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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 325 records · Page 18Linked to original sources
PubMed1999

Effect of photodynamic therapy using 5-aminolevulinic acid on 4-nitroquinoline-1-oxide-induced premalignant and malignant lesions of mouse tongue.

A new photosensitizing agent 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) has been demonstrated as a useful method for treatment of superficial neoplastic lesions. The aim of this study was to determine the effects of topically and systemically ALA-based PDT in neoplastic lesions of the oral cavity. Premalignant and malignant lesions of mouse tongue induced by 4-nitroquinoline-l-oxide (4NQO) were used in this study. At 1, 2 and 3 h after topical application of ALA or 3 h after systemic administration of ALA (250 or 1000 mg/kg), the lesions were irradiated with Nd: YAG dye laser at 630 nm (200 J/cm2). Both premalignant and early malignant lesions showed complete response to systemically ALA-based PDT. In an invasive nodular malignant lesion, however, only the superficial portion was affected. There was no apparent difference in the PDT effect between 250 and 1000 mg/kg doses of ALA. In contrast, topically ALA-based PDT had virtually no effect on most lesions. It was concluded that systemically ALA-based PDT is a useful method for treating premalignant and early malignant lesions in the oral cavity, while topically ALA-based PDT using this preparation may be unsuitable for treatment of oral lesions.

4-Nitroquinoline-1-oxide↗
PubMed1999

Cell kinetics of mouse tumour subjected to photodynamic therapy--evaluation by proliferating cell nuclear antigen immunohistochemistry.

Tumour reaction and tumour cell kinetics in mouse NR-S1 carcinoma subjected to photodynamic therapy (PDT) were evaluated by percentage of necrotic area as well as by proliferating cell nuclear antigen (PCNA) immunohistochemistry, and an effective PDT fractionation interval was proposed. PDT was carried out in mouse NR-S1 carcinomas using a photosensitizer (haematoporphyrin oligomers: 20 mg kg body weight) and pulsed Nd:YAG dye laser. The percentages of tumour necrotic area and PCNA labelling indices (LIs) in the tumours were assessed at intervals of 0, 0.5, 5, 2.5, 6, 24, 48, and 72 h after PDT. It was demonstrated that maximum damage and repopulation of the tumour cells emerge at 24 and 48 h, respectively, following PDT, suggesting that subsequent light treatment should be performed within 24 h to enhance the therapeutic effect of PDT.

Animals↗
PubMed1999

Ultrastructural characteristics of TSH-producing adenomas with special reference to its close similarity to BFA-treated pituitary adenoma cells.

Two of 420 patients with pituitary adenoma who underwent operation from 1989 to 1997 had thyroid stimulating hormone (TSH) producing adenoma. We investigated these TSH cell adenomas with immunohistochemical and ultrastructural methods and compared their ultrastructural features with brefeldin A (BFA, 0.5 mg/ml) treated pituitary adenoma cells. BFA-treated pituitary adenomas include a prolactin (PRL) cell adenoma, a growth hormone (GH) cell adenoma, an adrenocorticotropic hormone (ACTH) cell adenoma, a gonadotroph adenoma, and a plurihormonal adenoma. Immunohistochemical staining disclosed that one of the TSH cell adenomas produced only TSH-beta and that another produces both TSH-beta and FSH-beta. Ultrastructural analysis showed the abundance of oval-shaped dilated rough endoplasmic reticulum (rER). Within the dilated rER, the mistlike deposit or deposit along the inner margin of the rER membrane was observed. On the other hand, BFA-treated cultured pituitary adenoma cells showed the opening of the cavity of the rER cisterna and they enlarged to an oval form with time and revealed an accumulation of electron-dense deposits within the dilated rER. These ultrastructural similarities between TSH cell adenoma and BFA-treated pituitary adenoma cells indicate the functional disturbances in the secretory passage through the Golgi apparatus in TSH cell adenoma cells.

Adenoma↗
PubMed1999

Bloom's syndrome gene suppresses premature ageing caused by Sgs1 deficiency in yeast.

