Biomedical subjects
Publications and source records attributed to M Asai.
[figure: see text] Mesityllithium was found to be an excellent selective lithiating agent to prepare aryllithium compounds having alkoxycarbonyl groups. To extend our studies on chemoselective lithiation, an important precursor for the synthesis of camptothecin was prepared using a halogen-lithium exchange reaction followed by an intramolecular 1,2-addition.
BACKGROUND: Previous studies have shown that nitric oxide (NO) synthase inhibitors show preclinical antidepressant-like properties, suggesting that NO is involved in the pathogenesis of depression. The purpose of this study is to examine whether or not NO production increases in depressed patients. METHODS: Plasma nitrate concentrations, an index of NO production, were measured by high-performance liquid chromatography in depressed patients (n=17) and compared with patients suffering anxiety (n=6) and with healthy controls (n=12). RESULTS: Plasma nitrate concentrations were significantly higher in depressed patients than in patients with an anxiety disorder (P<0.05) or in controls (P<0.01). LIMITATIONS: The study group was small. The source of the surplus production of NO in patients with major depressive episode remains unclear. CONCLUSIONS: These results suggest that NO production is increased in depression.
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Polyamines are a ubiquitous group of amines that play diverse biological roles. In the anterior pituitary, intracellular polyamine levels are reported to show diurnal changes, although the biological significance remains to be elucidated. In this study, we examined the effects of polyamines on the transcriptional activity of the rat pro-opiomelanocortin (POMC) gene using AtT20PL, a clone of the AtT20 cell line in which an approximately 0.7 kb of the rat POMC 5' promoter-luciferase fusion gene was stably incorporated. The results showed that three representative polyamines (putrescine, spermidine and spermine) all stimulated POMC promoter activity in a time- and dose-related manner, spermine showing the most potent effect (maximum approximate three-fold increase). This effect was not observed under treatment with actinomycin D, suggesting the effect of polyamine at the transcriptional level. On the other hand, methylglyoxal bis (guanylhydrazone), an inhibitor of polyamine synthesis, showed the opposite effect, further supporting the positive role of intracellular polyamines. Taken together, our findings suggest that polyamines are involved in the regulation of POMC gene expression (especially in terms of diurnal changes) in corticotroph cells. The precise molecular mechanisms of polyamine effects await further research.
BACKGROUND: In patients with paroxysmal atrial fibrillation (Paf), the identification of the coexistence of sinus node dysfunction (SND) has therapeutic implications. This study sought to prospectively determine whether SND in patients with Paf would be identified by use of atrial early potential (EP), low-amplitude potentials early in signal-averaged P wave. METHODS: The study population consisted of 149 patients with Paf. Signal-averaged electrocardiography was recorded with the P-wave-triggering technique. The root mean square voltage for the initial 30 MS and the duration of initial low-amplitude signals < 4 microV of signal-averaged P wave were measured in the vector magnitude. The criteria of EP were defined as "the root mean square voltage for the initial 30 MS < 3.0 microV and the duration of initial low-amplitude signals < 4 microV >22 MS." SND was diagnosed by use of the conventional 12-lead electrocardiography, 24-hour Holter monitoring, and bedside electrocardiographic monitoring. RESULTS: Thirty-eight of 149 patients with Paf had EP. Eighteen (47%) of 38 patients with Paf and EP had SND, whereas SND was found in only 5 (5%) of the other 111 patients with Paf without EP (P <.0001). EP gave a sensitivity of 78% and a specificity of 84% for the detection of SND in patients with Paf. CONCLUSION: EP would be useful for the identification of SND in patients with Paf.
Pyoderma gangrenosum is a neutrophilic dermatosis that may be associated with myeloid malignancies. Less information is available about the association of pyoderma gangrenosum with lymphoid malignancies. We present, to our knowledge, the first case of pyoderma gangrenosum associated with biphenotypic acute leukemia wherein the malignant cells show a phenotype specific for myelogenic and lymphocytic leukemia. Histopathologic examination revealed rather nonspecific features without involvement of leukemic cells in the skin lesions. Treatment with systemic steroids was followed by characteristically rapid healing of the skin lesion.
In order to study the characteristics of pediatric patients (< or = 15 years at onset) with endolymphatic hydrops disorders, we selected 5 patients with Ménière's disease (MD) and 3 patients with delayed endolymphatic hydrops (DEH) from 7418 patients who had visited the Neurotological Clinic of the Toyama Medical and Pharmaceutical University Hospital between 1979 and 1999. Clinical features were characterized as follows: (i) pediatric MD patients were rare, comprising approximately 1.5% of all the 337 MD patients in the sample; (ii) a fluctuating hearing loss, strong positive response in glycerol test, high SP/AP amplitude ratio in electrocochleography and moderate positive response in furosemide vestibulo-ocular reflex test were recorded; (iii) in 2 of the 5 pediatric MD patients, vertiginous attacks had persisted for a long period and they had undergone surgical procedures (sac operation and vestibular neurectomy); and (iv) the ipsilateral type of DEH was observed in 2/3 children, and contralateral DEH in 1/3.
