results of transcatheter arterial infusion for uterine cervical cancer.

The effects of transcatheter intraarterial infusion of anticancer drugs on the prognosis of cervical cancer were retrospectively studied. Two or three sessions of transcatheter arterial infusion therapy were performed for 68 patients with primary uterine cervical cancer. The number of patients with stage I, II, III, or IV disease were 13, 22, 24, and 9, respectively. Patients with squamous cell carcinoma comprised 3, 17, 17, and 5 of the respective groups, and the patients with stage I and II disease had either adenocarcinoma or adenosquamous carcinoma, or bulky tumor (>4 cm). The drugs infused were cisplatin (60-70 mg/m2), doxorubicin hydrochloride (30-40 mg/m2), mitomycin (15 mg/m2), and 5-fluorouracil (500 mg/body). They were infused via the bilateral internal iliac arteries. Fifty-eight of the 68 patients (85%) received a radical hysterectomy after transcatheter arterial infusion: 12 of 13 with stage I disease, 21 of 22 with stage II disease, 20 of 24 with stage III disease, and five of nine with stage IV disease. Two patients with stage III disease received radical radiotherapy. The other eight patients (one with stage I disease, one with stage II disease, two with stage III disease, and four with stage IV disease) did not receive an operation after transcatheter arterial infusion because they had distant metastases at the time of operation. Thirty-two of 58 patients (56%) received postoperative radiotherapy. The complete histologic response rates (no active cancer cells) after transcatheter arterial infusion were: 2 of 12 patients with stage I disease, 3 of 21 patients with stage II disease, 5 of 20 patients with stage III disease, and one of five patients with stage IV disease. Tumors with squamous cell carcinoma disappeared at a significantly better rate (10/36, 28%) than did tumors with adenocarcinoma or adenosquamous cell carcinoma (1/22, 5%; p < 0.05). The overall 5-year survival rates of the patients with stages I, II, and III disease were 92.3%, 62.2%, and 71%, respectively. The 5-year survival rates of the patients who underwent surgery with stage I, II, and III disease were 100%, 66.3%, and 71.5%, respectively. Leukocytopenia and thrombocytopenia occurred as an acute complication in 75% and 79% of the patients, respectively. As a late complication, ileus occurred in 7%. Transcatheter arterial infusion may improve the prognosis of patients with cervical cancer without increasing the incidence of late complications.

Antineoplastic Combined Chemotherapy Protocols↗

Detection of hypoxic cells in murine tumors using the comet assay: comparison with a conventional radiobiological assay.

The comet (single-cell electrophoresis) assay has been developed as a method for measuring DNA damage in single cells after irradiation. We have developed our own methods and image analysis system for the comet assay to identify hypoxic fractions. In vitro, we tested our system using a cultured tumor cell line (SCCVII). In vivo, we compared the hypoxic fractions detected by this assay with those determined by the in vivo-in vitro clonogenic assay using two rodent tumors (SCCVII/ C3H, EMT6/KU/balb/c), which exhibit different types of hypoxia: acute and chronic. In vitro, our method could differentiate hypoxic cells from oxic cells, using the parameter of tail moment. In vivo, there were good correlations between the hypoxic fractions determined by the comet assay and by the clonogenic assay, in SCCVII/C3H (r=0.85) and in EMT6/KU/balb/c (r=0.75) tumors. By comparison of the two methods in chronically hypoxic and acutely hypoxic tumors, we further confirmed that the comet assay is clinically useful for estimating hypoxic fractions of solid tumors.

Animals↗