Copper-catalyzed cyclization of N-allylhalodifluoroacetamides: an efficient synthesis of alpha,alpha-difluorinated gamma-lactams.
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Biomedical subjects
Publications and source records attributed to H Nagashima.
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We report the case of a 42-year-old woman with Klippel-Feil syndrome, who showed severe hypermobility of the upper cervical spine without neurological involvement for more than 40 years. Radiographs revealed the presence of the odontoid bone and fusion of the atlas, odontoid bone, and occiput. Congenital fusion was present from the axis to C5 as a block vertebra. Lateral flexion-extension radiographs revealed severe hypermobility at the junction between the odontoid bone and the axis. Prophylactic surgical stabilization has been recommended in patients with severe hypermobility, but adjacent disc problems may possibly occur at the unfused levels in the future. We believe that early prophylactic stabilization should not be indicated for Klippel-Feil syndrome without neurological involvement only because of hypermobility.
We developed a new method to measure the nerve conduction velocity of a single digital nerve. In 27 volunteers (27 hands), we separately stimulated each digital nerve on the radial and ulnar sides of the middle and ring fingers. A double-peaked potential was recorded above the median nerve at the wrist joint when either the radial-side nerve or the ulnar-side nerve of the middle finger was stimulated. The first peak of this potential had disappeared after the digital nerve was blocked under the stimulating electrodes, and the peak appeared again coinciding with the decrease of anesthesia. Shifting the stimulating electrodes on the digital nerve resulted in no significant difference in the peak conduction velocity. It is possible that each peak of the potential was attributable to conduction of an action potential along one of the two digital nerves. This new method allows the assessment of a single digital nerve, and may be clinically useful for assessing the rupture of a digital nerve and the sensory nerve action potentials in carpal tunnel syndrome.
Endogenous ethanol was observed by nuclear magnetic resonance spectroscopy in the course of screening for cerebrospinal fluid of the patients with cervical myelopathy. Ethanol was detected in 10 out of 20 patients. It seems likely that the presence of endogenous ethanol is related to the severity of myelopathy. Also, the concentration of ethanol was correlated with that of lactate in the cerebrospinal fluid. This implies that ethanol may be formed as the end product of glycolysis or in an unknown pathway in the case of severely insulted myelonic tissues.
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The sleep patterns were examined during the simulated 30-m nitrox saturation dives. The standard polysomnography of 15 divers was recorded for a total of 255 nights, as were patterns of change or consistency in sleep variables. A reduction of total sleep time in accordance with the lengthening of sleep latency and the wake after sleep onset was observed through the latter part of the bottom period to the post-dive period, but the other sleep variables did not show any changes. These findings suggest that decompression and the psychological stress due to being in the closed environment of a hyperbaric chamber for a long time have effects on divers' sleep.
We analysed the effects of age and gender on the habitual sleep-wake rhythm in 2252 randomly selected subjects living in Shimonoseki, Japan. Subjects were divided into 21 age groups with a matching number of males and females for each. During the period from primary school to adolescence, the bedtime became delayed and sleep length decreased with age. After that period, with increasing age, bedtime became earlier and sleep length increased. The number of awakenings and the length of daytime naps increased markedly with epoch after 50 years and 70 years of age, respectively. Gender differences were considered to be due to the women's social and domestic customs in Japan.
Intracranial aneurysm is a rare cause of hemifacial spasm and most of the previously reported cases are treated with surgical microvascular decompression. Authors report a case of hemifacial spasm caused by a dissecting aneurysm located at the vertebrobasilar junction which improved after endovascular obliteration of the affected vertebral artery with coils. The patient was a 69-year-old man with 20 months' history of left hemifacial spasm. A vertebral angiogram showed an irregular dilatation of the right vertebral artery associated with aneurysmal dilatation at the vertebrobasilar junction. Endovascular obliteration of the abnormally dilated right vertebral artery proximal to the vertebrobasilar junction was performed. The hemifacial spasm gradually improved after the embolisation and disappeared 6 months later. Endovascular proximal obliteration of the vertebral artery may have changed the hemodynamic force inside the aneurysm and eliminated the vascular compression at the root exit zone of the facial nerve.
The aneurysm located in the internal carotid juxta-dural ring region is difficult to surgically obliterate. At surgery, careful drilling of the anterior clinoid process is mandatory, especially when a laterally projecting aneurysm protrudes to or inside the anterior clinoid process.In this paper, treatment procedures using the skull base techniques with intravascular coil embolisation are described by showing a case.
