Development of a pepper-pot emittance meter for diagnostics of low-energy multiply charged heavy ion beams extracted from an ECR ion source.

Several fluorescent materials were tested for use in the imaging screen of a pepper-pot emittance meter that is suitable for investigating the beam dynamics of multiply charged heavy ions extracted from an ECR ion source. SiO2 (quartz), KBr, Eu-doped CaF2, and Tl-doped CsI crystals were first irradiated with 6.52-keV protons to determine the effects of radiation damage on their fluorescence emission properties. For such a low-energy proton beam, only the quartz was found to be a suitable fluorescent material, since the other materials suffered a decay in fluorescence intensity with irradiation time. Subsequently, quartz was irradiated with heavy (12)C(4+), (16)O(4+), and (40)Ar(11+) ions, but it was found that the fluorescence intensity decreased too rapidly to measure the emittance of these heavy-ion beams. These results suggest that a different energy loss mechanism occurs for heavier ions and for protons.

Production of beams from solid materials at Center for Nuclear Study electron cyclotron resonance ion source.

Two methods for the feed of vapor from solid materials in the Center for Nuclear Study ECR ion source are described. A rod placed near the wall of the plasma chamber, operating up to a melting point of 2600 °C, has been used for CaO, SiO2, and FeO. An oven with a number of openings, operating up to 800 °C, has been used for P2O5, Li, and S. Typical ion beam intensities of (7)Li(2+), (6)Li(3+), (40)Ca(12+), and (56)Fe(15+) are achieved 280, 75, 28, and 7 eµA, respectively. High intensity heavy ion beams are stably supplied into the azimuthally varying field cyclotron.

First results from the new RIKEN superconducting electron cyclotron resonance ion source (invited).

The next generation heavy ion accelerator facility, such as the RIKEN radio isotope (RI) beam factory, requires an intense beam of high charged heavy ions. In the past decade, performance of the electron cyclotron resonance (ECR) ion sources has been dramatically improved with increasing the magnetic field and rf frequency to enhance the density and confinement time of plasma. Furthermore, the effects of the key parameters (magnetic field configuration, gas pressure, etc.) on the ECR plasma have been revealed. Such basic studies give us how to optimize the ion source structure. Based on these studies and modern superconducting (SC) technology, we successfully constructed the new 28 GHz SC-ECRIS, which has a flexible magnetic field configuration to enlarge the ECR zone and to optimize the field gradient at ECR point. Using it, we investigated the effect of ECR zone size, magnetic field configuration, and biased disk on the beam intensity of the highly charged heavy ions with 18 GHz microwaves. In this article, we present the structure of the ion source and first experimental results with 18 GHz microwave in detail.

In situ hybridization study of the distribution of choline acetyltransferase mRNA and its splice variants in the mouse brain and spinal cord.

Choline acetyltransferase is the enzyme that catalyzes the biosynthesis of the neurotransmitter acetylcholine. Seven types of mRNA for choline acetyltransferase that differ in the 5'-noncoding region are transcribed from the cholinergic gene locus from different promoter regions and produced by alternative splicing in the mouse. Digoxigenin-labeled riboprobes and in situ hybridization histochemistry were used to investigate the expression of N1, R1, R2, R3, R4 and total choline acetyltransferase mRNA in the mouse CNS. The relative levels of choline acetyltransferase transcripts differed dramatically in distinct subdivisions of the mature cholinergic nervous system. Neurons hybridizing with antisense riboprobes for all of the five investigated splice variants (R1, R2, R3, R4 and N1) as well as those hybridizing with riboprobe for the common protein-coding region were found in a number of expected regions in the CNS. They include the basal forebrain, striatum, pontomesencephalic tegmentum, motor and autonomic nuclei of the brainstem, and spinal cord. Neurons with a moderate to very high level of expression of R1 and R2 splice variants were distributed in both the forebrain and brainstem nuclei. On the other hand, R3, R4 and N1 splice variants revealed a moderate to high level of expression in the brainstem motor and autonomic nuclei and ventral and lateral horns of the spinal cord compared to a low expression level in forebrain cholinergic structures. No expression of the N1, R1, R2, R3 and R4 splice variants was detectable in the neurons of the cerebral cortex, hippocampus and medial habenular nucleus. With the riboprobe for the common protein-coding region, the neurons of the medial habenular nucleus could be labeled at high level, while intrinsic cortical neurons were labeled at low level. Hippocampus revealed no significant hybridization for total choline acetyltransferase mRNA. These findings strongly suggested that: (1) R1 and R2 were the major splice variants expressed in the neurons of forebrain nuclei; (2) R1, R2, R3, R4 and N1 splice variants were almost equally expressed in the brainstem motor and autonomic nuclei and ventral and lateral horns of the spinal cord; (3) inferring from a paucity of other isoforms, M type choline acetyltransferase mRNA is a splice variant predominantly expressed in the cerebral cortex and medial habenular nucleus.