OBJECTIVE: To determine whether cardiac iodine-123 metaiodobenzylguanidine ((123)I MIBG) imaging is useful in predicting the prognosis of patients with chronic heart failure. DESIGN: Cardiac (123)I MIBG imaging was done on entry to the study. The cardiac MIBG washout rate was calculated from anterior chest view images obtained 20 and 200 minutes after injection of the isotope. Study patients were divided into two groups with washout rates above and below 27% (the mean value + 2 SD obtained in 20 normal subjects), and were then followed up. SETTING: Tertiary referral centre. PATIENTS: 79 patients with chronic heart failure in whom the left ventricular ejection fraction was less than 40%. RESULTS: There were 37 patients in group 1 (washout rate of >/= 27%) and 42 in group 2 (< 27%). During a follow up period of between 1 and 52 months, eight patients died suddenly and five died of worsening heart failure in group 1, while none died in group 2; 13 patients in group 1 and four in group 2 were admitted to hospital for progressive heart failure. Kaplan-Meier analysis showed that group 1 had a significantly higher mortality and morbidity (p = 0.001 and p < 0.001, respectively) than group 2. CONCLUSIONS: Cardiac (123)I MIBG washout rate seems to be a good predictor of prognosis in patients with chronic heart failure.
The V(1b) vasopressin receptor, expressed mainly in the corticotroph of the anterior pituitary, mediates the stimulatory effect of vasopressin on ACTH release. To clarify the regulation of receptor expression, we cloned, sequenced (up to approximately 5 kb from the translation start site), and characterized the 5'-flanking region of the rat V(1b) receptor gene. We identified the transcription start site by amplification of cDNA ends and found a new intron within the 5'-untranslated region (5'-UTR) by comparing the sequence with that of cDNA. We then confirmed that the obtained promoter indeed has transcriptional activity by use of the luciferase reporter in AtT-20 mouse corticotroph cells. Interestingly, there were five short upstream open reading frames (uORFs) located within the 5'-UTR that were found to suppress V(1b) expression. Subsequent mutational analyses showed that the two downstream uORFs have an inhibitory effect on expression in both homologous and heterologous contexts. Furthermore, the inhibition did not accompany a parallel decrease in mRNA, suggesting that the suppressive effect occurs at a level downstream of transcription. Taken together, our data strongly suggest that the expression of the V(1b) receptor is regulated at the posttranscriptional as well as transcriptional level through uORFs within the 5'-UTR region of the mRNA. Whether the uORF-mediated regulation of V(1b) expression is functionally linked to any intracellular and/or extracellular factor(s) awaits further research.
Although opioid peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis, their role in pro-opiomelanocortin (POMC) gene expression at the pituitary level is not known. We therefore examined the effects of opioid receptor agonists, including recently discovered endogenous opioid peptides, on POMC gene expression using the AtT20PL cell line, a subclone of AtT20 in which the rat POMC 5'-promoter-luciferase fusion gene was stably incorporated. The endogenous mu-opioid receptor agonists endomorphin 1 and 2 had no effect on either basal or corticotropin-stimulating-hormone-induced POMC expression. This was also the case with the delta-agonist BUBUC, the kappa-agonist U50488H and the orphan receptor agonist orphanin FQ. In contrast, the synthetic mu-agonist loperamide significantly inhibited basal and yet enhanced cAMP-induced POMC expression. The inhibitory effect of loperamide was mimicked by the calmodulin antagonist W7 and antagonized by the calcium channel blocker nifedipine, whereas neither the inhibitory nor the enhancing effect of loperamide was influenced by the opioid antagonist naloxone. These results suggest that the synthetic mu-agonist loperamide has a modulatory effect on the 5'-promoter activity of the POMC gene. This effect does not seem to be mediated through the classical mu-opioid receptor but rather in part through a calcium/calmodulin-related mechanism.
Although GHRH is known to play a pivotal role in the regulation of the GHRH-GH-IGF-I axis, the molecular mechanism of GHRH gene expression has not yet been examined. Here we studied the transcriptional regulation of the GHRH gene 5'promoter using an in vitro experimental model system. We especially focused on the role of homeobox transcriptional factor Gsh-1, because a dwarf phenotype and abolished GHRH expression was observed in Gsh-1 knockout mice. First, we cloned human Gsh-1, which showed 87.3% homology with mouse Gsh-1 at the nucleotide level. When the 5'-promoter region of the rat GHRH gene was introduced into the human placental cell line JEG-3, in which we found the endogenous expression of Gsh-1 as well as GHRH mRNA, substantial transcriptional activity of the promoter was recognized. Promoter activity was further enhanced by overexpression of Gsh-1 protein, whereas it was substantially reduced by elimination of Gsh-1 binding sites. EMSA confirmed the actual binding of Gsh-1 on the multiple binding sites of GHRH gene promoter. Finally, coexpression of CREB-binding protein significantly enhanced the Gsh-1-induced GHRH gene expression, suggesting the cooperative role of the coactivator protein. Because Gsh-1 is found to be expressed in the hypothalamus of the adult rat, our data provide evidence that the Gsh-1 homeobox protein plays a key role in the expression of the GHRH gene.
