The authors describe acute deterioration in facial and acoustic neuropathies following radiosurgery for acoustic neuromas. In May 1995, a 26-year-old man, who had no evidence of neurofibromatosis Type 2, was treated with gamma knife radiosurgery (GKS; maximum dose 20 Gy and margin dose 14 Gy) for a right-sided intracanalicular acoustic tumor. Two days after the treatment, he developed headache, vomiting, right-sided facial weakness, tinnitus, and right hearing loss. There was a deterioration of facial nerve function and hearing function from pretreatment values. The facial function worsened from House-Brackmann Grade 1 to 3. Hearing deteriorated from Grade 1 to 5. Magnetic resonance (MR) images, obtained at the same time revealed an obvious decrease in contrast enhancement of the tumor without any change in tumor size or peritumoral edema. Facial nerve function improved gradually and increased to House-Brackmann Grade 2 by 8 months post-GKS. The tumor has been unchanged in size for 5 years, and facial nerve function has also been maintained at Grade 2 with unchanged deafness. This is the first detailed report of immediate facial neuropathy after GKS for acoustic neuroma and MR imaging revealing early possibly toxic changes. Potential explanations for this phenomenon are presented.

PURPOSE:The aim of this study was to solve anisotropy in the dose distributions from rotational conformal radiotherapy (RCRT) by using a C-arm-mounted accelerator. MATERIALS AND METHODS:The linac head was designed to move along the C-arm with a maximum angle of 60 degrees (from a vertical position toward the gantry). Simultaneous rotation of the gantry creates a dynamic conical irradiation technique. Dynamic conical conformal radiation therapy (Dyconic CRT) was developed by combining the technique with continuous motion of a multileaf collimator. Dose distributions were measured in phantoms using film densitometry and compared with conventional RCRT. Dose distributions in actual radiation therapy patients are also presented. RESULTS:Dyconic CRT enabled the precise delivery of noncoplanar beams without rotating the table. The measurements showed that three-dimensionally isotropic dose falloff was achieved with Dyconic CRT. Dose inhomogeneity in the sagittal direction with Dyconic CRT was compensated for by use of wedge filters. CONCLUSIONS:The drawbacks of the dose distributions produced by RCRT were overcome with the use of Dyconic CRT.

頭頸部は複雑な形態をしているため, 単純な照射法では線量が不均一になりやすい。また, critical organ に制限されて思うような線量分布が得られないことも多い。当施設では, 比較的簡単な方法で線量分布の改善を試みているので, 報告する。頭頸部の広い範囲に対する照射によく用いられる左右対向2門照射では, 上下や前後方向に線量の不均一性が避けられず, 平均22%, 10.8Gyの差が生じていた。左右に前方からの照射を加え, wedge filter を用いることで, その不均一性を11.6%, 5.5Gyまで減少可能であった。前方照射野で耳下腺を spare することにより, 耳下腺線量の低下も可能であった。また, C-arm型ライナックを用いた3次元原体照射を用いることにより, ビームの入射方向の自由度が増し, critical organ を避けながら target に比較的均一な高線量を照射することが可能となった。

Treatment of giant cell tumors (GCT) especially in the vertebrae remains controversial. With multidisciplinary treatments, their results are still insufficient. Moreover, GCT shows the potential for malignant transformation and metastasis, additional options such as adjuvant medication must be considered. We report favorable results in three consecutive cases diagnosed with GCT of the spine which were treated with radiotherapy and bisphosphonate (BP) as a new treatment option, and present a review of the literature and a comparison with these case reports.

Several lines of evidence indicate that transcriptional activation is coupled with DNA replication initiation, but the nature of initiation of DNA replication in mammalian cells is unclear. Polyoma virus replicon is an excellent system to analyze the initiation of DNA replication in murine cells because its replication requires an enhancer, and all components of replication machinery, except for DNA helicase large T antigen, are supplied by host cells. This system was used to examine the role of signal transducer and activator of transcription (STAT5) in replication initiation of polyoma replicon in the mouse lymphoid cell line BA/F3. The plasmid with tandem repeats of consensus STAT5 binding sites followed by polyoma replication origin was replicated by stimulation with human granulocyte-macrophage colony-stimulating factor (hGM-CSF) in the presence of polyoma large T antigen in BA/F3 cells. Mutation analysis of the hGM-CSF receptor beta subunit revealed that only the box1 region is essential, and the C-terminal tyrosine residues are dispensable for the activity. Addition of the tyrosine kinase inhibitor genistein suppressed this replication without affecting transcriptional activation of STAT5. Because deletion analysis of STAT5 indicates the importance of the C-terminal transcriptional activation domain of STAT5 for the initiation of replication, the role of this region in the activation of replication was examined with a GAL4-STAT5 fusion protein. GAL4-STAT5 activated replication of the plasmid containing tandem repeats of GAL4 binding sites and polyoma replication origin in BA/F3 cells. Mutation analysis of GAL4-STAT5 indicated that multiple serine residues coordinately have a role in activating replication. This is the first direct evidence indicating the potential involvement of STAT5 in replication.