Production of U beam from RIKEN 18 GHz electron cyclotron resonance ion source.

For the RIKEN radio isotope factory (RIBF) project, we produced the multicharged uranium beam with two methods. To produce lower charge state U ion beams (14+-20+) we used the UF(6) gas as an ionized gas. The typical beam intensity of U(14+-20+) was 2-1 particle microA at the extraction voltage of 14 kV. To produce higher charge state U ion beam (U(35+)), we chose the sputtering method. The beam intensity was 70 particle nA at the extraction voltage of 5.4 kV. Using this method, we successfully produced multicharged U beam continuously for one month without break for RIBF commissioning.

Vesicular acetylcholine transporter-immunoreactive axon terminals enriched in the pontine nuclei of the mouse.

Information to the cerebellum enters via many afferent sources collectively known as precerebellar nuclei. We investigated the distribution of cholinergic terminal-like structures in the mouse precerebellar nuclei by immunohistochemistry for vesicular acetylcholine transporter (VAChT). VAChT is involved in acetylcholine transport into synaptic vesicles and is regarded as a reliable marker for cholinergic terminals and preterminal axons. In adult male mice, brains were perfusion-fixed. Polyclonal antibodies for VAChT, immunoglobulin G-peroxidase and diaminobenzidine were used for immunostaining. In the mouse brain, immunoreactivity was seen in almost all major cholinergic cell groups including brainstem motoneurons. In precerebellar nuclei, the signal could be detected as diffusely beaded terminal-like structures. It was seen heaviest in the pontine nuclei and moderate in the pontine reticulotegmental nucleus; however, it was seen less in the medial solitary nucleus, red nucleus, lateral reticular nucleus, inferior olivary nucleus, external cuneate nucleus and vestibular nuclear complex. In particular, VAChT-immunoreactive varicose fibers were so dense in the pontine nuclei that detailed distribution was studied using three-dimensional reconstruction of the pontine nuclei. VAChT-like immunoreactivity clustered predominantly in the medial and ventral regions suggesting a unique regional difference of the cholinergic input. Electron microscopic observation in the pontine nuclei disclosed ultrastructural features of VAChT-immunoreactive varicosities. The labeled bouton makes a symmetrical synapse with unlabeled dendrites and contains pleomorphic synaptic vesicles. To clarify the neurons of origin of VAChT-immunoreactive terminals, VAChT immunostaining combined with wheat germ agglutinin-conjugated horseradish peroxidase retrograde labeling was conducted by injecting a retrograde tracer into the right pontine nuclei. Double-labeled neurons were seen bilaterally in the laterodorsal tegmental nucleus and pedunculopontine tegmental nucleus. It is assumed that mesopontine cholinergic neurons negatively regulate neocortico-ponto-cerebellar projections at the level of pontine nuclei.

Expression of glutamine synthetase and cell proliferation in human idiopathic epiretinal membrane.

BACKGROUND/AIM: The mechanisms of the cellular origin and cell proliferation in the idiopathic epiretinal membrane (ERM) are unsolved. The aim of this study was to examine the expression of cell cycle related molecules and glutamine synthetase (GS), which is expressed in Müller cells and their processes, in ERM tissues. METHODS: The ERMs were surgically removed using pars plana vitrectomy. Formalin fixed, paraffin embedded ERM tissues were analysed by immunohistochemistry with anti-cyclin D1, p27 (KIP1), proliferating cell nuclear antigen (PCNA), and GS antibodies. RESULTS: The histopathological findings showed that all the ERMs consisted of oval or spindle mononuclear cells with thin collagen-like tissues. Immunoreactivity for GS was detected in collagen-like tissues of ERM, presenting a continuous, isodense pattern. GS immunopositive cells in all cases expressed PCNA in their nuclei. Nuclear immunoreactivity for cyclin D1 was noted in the ERM constituent cells, whereas p27 (KIP1) positive nuclei were not detected. CONCLUSION: Cyclin D1 and PCNA were expressed in the idiopathic ERM, which was mainly derived from Müller cells and extensions of their processes.

Vertical-torsional oscillations and dissociated bilateral horizontal gaze palsy in a patient with a pontine cavernous angioma.