BACKGROUND: Bloom's syndrome (BS) is an autosomal recessive disorder causing short stature, immunodeficiency, and an increased risk of cancer. Increased rates of sister chromatid exchange and chromosomal aberration have been observed in cells having defects in the BLM gene. Among five kinds of human RecQ helicases cloned, the mutations in WRN and RecQL4 have been known as the causes of premature ageing. Little is, however, known about the function of BLM helicase in ageing. RESULTS: We show that human BLM, but not WRN can prevent the premature ageing and the increased homologous recombination at the rDNA loci caused by sgs1 mutation. Unexpectedly, the levels of ERCs (extrachromosomal rDNA circles), the products of homologous recombination, formed in 7-generation cells of the wild-type or the sgs1:BLM strain were comparable with those of the sgs1 or the sgs1:WRN age-matched-old cells. CONCLUSION: These results imply that BLM helicase may have an important role in human ageing. In addition, these data suggest that the accumulated ERCs per se may be not the cause of premature ageing in yeast, inconsistent with the model proposed by Sinclair & Guarente. We discuss a new model, which explains how Sgs1 or BLM helicase suppresses premature ageing in yeast.

Aging, Premature↗
PubMed1999

Transcriptional regulation of fatty acid synthase gene by insulin/glucose, polyunsaturated fatty acid and leptin in hepatocytes and adipocytes in normal and genetically obese rats.

Transcriptional regulation of the fatty acid synthase (FAS) gene by insulin/glucose, polyunsaturated fatty acids and leptin was investigated in hepatocytes and adipocytes of Wistar fatty rats and their lean littermates. The sequence spanning nucleotides -57 to -35 of FAS gene, which is responsive to insulin/glucose stimulation [Fukuda, H., Iritani, N. & Noguchi, T. (1997) FEBS Lett. 406, 243-248], was linked to a reporter gene containing a heterologous promoter and transfected into rat hepatocytes or adipocytes. The activity of the reporter, chloramphenicol acetyltransferase, in the presence of glucose alone was similar in the primary cultured cells from the lean and obese rats. In the presence of insulin/glucose, however, chloramphenicol acetyltransferase activity was markedly increased in hepatocytes of lean rats, but was not significantly increased in those of obese rats. The stimulation by insulin/glucose was reduced in arachidonic acid-treated cells of lean rats. Similarly, the stimulation by insulin/glucose was reduced in leptin-treated cells and in cells from lean rats containing an expression vector encoding leptin. However, neither polyunsaturated fatty acids nor leptin-treated cells from obese rats responded to insulin-stimulation. The same effects were observed at endogenous FAS mRNA and enzyme levels. Similar results were seen in adipocytes, although the stimulation and suppression were much smaller than in hepatocytes. The insulin-binding capacities of the receptors of liver and adipose tissue were reduced in the presence of leptin or polyunsaturated fatty acids. Leptin and polyunsaturated fatty acids appeared to suppress the insulin stimulation of FAS transcription by reducing the insulin-binding capacities of receptors. Leptin converged on the insulin/glucose response element of FAS gene and suppressed the transcription.

Adipocytes↗
PubMed1999

Prenatal and postnatal histories of very low birthweight infants who developed hepatoblastoma.

BACKGROUND: Hepatoblastoma in children of very low birthweight (< 1500 g) is increasing in Japan and this has suggested the presence of either a genetic or environmental etiology. This study was aimed at revealing common prenatal and postnatal histories, including family history of hepatoblastomas in children of very low birthweight. METHODS AND RESULTS: The medical records of 15 patients, nine boys and six girls, were reviewed. The patients were diagnosed at the age of 6-77 months (median 16 months). Their birthweight ranged from 560 to 1380 g (median 826 g) and the gestational age was 23-33 weeks (median 25 weeks). No parents were exposed to any occupational risk factors and there were no characteristic features in the parents' history or the maternal reproductive history, although one patient was born to a mother who had taken a contraceptive before she got pregnant with the patient as a result of in vitro fertilization. A ventricular septal defect and an atresia of the external auditory canal were congenital anomalies seen in the patients, but congenital anomalies associated with hepatoblastoma were not seen. Early postnatal illnesses included respiratory distress syndrome in six patients, symptomatic patent ductus arteriosus in three patients, chronic lung disease in seven patients, cytomegalovirus hepatitis in one patient and cholelithiasis in one patient. Oxygen therapy was given to 13 patients for a period of 4-508 days (median 112 days) and lengths of oxygen therapy and assisted ventilation were significantly longer in patients with a stage IIIB or IV tumor than those with a stage II or IIIA tumor (P = 0.0040 and 0.0190, respectively). Furosemide was used in 13 patients for a period of 6-460 days (median 88 days) and the length of the treatment was also significantly longer in patients with advanced tumors (P = 0.0420). Among the patients at 23-25 weeks of gestation, these treatments tended to be longer in patients with a stage IIIB or IV tumor than those with a stage II or IIIA tumor. CONCLUSIONS: These results suggest the presence of an environmental etiology, rather than a genetic one, which is responsible for the development of hepatoblastoma in children of very low birthweight. Close monitoring of the children after being discharged from the neonatal intensive care unit is essential and a case-control study is necessary to identify risk factors for hepatoblastoma in children of very low birthweight.

