A novel screen for the detection of chitin acting antifungal compounds.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to T Sakurai.
Explore the source record for details and available documents.
To investigate the safety of rapid infusion of alendronate, we used alendronate therapy for 11 breast cancer patients with bone metastasis. Of the 11 patients, only 1 had hypercalcemia and the remaining 10 normocalcemia. Rapid infusion of alendronate consisted of an administration of alendronate 10 mg diluted in 100 ml saline in 30 minutes, and was repeated every two weeks. Each patient underwent 1 to 9 alendronate treatments. During alendronate therapy, only one patient complained of general fatigue, and the remaining 10 showed no alendronate-induced clinical symptoms. Rapid infusion of alendronate caused an increase in BUN level in two patients receiving intravenous hyperalimentation (IVH), a mild increase of GOT level in one, and a decrease of serum phosphorus level in two receiving IVH. However, no increase was found in serum creatinine and GOT levels. In addition, no patients showed alendronate-induced hypocalcemia. In conclusion, rapid infusion of alendronate brings about no major adverse effects, and makes it easier for many patients with bone metastasis to receive alendronate therapy on an outpatient basis.
To evaluate the efficacy of docetaxel therapy against anthracycline-resistant breast cancer, twenty patients were treated with docetaxel. Of the 20 patients pretreated with anthracycline, 17 were clinically anthracycline-resistant and the remaining three were refractory to anthracycline on histoculture drug response assay. Nine patients had loco-regional recurrence and 11 had distant +/- loco-regional recurrence. Docetaxel (49-60 mg/m2) was administered every 4 weeks, and was infused 1-13 times (median; 3 times). Of the 19 evaluable patients, eight (42%) showed partial response with the docetaxel therapy. Durations of the response ranged from 1 to 8 months (median; 4 months). Major adverse effects of the therapy were alopecia, neutropenia, and leucocytopenia. Hypersensitivity reaction was observed in one case. In addition, severe adverse effects such as grade 2 pneumonia and grade 4 diarrhea were found in one patient each. In conclusion, although the adverse effects are not negligible, docetaxel therapy is effective against anthracycline-resistant breast cancer.
Explore the source record for details and available documents.
The vascular system can be evaluated with computed tomography (CT), magnetic resonance angiography (MRA), angiography, and computer-based CT image processing systems before successful transluminally placed endovascular grafting (TPEG). Noninvasive modalities are useful, but angiography is mandatory to determine whether TPEG is indicated. During the procedure, fluorography with a wide-image intensifier and high-resolution digital subtraction angiography are known to be essential, but intravascular ultrasonography is also indispensable to achieve accurate TPEG.
In recent years, chronic massive pleural effusions have been increasingly recognized as a serious complication of pancreatitis. We describe the third reported case of a pancreatic pleural effusion accompanied by bronchopleural fistula. A 49-year-old man suffering from chronic alcohol-related pancreatitis was admitted to our hospital complaining of cough and shortness of breath. A chest x-ray film disclosed a large right pleural effusion with an air-fluid level. Ultrasonography and computed tomography of the upper abdomen demonstrated a giant pancreatic pseudocyst in the pancreatic tail and a fistulous tract reaching into the posterior mediastinum via the esophageal hiatus. Thoracentesis revealed sterile hemorrhagic fluid with markedly elevated amylase activity of 20,955 IU/l (pancreatic isozyme, 100%) and no malignant cells. A diagnosis of pancreatic pleural effusion was made. The therapy for pancreatic internal fistula is somewhat controversial. We employed conservative therapy, including hyperalimentation and chest tube drainage that successfully decreased the pleural effusion and closed the fistulous tract. Nonetheless, we were still troubled by a continuous air-leak via the drainage tube. Pleurodesis confirmed the tentative diagnosis of bronchopleural fistula and successfully stopped the air-leak. No re-accumulation of pleural effusion has been seen for 2 years. We concluded that pancreatic enzyme-rich effusions, if long-standing, may be complicated by bronchopleural fistula, thus underscoring the need for urgent drainage and initially conservative management.
A 65-year-old woman underwent radical operation for breast cancer in December, 1992. Between September, 1994 and January, 1997, she developed local recurrences four times as well as a supraclavicular lymph node recurrence. Each recurrence was treated with surgery and various types of chemoendocrine therapy, including anthracycline-containing chemotherapy. In April, 1997, she had developed a liver metastasis, which showed a partial response to docetaxel therapy. However, she developed a bone metastasis in January, 1998 (9 months after the initiation of docetaxel therapy). In addition to the docetaxel therapy, she was treated with a potent bisphosphonate, alendronate, 10 mg of which was infused every two weeks. Eight alendronate infusions resulted in a marked improvement in the bone metastasis, and the liver metastasis has been in regression for 13 months in response to the docetaxel therapy. In conclusion, alendronate is a promising agent against bone metastases which occur during docetaxel therapy for breast cancer.