We report the case of a 16 year old girl with vertical-torsional oscillations. She had a 4 year history of bilateral horizontal gaze palsy caused by a cavernous angioma in the medial part of the dorsal pons. She presented with vertical oscillopsia that had worsened during the past 3 months. Unilateral three dimensional eye movements and bilateral horizontal eye movements were recorded using a magnetic search coil method and direct current electro-oculography, respectively. She had vertical-torsional oscillations (average frequency: 3.0 Hz) leaving vertical saccades and pursuits intact. The average amplitudes of the vertical and torsional components were 2.0 degrees and 0.6 degrees , respectively. Her horizontal rapid eye movements were severely impaired; however, her horizontal pursuits and slow phases of vestibulo-ocular reflex were only partially impaired (gain<0.3, oculomotor range<+/-9 degrees ). Convergence and divergence were intact. Lesions involving the medial part of the dorsal pons and bilateral paramedian pontine reticular formation can induce vertical and torsional oscillations without disruption of vertical rapid eye movements.

[Emergency pleuropneumonectomy via anterior approach to treat chronic hemorrhagic empyema due to massive hemoptysis].

A 67-year-old man with a history of surgical resection of the superior lobe of the left lung and thoracoplasty due to pulmonary tuberculosis occurring approximately 40 years previously, was admitted to the hospital due to recurrent hemoptysis. X-ray films and computed tomography (CT) scans of the chest showed the left thoracic cavity to be filled with empyema, compressing the inferior lobe downward. Since three unsuccessful attempts were made at bronchial artery embolization for hemostasis, yielding hemoptysis of approximately 1,000 ml, emergency surgery was performed. To prevent massive intra-operative hemoptysis, the left pulmonary artery was blocked by median sternotomy. A transverse incision was then made, and thus pleuropneumonectomy could be safely performed. Since it allows early blocking of blood vessels surrounding the hilum of the lung and the main bronchus, anterior approach is useful in treating hemorrhagic empyema and wet pleurisy with internal fistula.

Characterization of minute differences between genomes of strains of Penicillium nalgiovense using subtractive suppression hybridization without cloning.

AIMS: Characterization of integrated DNA fragments of unknown base sequences from foreign species using the genetically modified mould Penicillium nalgiovense. METHODS AND RESULTS: A modified suppression subtractive hybridization method was deployed in order to detect and characterize foreign genes. Combined with a special two-dimensional polyacrylamide gel electrophoretic technique the usual background was eliminated from the prospective foreign polymerase chain reaction fragments according to their base composition (Müller et al. 1981). CONCLUSIONS AND SIGNIFICANCE AND IMPACT OF THE STUDY: DNA fragments obtained from the procedure were suitable for direct DNA sequencing. Each DNA fragment derived from the tester genomic DNA was found to be completely absent in the driver organism.

Brainstem auditory regions in mice: expression of nociceptin/orphanin FQ precursor mRNA in select neurons.

Nociceptin peptide-receptor system is known to be essential for the regulation of hearing ability. The mRNA for nociceptin precursor protein is highly expressed in the brainstem. We explored a detailed hybridohistochemical expression pattern of the nociceptin precursor mRNA in the mouse brainstem, and identified positive cells in several auditory brainstem nuclei. Positive cells were seen in the dorsal and ventral nuclei of the lateral lemniscus, the rostral periolivary region, the lateroventral and medioventral periolivary nuclei, the dorsal periolivary region, the superior paraolivary nucleus, and the external cortex and dorsal cortex of the inferior colliculus. Of these, the medioventral and lateroventral periolivary nuclei, the major sites of origin of olivocochlear bundle, were most populated by positive cells.

Prognosis of resected non-small cell lung cancer patients with carcinomatous pleuritis of minimal disease.

OBJECTIVE: The purpose of this study was to clarify the prognosis of resected non-small cell lung cancer (NSCLC) patients with carcinomatous pleuritis of minimal disease which might be considered as the next advanced stage of positive pleural lavage cytology. METHOD: The data were collected from a questionnaire survey on the survival of the patients with carcinomatous pleuritis found at thoracotomy from 1985 to December 1994 which was conducted by the Japan Clinical Oncology Group (JCOG). RESULTS: Out of 227 patients with carcinomatous pleuritis found at thoracotomy who had available information on a survival, 100 patients who underwent a resection of the primary tumor had carcinomatous pleuritis of minimal disease defined based on the criteria of the Japan Lung Cancer Society. The mean malignant fluid volume (+/-S.E.) was 37.1 (6.3) ml and the mean number of pleural disseminated nodules was 5.6 (0.9). A lobectomy was performed in 79 patients, a pneumonectomy in 11 and a limited resection in ten. The 3- and 5-year survival rates were 31.8 and 22.8%, respectively. CONCLUSIONS: The prognosis of resected NSCLC patients with carcinomatous pleuritis of minimal disease was unexpectedly good. This indicates that no fine line may exist between positive pleural lavage cytology findings and the aforementioned lesion.