当院にて90～97年に根治的放射線治療が行われたT1-2N0声門部扁平上皮癌87症例の治療成績を検討した。男女比85: 2, 年齢は38～81 (平均63) 歳, T1a 24, T1b 19, T2 44例。放射線治療は, 原則として一回2Gy, 計60～70Gyで, 少量CDDPによる化学療法がT2の7例で併用された。5年局所制御率は61%とやや不良であり, T病期別では, T1a 82%, T1b 60%と, T2 51%に比較して有意に良好であった。総線量では65Gy以上で48%, 65Gy未満が70%と線量の低い方が良好であったが, T2症例や腫瘍の反応が悪い症例に高線量が照射されていたためと思われた。他の治療因子については, 総治療期間で有意差がわずかに見られた程度で, 明らかな有意差は認められなかった。現在は, T1では66～70Gyへの線量増加, T2では70Gyの照射に化学療法の併用により, 治療成績向上を目指している。

The human UFD1L and CDC45L genes, adjacently located in the head-to-head direction on chromosome 22q11, are separated by a 884 base-pair (bp) segment constituting the putative transcriptional control region. In this region we mapped one transcription start site at 69 bp upstream of UFD1L gene, and one major and one minor start sites at 76 bp and 503 bp upstream of CDC45L gene, which are to center in the putative core promoters designated as PUFD1L, PCDC45L/major, and PCDC45L/minor, respectively. The three core promoters lacked a TATA-motif and had a high GC-content. To determine the approximate ranges for the regulatory promoters, the 884-bp fragment or those with a series of deletions were placed between firefly and renilla luciferase genes present in the head-to-head direction in a single plasmid, and the resulting plasmids were assayed for the two transiently induced enzyme activities. The PUFD1L and PCDC45L/major regulatory promoters were within 418 and 454 bp upstream of the respective start sites and their greater parts were not overlapping. The activity of PCDC45L/minor regulatory promoter was markedly enhanced when PCDC45L/major and its regulatory promoter were deleted. The deletion analyses revealed the basal activities of the three core promoters, which were enhanced by approximately twofold by the respective regulatory promoters, on the transfected DNA templates.

Expression of human papillomavirus 16 (HPV‐16) oncogenes is markedly higher in cervical cancer cells than in precancerous cells, and the elevated expression is believed to be required for the malignant phenotypes. We compared cancer cell lines CaSki (with 200 to 400 copies of HPV‐16 DNA per cell) and SiHa (with one to two copies of HPV‐16 DNA per cell) for the E7 expression in cells and the enhancer‐promoter activity of the isolated viral long control region (LCR). Although these parameters per cell were 10‐fold higher in CaSki than in SiHa, the levels of the E7 mRNA and protein per HPV DNA copy were 10‐ to 20‐fold higher in SiHa than in CaSki. Characterization of the isolated LCRs showed that, whereas the LCR from CaSki resembled the prototype in structure and activity, the LCR from SiHa, with a deletion of 38 base pairs, enhanced transcription from P97 as assayed by using a plasmid capable of expressing luciferase. The upregulation appeared to be due to removal of one of the silencer YY1‐binding sites. Furthermore, we isolated and characterized LCRs from 51 cervical cancer patients’ biopsies. Among them, one with a deletion including YY1‐binding sites and the other with a substitution in a YY1‐motif were found to enhance the transcription. These findings suggest that mutation affecting YY1‐motifs in the LCR is one of the mechanisms enhancing the viral oncogene expression in the course of progression of cancer cells.

Adeno-associated virus type 2 nonstructural protein Rep78 [621 amino acids (aa) long] affects the expression of various cellular and viral genes. In this study we examined the effects of Rep78 on expression of the luciferase gene from the human cytomegalovirus immediate-early promoter in HeLa cells and on translation of RNA encoding luciferase in rabbit reticulocyte lysate. When Rep78 and luciferase were coexpressed, the luciferase activity decreased despite increased levels of luciferase mRNA in the cells. Purified Rep78 or Rep68 fused with Escherichia coli maltose binding protein suppressed translation of luciferase RNA in vitro, but Rep52/40 fusion proteins did not. A mutated Rep78, which is 520 aa long and truncated at its C-terminus, did suppress the in vitro translation, whereas a similarly truncated Rep78 of 420 aa did not. The results indicate that Rep78/68 function to suppress gene expression through translation inhibition, which requires the N-terminal region contained within aa 1-520.