To assess the safety of rapid infusion of incadronate and its efficacy against bone metastasis of breast cancer, we conducted a trial using incadronate therapy for breast cancer patients with bone metastasis. Of the 12 patients, 6 had undergone pamidronate or alendronate therapy. Rapid infusion of incadronate consisted of administration of 10 mg incadronate diluted in 100 ml saline in 30 minutes, and was repeated every two weeks. Each patient underwent 2 to 20 incadronate administrations. With the incadronate therapy, no patients showed hypocalcemia, but 3 patients showed asymptomatic hypophosphoremia. Of the 11 patients with bone pain, 5 patients (45%) experienced pain relief. A decrease in tumor marker levels in serum was found in 5 (56%) of the 9 patients with elevated marker levels. The side effects of incadronate administration were general fatigue (25%), pyrexia (17%) and transient pain increase (17%), but no renal dysfunction was found. In conclusion, rapid infusion of incadronate was a safe treatment and the incadronate therapy was effective against bone metastasis of breast cancer.
A 52-year-old woman with painful osteoblastic bone metastasis received pamidronate therapy which resulted in marked pain relief with a normalization of elevated tumor marker levels. However, the patient complained of increased pain after the 26th pamidronate infusion. Although a change from pamidronate to alendronate therapy did not relieve bone pain, a second change from alendronate to incadronate therapy resulted in pain relief with a decrease in re-elevated tumor marker levels. These findings suggest that bisphosphonate therapy is effective against osteoblastic bone metastasis in breast cancer, and that sequential therapy with bisphosphonates may be effective against bone metastasis in some cases.
To evaluate the significance of peptide leukotrienes in children with atopic dermatitis, we measured urinary LTE4 levels which are thought to reflect in vivo production of peptide LTs. Urine was collected in the early morning. There was no significant difference in urinary LTE4 levels among atopic children with different severities. On the other hand, urinary LTE4 levels were significantly elevated in the patients who had severe nocturnal itches compared with the patients who had mild nocturnal itches and normal controls. These results suggested that increased production of peptide LTs may be relevant to nocturnal itch of atopic dermatitis.
PURPOSE: To identify the integrated impact of psychological, social, and clinical factors onto the quality of life (QOL) in the patients with Crohn's disease. SUBJECTS AND METHODS: Two hundred twenty two out-patients participated in a cross-sectional questionnaire survey in which health-related QOL (SF36), disease-specific symptoms, psychological adaptation and social support were measured. Multi-variable regression models were used to test the impact of clinical, psychological, and social factors on the patient's QOL and symptom reports. RESULTS: The patient's symptoms and health-related QOL were significantly associated not only with disease activities, but also with the patient's psychological adaptation and the quality of social support. CONCLUSION: The results strongly suggest that a psychoeducational intervention may be useful in combination with a clinical intervention to improve the patient's QOL.
A 66-year-old woman had been treated for 3 years by her local physician with Sho-saiko-to for chronic hepatitis C virus (HCV) infection and liver cirrhosis. She was admitted to our hospital because of cough, fever, and infiltrative shadows on chest x-ray films. Sho-saiko-to-induced pneumonitis was diagnosed and steroid therapy started. Though a temporary improvement was observed, interstitial pneumonitis relapsed and the patient died of respiratory failure and liver dysfunction. Autopsy findings showed diffuse alveolar damage and honeycombing. Furthermore, reverse-transcriptase polymerase chain reaction techniques detected HCV-RNA in specimens of fibrotic lung tissue. For comparison, HCV-RNA was not histologically detected in lung tissue specimens from 4 control subjects who were positive for HCV antibodies but who did not have interstitial lung disease. It was speculated that the progression of interstitial pneumonia in the present case may have been caused by HCV in combination with Sho-saiko-to-induced lung injury.
Recent studies have identified several neuropeptide systems in the hypothalamus that are critical in the regulation of body weight. The lateral hypothalamic area (LHA) has long been considered essential in regulating food intake and body weight. Two neuropeptides, melanin-concentrating hormone (MCH) and the orexins (ORX), are localized in the LHA and provide diffuse innervation of the neuraxis, including monosynaptic projections to the cerebral cortex and autonomic preganglionic neurons. Therefore, MCH and ORX neurons may regulate both cognitive and autonomic aspects of food intake and body weight regulation. The arcuate nucleus also is critical in the regulation of body weight, because it contains neurons that express leptin receptors, neuropeptide Y (NPY), alpha-melanin-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP). In this study, we examined the relationships of these peptidergic systems by using dual-label immunohistochemistry or in situ hybridization in rat, mouse, and human brains. In the normal rat, mouse, and human brain, ORX and MCH neurons make up segregated populations. In addition, we found that AgRP- and NPY-immunoreactive neurons are present in the medial division of the human arcuate nucleus, whereas alpha-MSH-immunoreactive neurons are found in the lateral arcuate nucleus. In humans, AgRP projections were widespread in the hypothalamus, but they were especially dense in the paraventricular nucleus and the perifornical area. Moreover, in both rat and human, MCH and ORX neurons receive innervation from NPY-, AgRP-, and alpha-MSH-immunoreactive fibers. Projections from populations of leptin-responsive neurons in the mediobasal hypothalamus to MCH and ORX cells in the LHA may link peripheral metabolic cues with the cortical mantle and may play a critical role in the regulation of feeding behavior and body weight.