Prognosis of non-small cell lung cancer patients with positive pleural lavage cytology after a thoracotomy: results of the survey conducted by the Japan Clinical Oncology Group.

OBJECTIVE: The purpose of this study was to clarify the prognosis of non-small cell lung cancer patients without pleural effusion whose intrapleural cancer cells were detected by a cytologic examination of pleural lavage fluid obtained immediately after a thoracotomy. METHOD: A questionnaire survey on the survival of the patients with positive pleural lavage cytology from January 1985 to December 1994 was performed by the Japan Clinical Oncology Group. RESULTS: According to the data collected from 15 institutions, 1890 non-small cell lung cancer patients without pleural effusion underwent pleural lavage cytology immediately after thoracotomy and 142 (7.8%) of them were found to have intrapleural cancer cells detected by the cytological analysis. The information of survival on 113 patients was available. This comprised of 64 males and 49 females with a mean age of 64.6 years. The predominant histologic type was adenocarcinoma (74%). Out of these 113 patients, 109 (97%) underwent a surgical resection. The 5-year survival rate was 30% in all patients, 49% in pathological stage I (n=35), 23% in stage II (n=20) and 26% in stage IIIA (n=34). CONCLUSION: Patients with a positive pleural lavage cytology in pathological stage I or II appear to have a poor 5-year survival rate.

[Tension pneumothorax after simultaneous bilateral lung resection].

A 72-year-old man was admitted to our hospital because of an abnormal shadow on chest X-ray film. Chest CT showed a mass 6 cm in diameter in left S1 + 2, and a small round mass in right S2. Left side mass was diagnosed squamous cell carcinoma by transbronchial biopsy, but right side mass was unidentified. We performed partial resection for a right S2 mass with VATS, and then left upper lobe lobectomy and mediastinal lymph node dissection simultaneously. Pathological examination revealed the right mass was hamartoma. He discharged on 16 postoperative days uneventfully. But 3 days after he was sent to our hospital on emergency because dyspnea and unconscious. Chest X-ray revealed right side tension pneumothorax, then he was recovered by chest tube insertion. At re-thoracotomy we confirmed air leakage was occurred from a ruptured bulla that was leaved at first operation.

[A case of pulmonary cavernous hemangioma: immunohistological examination revealed its endothelial cell origin].

A 29-year-old woman was referred to our hospital for an abnormal shadow on chest roentgenogram. She had no symptom but its shadow was pointed out about 20 years ago. Chest CT scan showed a sharply demarcated homogenous mass measured 10 x 10 mm in the S4 segment. The tumor was resected with video-assisted thoracoscopic surgery under CT-guided marking wire inserted. Microscopic examination suspected cavernous hemangioma. Immunohistological staining demonstrated most lining cells of the cavernous structure stained positively for von Willebrand factor antibody, which suggests that this tumor was associated with endothelium. Then we decided that this tumor was pulmonary cavernous hemangioma.

Oculopharyngeal muscular dystrophy in a Japanese family with a short GCG expansion (GCG)(11) in PABP2 gene.

Clinicopathological and molecular genetic findings on a new Japanese family with oculopharyngeal muscular dystrophy are reported. The family has 54 members, ten of whom are affected (seven male and three female), in 3 generations. Three affected males, one affected female and one unaffected female of seven living siblings in the third generation were examined. Bilateral ptosis developed in the 4th and 5th decades in the three male cases, and in the 7th decade in the female, and this was followed by diplopia, nasal voice, dysphagia and muscle weakness. In addition, severe external ophthalmoplegia, dysphonia, and proximal amyotrophy were prominent in this family. Electromyographs revealed myogenic/neurogenic changes, and computed tomography disclosed selective muscle wasting with fatty replacement, predominantly in the lower extremities. Muscle biopsy in the four affected patients showed variation in fiber size, and the presence of small angulated fibers and occasional rimmed vacuoles. Electron microscopic examination revealed an accumulation of filamentous inclusions in muscle fiber nuclei. DNA analysis identified that (GCG)(6) in the PABP2 gene was expanded to (GCG)(11) in the four affected cases examined. All studies were negative in the one unaffected. These results confirm that OPMD is caused by GCG short expansion and provides insights into the genetic mechanisms which may contribute to adult onset myopathy, confined to oculopharyngeal muscles.