Child↗
PubMed1999

Functional circuitry for the induction of prolonged excitation in the rat spinal dorsal horn.

The neuronal circuitry through which prolonged excitation is generated in the spinal dorsal horn was investigated using optical imaging of neuronal excitation in transverse slices of rat spinal cords. It is known that tetanic stimulation (20 Hz for 1 s) of the dorsal root that activates both A and C primary afferent fibres elicits slow intrinsic optical signals (IOS) in the dorsal horn, seen most intensely in the substantia gelatinosa (SG), lamina II, and that IOS expresses in part the slow synaptic response recorded intracellularly in dorsal horn neurons. We here report that the slow IOS within the SG were completely abolished after an incision was made at the border between the SG and the deeper laminae, but not after an incision within the deeper dorsal horn of the laminae III-V. The result demonstrates directly that, in order to generate prolonged excitation in the SG, the neuronal elements in the deeper dorsal horn must be intact. Thus, the afferent information might be received first by the deeper elements and then transmitted to the SG region, and/or collaboration between the SG and deeper elements is necessary to maintain prolonged excitation in the SG.

Animals↗
PubMed1999

Competitive polymerase chain reaction for the determination of N-myc amplification in neuroblastoma: report of clinical cases.

If an unfavorable prognosis is suspected in neuroblastoma, decision on a treatment protocol should be based on the N-myc copy number (12). We already demonstrated that the newly developed competitive polymerase chain reaction (competitive PCR) is a promising method for the determination of the N-myc copy number (6), and have started to use this competitive PCR procedure in neuroblastoma patients, together with fine-needle biopsy in selected cases. Seven children were studied. In one infant of 5 months of age whose tumor was diagnosed before undergoing mass screening for neuroblastoma, the competitive PCR procedure was performed with a fine-needle biopsy, and after obtaining a negative report on N-myc amplification within 48 hours, a regular protocol of treatment could be started without delay. We report that competitive PCR is a rapid and accurate method for the determination of the N-myc copy number, requiring only a small amount of material, and anticipate that competitive PCR will become the procedure of choice for the determination of N-myc copy number in neuroblastoma.

Adrenal Gland Neoplasms↗
PubMed1999

Neurosurgical simulation and navigation with three-dimensional computer graphics.

We developed a pre-operative simulation and intra-operative navigation system with three-dimensional computer graphics (3D-CG). Because the 3D-CG created by the present system enables visualization of lesions via semitransparent imaging of the scalp surface and brain, the expected operative field could be visualized on the computer display pre-operatively. We used two different configurative navigators. One is assembled by an arciform arm and a laser pointer. The arciform arm consists of 3 joints mounted with rotary encoders forming an iso-center system. The distal end of the arm has a laser pointer, which has a CCD for measurement of the distance between the outlet of the laser beam, and the position illuminated by the laser pointer. Using this navigator, surgeons could accurately estimate the trajectory to the target lesion, and the boundaries of the lesion. Because the other navigator has six degrees of freedom and an interchangeable probe shaped like a bayonet on its tip, it can be used in deep structures through narrow openings. Our system proved efficient and yielded an unobstructed view of deep structures during microscopic neurosurgical procedures.

Computer Graphics↗
PubMed1999

Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26.