Receptors for GM-CSF, IL-3, and IL-5 are composed of two subunits: alpha, which is specific for each cytokine, and betac, which is shared by all. Although the role of betac in signal transduction has been extensively studied, the role of the alpha subunit has remained to be clarified. To analyze the role of the human (h) GM-CSF receptor alpha subunit, we constructed a chimeric receptor subunit composed of extracellular and transmembrane regions of alpha fused with the cytoplasmic region of betac, designated alpha/beta. In BA/F3 cells, chimeric receptor composed of alpha/beta,beta can transduce signals for mitogen-activated protein kinase cascade activation and proliferation in response to hGM-CSF. Although phosphorylation of Jak1 but not of Jak2 occurred with stimulation of hGM-CSF, the dominant-negative Jak2 but not the dominant-negative Jak1 suppresses c-fos promoter activation. To determine whether the chimeric receptor alpha/beta,beta is functional in vivo, we developed transgenic mice expressing the chimeric receptor alpha/beta,beta. Bone marrow cells from the transgenic mice expressing the alpha/beta,beta receptor form not only GM colonies but also various lineages of colonies in response to GM-CSF. In addition, mast cells were produced when bone marrow cells of the transgenic mouse were cultured with hGM-CSF. Thus, it appears that the cytoplasmic region of the alpha subunit is not required for hGM-CSF promoting activities, even in bone marrow cells.

Purpose: The aim of the study was to evaluate the efficacy of stereotactic radiosurgery (SRS) for thoracic tumors with megavoltage computed tomography (MVCT) from the point of view of symptom palliation as well as local control. Methods and Materials: MVCT-assisted positioning verification and real-time monitoring for a multileaf collimator (MLC) were used to enhance the accuracy of the thoracic SRS. Twenty-two thoracic tumors in 15 patients underwent the present treatment. All but 1 tumor were metastases from various primary malignancies. Eleven patients were symptomatic. The treatment site was the chest wall/pleura in 10 tumors, and the lung in 12 tumors. The median volume of the clinical target was 4.5 cc and the median peripheral dose was 20 Gy, for the lung tumors. For the chest wall/pleura tumors, the median volume of the clinical target was 40 cc and the median peripheral dose was 20 Gy. Conventional fractionated conformal radiation therapy (CRT) followed SRS in 10 tumors. Results: Of 21 tumors eligible for evaluation, there were 13 with complete responses, 6 with partial responses, and 2 without response. Duration of local control ranged from 0.6 to 82 months with a median of 8 months, with only one local recurrence seen. Immediate palliation was obtained in most symptomatic patients. Interstitial changes in the lung were limited. Autopsy performed for a patient revealed remarkable histologic effects with minimal injuries to the lung. Conclusion: The geometric accuracy of MVCT-assisted SRS appeared to enhance the clinical efficacy and safety of treatment to thoracic malignancies.

Purpose: The aim of this study is to evaluate the actual effect of irradiation for other targets in dose planning for the treatment of multiple metastases with Gamma Knife. Methods and Materials: We analyzed dose distributions for 51 targets in 10 patients with metastatic brain tumors who underwent radiosurgery with Gamma Knife for the treatment of more than one target in one session. We made dose plans with every attempt to include as many targets as possible and calculate dose distributions separately for each dose matrix. We also calculated the composite dose distribution by including the effect of all shots used. We compared these noncomposite and composite dose distributions. Results: The differences in the mean target dose between the noncomposite dose distribution and the composite one ranged from 0.0 to 4.5 Gy with a mean of 1.5 Gy and was more than 2 Gy in 12 (24%) targets. The difference tended to be larger when targets were small in volume and/or the number of targets was large. Conclusions: The effect of irradiation from the shots for other targets was not negligible in some cases. This difference of dose distribution should be considered in the analysis of clinical outcomes of cases with multiple targets treated in one session.

Flat-panel, self-scanning, solid state diagnostic x-ray imaging devices using complementary metal-oxide-semiconductor (C-MOS) arrays are under investigation. A unit device with a 5 cm by 5 cm sensor area was developed and tested. The device consists of a CsI scintillator and C-MOS detector arrays. The detector arrays are composed of a regular arrangement of pixels (256 x 256), each of which is made of a C-MOS photodiode sensor coupled to a C-MOS FET (field effect transistor). A common FET gate line is connected to all the FET gates along each column. A common date line is connected to all the FET drains of each row. The source contact of each FET is connected to that of its corresponding photodiode. A positive gate pulse applied to a gate turns on all FETs connected to the date lines. The readout continues column by column. Correlated double sampling circuits and an offset variance compensation circuit were installed to reduce noise. A sampling speed of 15 frames per second and spatial resolution of 2.5 line per mm were achieved. Noise level and maximum signal were 1.5 mV rms and 1.8 V, respectively. Image quality was considered acceptable for clinical use. It is also discussed how to fabricate a large area sensor with the unit device.