The MAGE-B (MAGE-B1, -B2, -B3, and -B4) genes share strong homology with the MAGE-A gene family. MAGE-B1 and -B2 encode common tumor-specific peptide antigens. There is, however, still very little information about the expression of these genes in human gastro-intestinal carcinomas. We investigated the expression of MAGE-B1 and -B2 genes in 29 cell lines and 53 clinical tumor samples of esophageal squamous cell carcinoma by reverse transcription polymerase chain reaction (RT-PCR). MAGE-B1 and -B2 gene transcripts were detected by RT-PCR in 1 (3%) and 6 (21%) cell lines, and in 9 (17%) and 17 (32%) clinical samples, respectively. Among them, 7 / 29 (24%) cell lines and 19 / 53 (36%) clinical samples expressed at least either MAGE-B1 or -B2. A significant correlation was found between negative MAGE-B gene expression and vascular invasion (P = 0.008). In 45 out of 53 esophageal carcinoma RNA samples, the MAGE-A1, -A2, and -A3 genes were detected in 27 (60%), 23 (51%), and 30 (67%) samples, respectively, while the MAGE-B genes were detected in 18 (40%) samples. The frequency of MAGE-B gene expression in esophageal carcinoma was relatively higher than that observed for gastric or colorectal carcinomas (12% and 2%, respectively). Therefore, the MAGE-B genes could be used as targets in specific immunotherapy of esophageal squamous cell carcinomas.
OBJECTIVES: Salivary gland organogenesis was evaluated in NOD mice, an animal model for autoimmune exocrinopathy, to determine when disease onset is first present in the target tissues. METHODS: Submandibular glands were removed for histological, immunohistochemical and biochemical evaluation from neonatal NOD and congenic strains as well as healthy control C57BL/6 mice. RESULTS: Histomorphological analyses of neonatal submandibular glands, the primary target for autoimmune exocrinopathy at 1 day postpartum, revealed delayed morphological differentiation during organogenesis in autoimmune-susceptible NOD mice when compared to nonsusceptible C57BL/6 mice. Acinar cell proliferation was reduced, while expression of Fas, FasL and bcl-2 were increased. Acinar cell proliferation was reduced, while expression, of Fas, FasL and bcl-2 were increased. Throughout the preweaning period (21 days) submandibular glands from NOD and NOD congenic strains aberrantly expressed an increased matrix metalloproteinase (MMP)-2 and MMP-9 activity. Substitution of two susceptibility alleles (Idd3 and Idd5) in NOD mice resulted in an hierarchical and additive reversal of delayed organogenesis, elevated MMP-9 activity, and aberrant expression of parotid secretory protein. DISCUSSION: NOD-derived mice whose submandibular glands showed normal organogenesis did not progress to develop autoimmune exocrinopathy. Altered organogenesis of target tissue may therefore provide a cellular microenvironment capable of activating autoimmunity.
Using the NOD mouse, a model for type 1 diabetes, we examined how reduced concentrations of epidermal growth factor (EGF) in the saliva, after onset of type 1 diabetes, affect oral wound healing. Diabetic NOD/LtJ mice on insulin therapy, prediabetic NOD/LtJ, and age- and sex-matched BALB/cJ mice were given a cutaneous tongue punch and allowed to undergo normal healing. With diabetes onset and a reduction in saliva-derived growth factor levels, the rate of tongue wound healing was reduced compared with nondiabetic NOD/LtJ and healthy BALB/cJ mice. Addition of exogenous EGF to the drinking water did not accelerate the rate of healing in BALB/cJ or prediabetic NOD/LtJ; however, diabetic NOD/LtJ mice exhibited accelerated wound healing similar to healthy mice. These results demonstrate that loss of growth factors from saliva is associated with profoundly reduced oral wound healing, suggesting that therapeutic treatment with topical delivery may be beneficial to patients with type 1 diabetes and oral wound complications.
Tumors may escape a host's immune response by means of various mechanisms. The Fas (CD95/APO-1)/Fas ligand (FasL) system is one of the major apoptotic pathways. Recently, it has been reported that tumor cells can express FasL, induce apoptosis in tumor infiltrating lymphocytes, and thus can escape host immune surveillance. In gastric carcinoma, tumor progression by way of the lymphatics is often seen, and lymph node metastasis is a critical factor influencing the recurrence of cancer and its prognosis. We, therefore, investigated the relationship between the expression of FasL and the lymphatic spread of gastric carcinoma. FasL-expression was examined by an immunohistochemical method using 100 surgically resected gastric carcinomas and 55 metastatic lymph nodes. Apoptotic cells among tumor infiltrating T lymphocytes were detected by T lymphocyte staining and the terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL) method in a series of sections of metastatic lymph nodes. FasL-expression was detected in 86% of primary lesions and 71% of metastatic lymph nodes. In cases with high levels of FasL-expression, the observed expression of lymph node metastases was significant (p=0.047). Moreover, FasL-positive cases with both primary lesions and metastatic lymph nodes showed also distant lymph node metastasis beyond the regional lymph nodes (p=0.030). Apoptosis among tumor infiltrating T lymphocytes was more frequently seen in FasL-positive lesions (p=0.057). Furthermore, patients with FasL-negative primary lesions tended to exhibit longer survival times than patients with FasL-positive primary lesions. The results suggest tumor escape through the lymphatic pathway via FasL-expression in gastric carcinomas.