Moyamoya disease is characterized by bilateral stenosis and/or occlusion of the terminal portion of the internal carotid artery. Moyamoya disease is prevalent among patients <10 years of age. Although most cases appear to be sporadic, approximately 10% occur as familial cases. The incidence of familial cases has been increasing because noninvasive diagnostic equipment, such as magnetic-resonance imaging and magnetic-resonance angiography, can detect the disease in almost all affected patients, including asymptomatic patients, during screening studies. In this study, we performed a total genome search to identify the location of a familial moyamoya disease gene in 16 families, assuming an unknown mode of inheritance. A linkage was found between the disease and markers located at 3p24.2-26. A maximum NPL score of 3.46 was obtained with marker D3S3050. This is the first genetic locus found to be involved in the molecular pathogenesis of familial moyamoya disease.

Base Sequence↗
PubMed1999

Primary cultures of human endothelial cells are susceptible to low doses of Shiga toxins and undergo apoptosis.

Various endothelial cells, with the exception of those from human microvasculatures, have been known to resist Shiga toxins (Stxs) in vitro. However, freshly prepared primary cultures of human endothelial cells from the umbilical vein and artery and the saphenous vein were shown to be killed by a very low dose of Stxs. This cytotoxicity of Stxs involves apoptosis, which seems to be caused by a mechanism distinct from the well-known action of Stxs to inhibit protein synthesis, since the blockade of protein synthesis by cycloheximide could not induce apoptosis or enhance the effect of Stxs. Passaged human endothelial cells have been found to be highly resistant to Stxs, which is consistent with previous reports, and not to show any evidence of apoptosis even when they are killed by a high dose of Stxs.

Apoptosis↗
PubMed1999

Escherichia coli mutM suppresses illegitimate recombination induced by oxidative stress.

DNA damage by oxidative stress is one of the causes of mutagenesis. However, whether or not DNA damage induces illegitimate recombination has not been determined. To study the effect of oxidative stress on illegitimate recombination, we examined the frequency of lambdabio transducing phage in the presence of hydrogen peroxide and found that this reagent enhances illegitimate recombination. To clarify the types of illegitimate recombination, we examined the effect of mutations in mutM and related genes on the process. The frequency of lambdabio transducing phage was 5- to 12-fold higher in the mutM mutant than in the wild type, while the frequency in the mutY and mutT mutants was comparable to that of the wild type. Because 7,8-dihydro-8-oxoguanine (8-oxoG) and formamido pyrimidine (Fapy) lesions can be removed from DNA by MutM protein, these lesions are thought to induce illegitimate recombination. Analysis of recombination junctions showed that the recombination at Hotspot I accounts for 22 or 4% of total lambdabio transducing phages in the wild type or in the mutM mutant, respectively. The preferential increase of recombination at nonhotspot sites with hydrogen peroxide in the mutM mutant was discussed on the basis of a new model, in which 8-oxoG and/or Fapy residues may introduce double-strand breaks into DNA.

Bacteriophage lambda↗
PubMed1999

Local-regional control by conventional radiotherapy according to tumor volume in patients with squamous cell carcinoma of the pharyngolarynx.

BACKGROUND: To estimate the effect of tumor volume on local-regional control of pharyngolaryngeal cancer by radiotherapy (RT). METHODS: Definitive RT for 48 patients with squamous cell carcinoma of the lateral wall of the oropharynx, pyriform sinus and supraglottic larynx was reviewed. Tumor volume was estimated from computed tomography and it was expressed as the diameter of a sphere the volume of which is equal to the primary tumor (Td) and sum of the volumes of metastatic adenopathies (Nd). All patients received > or =60 Gy (median 66 Gy) to the gross tumor by conventional fractionation with or without chemotherapy. RESULTS: A median period of follow-up for survivors was 32.7 months (range, 12.4-68.6). The 2 year local control rate for T1/2 (n = 30) and T3/4 (n = 18) patients was 72 and 65%, respectively (P= 0.966), however, the rates for Td < 4 cm tumors (n = 37) and Td > or = 4 cm tumors (n = 11) were significantly different (80% vs 27%, P < 0.001). The 2 year regional control rates for Nd < 3 cm lesions (n = 29) and Nd > or = 3 cm (n = 19) lesions were 85 and 42%, respectively (P < 0.001). The 2 year ultimate regional control rates for N2/3 disease with Nd < 4 cm (n = 11) and Nd > or = 4 cm (n = 11) were 100 and 42%, respectively (P = 0.004). CONCLUSIONS: Conventional radiotherapy may allow organ preservation and ultimate local control in patients with Td < 4 cm and Nd < 4 cm disease, but larger volume tumors should be considered candidates for the most intensive chemoradiotherapy.