[Mediastinal mature teratoma perforated into the pericardial sac: a case report].

Mature teratomas occasionally rupture into adjacent organs such as lung, bronchus, mediastinum and pericardial sac. However, perforation into the pericardial sac is rare. We experienced a case of mediastinal mature teratoma perforated into the pericardial sac. A 16-year-old man was admitted to our hospital due to sudden severe anterior chest pain. Chest X-ray showed a mass shadow in the right middle lung field. Chest CT scan and MRI demonstrated a heterogeneous mass with fat component in the right anterior mediastium adjacent to the pericardium. Some squamous cells were obtained from the mass by CT guided percutaneous needle biopsy. Operation was performed with the diagnosis of mediastinal teratoma. The mass adhered to the pericardium and turbid pericardial effusion was noted. The mass was removed with the pericardium. The mass was 9 x 6.5 x 6 cm in size, which contained yellow sebaceous material and a tuft of white hair. The pathological diagnosis of the mass was mature cystic teratoma with perforation into the pericardial sac.

The prognosis of patients with non-small cell lung cancer found to have carcinomatous pleuritis at thoracotomy.

Non-small cell lung cancer with carcinomatous pleuritis is considered to be a contraindication of surgical resection. The objective of this study was to clarify the prognosis of patients with non-small cell lung cancer in whom carcinomatous pleuritis was found at thoracotomy. A questionnaire survey on the survival of patients with carcinomatous pleuritis found at thoracotomy between January 1985 and December 1994 was conducted by the Japan Clinical Oncology Group. According to the data collected from 21 hospitals, 8813 patients with non-small cell lung cancer underwent thoracotomy, 284 (3.2%) of whom were found to have carcinomatous pleuritis. Information on survival was available for 227 of these patients, 34 (15%) of whom underwent thoracotomy alone without resection, whereas 193 (85%) underwent surgical resection. Of the 193 resected patients, 155 had no macroscopical residual tumor apart from the carcinomatous pleuritis. The 5-year survival rate was 14%. According to a univariate analysis, female sex, the presence of adenocarcinoma, a tumor size of less than 3.0 cm, no clinical lymph node metastasis, and no macroscopical residual tumor had a significantly favorable impact on survival. A multivariate analysis revealed that the extent of clinical lymph node metastasis (P = 0.006), histology (P = 0.028), and the absence or presence of a macroscopic residual tumor after the operation (P = 0.045) were predominant prognostic factors. The 5-year survival rate of 83 patients with three positive variables was 24%. The prognosis of patients with adenocarcinoma found to have carcinomatous pleuritis at thoracotomy was not necessarily unfavorable if there was no clinically detected lymph node metastasis and no residual tumor apart from the carcinomatous pleuritis.

Comparative distribution of GABAergic and peptide-containing neurons in the lateral lemniscal nuclei of the rat.

By immunostaining, neurons expressing peptides (dynorphin and corticotropin-releasing factor, CRF) and glutamate decarboxylase (GAD), a GABA-synthesizing enzyme, were precisely mapped in the rat lateral lemniscal nuclei. While GAD neurons were numerous and preferably localized in the dorsal (DLL) and ventral (VLL) nuclei, neurons expressing these peptides were less numerous and localized primarily in the intermediate (ILL) nucleus of the lateral lemniscus. The ILL nucleus was shown to project to the inferior colliculus and to express Fos rapidly in response to peripheral acoustic stimulation, suggesting that the ILL nucleus may take part in non-GABAergic relay of acoustic information in the lateral lemniscus.

[Regrowth of bullae around the staple-line is one of the causes of postoperative recurrence in thoracoscopic surgery for spontaneous pneumothorax].

Since August 1994, we have performed 65 thoracoscopic surgeries for spontaneous pneumothorax. Our operative method is partial resection of the lung with bullae using endoscopic autosuture. Three patients underwent reoperation because of persistent air leakage in one case and postoperative recurrences in two cases. In addition, we performed a second operation in one case that had undergone thoracoscopic surgery for spontaneous pneumothorax in another hospital. At the second operation, regrowth of bullae was found at the edge of staple-line in three of the 4 cases, and in one of these cases, such regrown bullae seemed to be a cause of recurrence of pneumothorax. The regrowth of the bullae was caused by incomplete resection at the initial surgery in one case. Such incomplete resection and oversight were not noticed in the review of the videotape of the initial surgeries in two cases. Reinforcement of the staple-line is necessary for prevention of recurrence of pneumothorax.