We report a case of chronic gastric volvulus in which ultrasonography (US) was useful. An 81-year-old woman was hospitalized due to vomiting, and upper gastroduodenoscopy revealed that the stomach was spirally twisted and constricted. An upper gastrointestinal barium study demonstrated an organoaxial-mesenteroaxial combined type gastric volvulus. US showed constriction between the dilated upper stomach body and the lower stomach body similar to a "peanut". Thereafter, the patient's vomiting stopped and follow-up US demonstrated that the constriction of the stomach was loosened. Therefore, we believe that this characteristic US sign paralleled the symptoms of the patient.
The present study was undertaken to evaluate the clinical applicability of cast CP titanium crowns fabricated with sintered molds. To this end, the dimensional changes and accuracy of fit of cast CP titanium crowns, manufactured under varying mold firing temperatures, were examined. Molds were fired at 7 temperatures. The outer height of the crown and outer width of the occlusal surface decreased under all sets of firing conditions. The outer width of the cervical part tended to increase at firing temperatures of 1,200, 1,300 and 1,400 degrees C. The inner widths of the occlusal surface and cervical part tended to increase under all sets of firing conditions. In the analysis of the fit of crowns, floating (gained latitude) was observed under all sets of conditions. However, the amount of floating was significantly smaller when the firing temperature was 1,200, 1,300 or 1,400 degrees C than when it was 800, 900, 1,000 or 1,100 degrees C.
We encountered a rare case of pulmonary granulomatous lesion accompanied with severe chest pain and hemoptysis. A 42-year-old man visited our hospital complaining of hemosputum. A chest radiograph showed a nodular shadow in the left lower lung field. Further examinations including fiberoptic bronchoscopy, bronchoalveolar lavage and transbronchial lung biopsy did not suggest a diagnosis. During the course of his illness, he suffered an episode of severe chest pain which could be controlled only by intravenous morphine chloride (10 mg). The chest radiograph at the time showed a broad infiltration in the left lower lung field. However, the lung perfusion scintigram taken 2 days before demonstrated decreased blood flow in the same field. We waited for the infiltration in the chest radiograph to diminish and then performed partial resection of the left lower lobe, thus terminating both hemosputum and chest pain. Histological examination showed a cavitary lesion in the periphery of the lung, surrounded by large numbers of infiltrating plasma cells and lymphocytes, among which were many hemosiderinladen macrophages. A small amount of mycelium, considered to be Nocardia or fungus, was seen in the cavity wall. These findings may indicate that an infection had contributed to the formation of a hemorrhagic granulomatous lesion, and that this lesion caused chest pain mainly because of the pleuritis and the decrease in the local pulmonary circulation.
BACKGROUND: There is no effective treatment for intractable postherpetic neuralgia. Because there is evidence that postherpetic neuralgia has an inflammatory component, we assessed treatment with intrathecally administered methylprednisolone to reduce pain in patients with this disorder. METHODS: We enrolled 277 patients who had had intractable postherpetic neuralgia for at least one year, 270 of whom were followed for two years. The patients were randomly assigned to receive intrathecal methylprednisolone and lidocaine (3 ml of 3 percent lidocaine with 60 mg of methylprednisolone acetate, 89 patients), lidocaine alone (3 ml of 3 percent lidocaine, 91 patients), or no treatment (90 patients) once per week for up to four weeks. Each weekly dose was injected into the lumbar intrathecal space. Pain was evaluated before randomization, at the end of the treatment period, and then four weeks, one year, and two years later. Samples of cerebrospinal fluid were obtained for measurement of interleukin-8 before and at the end of the treatment period. RESULTS: There was minimal change in the degree of pain in the lidocaine-only and control groups during and after the treatment period. In the methylprednisolone-lidocaine group, the intensity and area of pain decreased, and the use of the nonsteroidal antiinflammatory drug diclofenac declined by more than 70 percent four weeks after the end of treatment. No complications related to intrathecal methylprednisolone were observed. Before treatment, the concentrations of interleukin-8 in the cerebrospinal fluid were inversely related to the duration of neuralgia in all the patients (r=-0.49, P<0.001). In the patients who received methylprednisolone, interleukin-8 concentrations decreased by 50 percent, and this decrease correlated with the duration of neuralgia and with the extent of global pain relief (P<0.001 for both comparisons). CONCLUSIONS: The results of this trial indicate that the intrathecal administration of methylprednisolone is an effective treatment for postherpetic neuralgia.
Interleukin-18 (IL-18) is a recently discovered proinflammatory cytokine which plays a pivotal role in T helper 1 (Th1) responses. IL-18 is produced by macrophage-like cells, and inappropriate IL-18 production has been known to be involved in immunological disturbances. Schizophrenia is a common disease whose pathogenesis is still unclear; however, an activation of the inflammatory response system, including the Th1 cytokine response, may be related to the pathophysiology of schizophrenia. We measured the serum IL-18 levels of 66 schizophrenics and age- and sex-matched control subjects by using an ELISA assay. We found significantly increased serum IL-18 levels in the schizophrenic patients (P=0.0002). This finding supports the hypothesis that immune activation is involved in the pathophysiology of schizophrenia.