Adult↗
PubMed1999

National average for the process of radiation therapy in Japan by Patterns of Care Study.

BACKGROUND: A nationwide effort is in progress to establish the actual state of radiotherapy and its quality assurance (QA) in Japan by using the Patterns of Care Study (PCS). In this study, national averages are calculated with a limited number of patients. A calculation program for national averages was prepared and applied to the radiotherapeutic processes used for esophageal cancer patients entered in the PCS. METHODS: The calculation program for national averages, which were revised on the basis of differences between individual facilities and institutional strata, was developed in accordance with Sedransk's equation for the original PCS in the USA. National averages for several aspects concerning the sampled patients who had esophageal cancer between 1992 and 1994 were calculated with these procedures. Data for facilities and stratification of institution were simulated from a national structure survey of radiation oncology in 1990. RESULTS: Values of the national average by Sedransk's equation were different from those of the simple sample average. There were significant differences in radiotherapeutic processes among stratification of institutions. For esophageal cancer, national averages were 0.129 for applications of endoscopic ultrasound, 0.599 for 'all fields treated each day' and 0.088 for application of brachytherapy. CONCLUSION: National averages for radiotherapy could be calculated. The values obtained in this PCS will be a useful measure for future QA in radiation oncology and in other specialties in Japan.

Esophageal Neoplasms↗
PubMed1999

Analysis of 57 nonagenarian cancer patients treated by radical radiotherapy: a survey of eight institutions.

BACKGROUND: As the human society grows more aged, it is considered important to elucidate factors essential in applying radical radiotherapy (RT) to the elderly, with ages as high as 90 years and greater. METHODS: A retrospective survey was conducted for patients 90 years of age or older who received radiotherapy with radical intent in eight leading institutions in Japan from 1990 through 1995. RESULTS: Fifty-seven nonagenarian patients were studied. Their ages ranged up to 98 (median 91) and there was a strong female preponderance (M/F: 16/41). The distribution by site was as follows: head and neck, 16; skin and adnexae, 11; uterine cervix, 7; esophagus, 6. The prevailing histopathological diagnosis was squamous cell carcinoma (34), followed by adenocarcinomas (8). The highest age at RT was 98 years [female, skin cancer, died of senility 2.5 years after treatment, with no evidence of disease (NED)] and the longest survivor is 102 years old (female, glottic cancer T2, age at RT 93, alive NED for 8 years, uses wheel-chair). The rate of completion of treatment was 75% (43/57), if the treatment field was limited to the gross primary tumor volume only and if the cumulative dose was above 80% of the tolerable adult dose. Familial escort was necessary for most of the patients in completing the day-to-day RT. CONCLUSION: Radiotherapy is feasible with radical intent even in the elderly, if the treatment field is limited to the gross primary tumor volume only, if the cumulative dose is above 80% of the tolerable adult dose and if familial support is adequate.

Aged↗
PubMed1999

Preliminary results of pelvic autonomic nerve-preserving surgery combined with intraoperative and postoperative radiation therapy for patients with low rectal cancer.

BACKGROUND: In Japan, lateral lymphadenectomy was widely performed for patients with stage II-III rectal tumors because it was thought to contribute to good local control, but the pelvic autonomic nerves were thus sacrificed. Although autonomic nerve-sparing surgery with lateral lymph node dissection has been tried from around 1987, the type of nerve sparing varied and the indications were not established. To examine the possibility of expanding the indications for total pelvic autonomic nerve preservation for patients with low rectal cancer, we conducted a pilot study. METHODS: Between 1993 and 1997, a total of 50 patients with low rectal cancer underwent pelvic autonomic nerve preservation with lateral lymphadenectomy of both sides and intraoperative radiation therapy followed by postoperative radiation therapy. RESULTS: The median follow-up period for surviving patients was 41 months. The 3-year local control rates for all patients, with stage I-II and stage III tumors were 88% (95% confidence interval, 78-97%), 97% (90-100%) and 73% (52-94%), respectively. The site of local recurrences was not near or within the preserved plexus. CONCLUSIONS: The preliminary results showed good local control rate for patients with stage I-II tumors. For patients with stage III tumors, the local control rate was unsatisfactory, but nerve sparing was not the cause of local recurrence. Further investigation of function-preserving surgery without decreasing curability is needed.

Adult↗