BACKGROUND AND PURPOSE: Diagnostic selective cerebral angiography is commonly performed via transfemoral and transbrachial approaches. With these approaches, however, patients occasionally suffer serious complications. The purpose of this study was to evaluate the feasibility, efficacy, and safety of a transradial approach as an alternative to the transfemoral and transbrachial approaches. METHODS: Between October 1998 and September 1999, transradial cerebral angiography was performed in 166 consecutive patients in a single center as a diagnostic procedure. Before the procedure, we confirmed the collateral blood supply to the hand from the ulnar artery using a modified Allen test. Regular catheterization techniques were practiced using our newly designed 120-cm-long 4F catheter. In 42 patients, anticoagulant and/or antiplatelet therapy was given perioperatively. RESULTS: Twelve of the 166 patients proved to be poor candidates for the transradial approach, owing to restlessness (n = 9), lack of collateral blood supply via the ulnar artery (n = 2), and brachial artery stenosis (n = 1). The radial artery was successfully punctured and cannulated in the remaining 154 patients. Selective catheterization of the intended vessels was obtained in all carotid and vertebral angiographic procedures with no major vascular complications. CONCLUSION: Compared with transfemoral and transbrachial approaches, the transradial approach is a less invasive and safer technique for selective cerebral angiography and may warrant consideration as a standard procedure. Anticoagulant or antiplatelet therapy need not be discontinued for this method.
The MAGE gene is selectively expressed in cancer tissues such as melanoma or gastrointestinal carcinomas, whereas no expression is observed in normal tissues except testis. There are several reports of successful induction of HLA class I-restricted antitumor CTLs using MAGE peptides, and some clinical trials with these immunogenic peptides were reported as effective for some patients with malignant melanoma. However, there are no similar studies in gastrointestinal carcinomas, which are important neoplasms. Autologous dendritic cells (DCs) were generated ex vivo and were pulsed with MAGE-3 peptide, depending on the patient's HLA haplotype (HLA-A2 or A24). Patients were immunized with DC pulsed with MAGE-3 peptide every 3 weeks at four times. Twelve patients with advanced gastrointestinal carcinoma (six stomach, three esophagus, and three colon) were treated, and no toxic side effects were observed. Peptide-specific CTL responses after vaccination were observed in four of eight patients. Improvement in performance status was recognized in four patients. Tumor markers decreased in seven patients. In addition, minor tumor regressions evidenced by imaging studies were seen in three patients. These results suggested that DC vaccination with MAGE-3 peptide is a safe and promising approach in the treatment of gastrointestinal carcinomas.
A 28-year-old man was admitted because of dyspnea on effort. His tricuspid valve had been affected by granulocytic sarcoma and manifested tricuspid valve stenosis 8 years previously. After chemotherapy and radiation therapy, the tumor had disappeared and the tricuspid valve stenosis was relieved. Echocardiography showed that the posterior leaflet of the mitral valve was affected by the tumor, and Doppler ultrasonography revealed mild mitral valve stenosis. Biopsy of the anterior chest wall detected granulocytic sarcoma. Chemotherapy was started. The tumor size was reduced and the mitral valve stenosis became slight. Primary cardiac granulocytic sarcoma is very rare and stenosis of the atrioventricular valve by relapse of this tumor after complete remission is extremely unusual.
The effects of calcium channel blockers (CCBs) verapamil and diltiazem on the toxicity of rubratoxin B in HL60 cells were investigated. Treatment of rubratoxin B caused a considerable rate of blebbing, fragmentation and condensation of cells. The rate of this morphological change was much lower in the concomitant rubratoxin B and CCBs-treated cells than in the cells treated only with rubratoxin B. Cell viability was determined by measuring mitochondrial succinic dehydrogenase activity and the rate of cell proliferation. The results of these assays were of the same tendency as that of the morphological study. CCBs attenuated rubratoxin B's toxicity on cell viability because of their protective action. Rubratoxin B induced apoptosis in the presence of internucleosomal fragmentation. In contrast, concomitant rubratoxin B and CCBs treatment did not. Taken together, the above results indicated that CCBs impaired the toxicity including morphological change, cell viability and apoptosis caused by rubratoxin B.