Rat C6 glioma is a cell line that has been used extensively as a model of astroglia. Although this cell line retains many of the properties of developing glia, it does not resemble morphologically the specialized form of glia found embryonically, the radial glia. In experiments designed to study a mutant form of receptor protein tyrosine phosphatase beta, we isolated a subclone of C6 called C6-R which, like radial glia, assumes a highly polarized radial-like morphology in culture. C6-R cells and, to a somewhat lesser extent, C6 cells, express cytoskeletal proteins found in developing astroglia including glial fibrillary acidic protein and RC1. As seen with radial glia, cerebellar granule cell bodies and neurites migrated along radial processes of C6-R cells in culture. Morphological analysis of dye-labeled cells injected into the developing forebrain revealed that a large fraction (approximately 60%) of the C6-R cells in the cortex assumed a radial orientation and about half of these (approximately 30%) made contact with the pial surface. In contrast, the parental C6 cells generally formed aggregates and only displayed a radial alignment when associated with blood vessels. These results suggest that we have generated a stable cell line from C6 glioma which has adopted certain key features of radial glia, including the ability to promote neuronal migration in culture and integrate radially in vivo in response to local cues. This cell line may be particularly useful for studying receptors on radial glia that mediate neuronal migration.
Reactions of Paracoccus halodenitrificans nitric oxide reductase (NOR) containing four iron centers, a low spin hemec, a low spin heme b, a high spin heme b and a non-heme iron, have been studied to show the roles of each iron center. Soon after reacting the resting (oxidized) NOR with L-ascorbate, the low spin heme c and low spin heme b were reduced to a considerable extent but the high spin heme b was still in the oxidized form and was reduced slowly. When CO acted on the reduced NOR, the high spin heme b center changed to a low spin state. On the other hand, when NO acted on the resting NOR, no apparent spectral change was observed. However, when NO acted on the reduced NOR (a steady state condition, excess dithionite is present), both of the low spin centers changed to be partly in the oxidized form. A small but clear new EPR signal with g = 4.1 appeared together with some new signals at the g = 2 region soon after the action of NO on the reduced NOR. During incubation at room temperature the nitrosyl-heme signal typical of 5-coordination developed. These results suggested that both the high spin-heme b center and the non-heme iron are the reaction centers and their reductions are indispensable for the enzyme process in contrast to the reaction mechanism proposed for the P-450 type NOR(P-450nor).
We determined the effect of nefiracetam, a novel cognitive enhancer, on the extracellular acetylcholine (ACh) level in the frontal cortex of freely moving rats, using a microdialysis technique without an acetylcholinesterase inhibitor in the perfusate. Treatment with nefiracetam (10 mg/kg, p.o.) produced a significant increase in the level of ACh in the brain dialysate, compared with the vehicle-treated group. This enhancing effect was also observed when the ACh level was elevated by administration of scopolamine (1 mg/kg, i.p.) at 45 min after the treatment with nefiracetam. In addition, perfusion of nefiracetam at the concentration of 10 microM significantly increased the extracellular ACh level in the frontal cortex of basal forebrain (BF)-lesioned rats, in which a marked decrease of the basal ACh level was observed in this region. These results suggest that enhancement of cortical ACh release by nefiracetam may contribute to an anti-amnesic effect on the learning deficits induced by treatment of scopolamine or BF-lesion in rats.
The trinuclear centers in Rhus vernicifera laccase and Cucumis sativus ascorbate oxidase have been studied by EPR spectroscopy and magnetic susceptibility measurements over the wide range of 5 K to 300 K. The EPR spectra showed that type II copper receives increasing tetrahedral distortion with raising temperature. Magnetic susceptibilities of laccase showed that both of type I and type II coppers are almost fully paramagnetic since the antiferromagnetic interaction between type III coppers is extremely strong from 5 K to 300 K. On the other hand, the effective magnetic moment of ascorbate oxidase is contributed by ca. 1.7 Cu2+ even below ca. 100 K, since type II Cu is partly in the reduced form. The effective magnetic moment continuously increased with raising temperature because the antiferromagnetic interaction between type III coppers is not as strong as in the case of laccase. The simulation of the SQUID measurement results suggested that the conformational change of the ascorbate oxidase molecule caused the temperature dependence of the antiferromagnetic interaction. The type II Cu EPR signals in laccase and ascorbate oxidase were conspicuously broadened with raising temperature because of the increasing contribution of the triplet state by type III Cu's and/or of the rapid relaxation which finally led to only ca. 30% detection of the type II Cu signals at room temperature. The stepwise binding of azide to the trinuclear center made one of type III Cu's to be EPR detectable. SQUID measurements indicated that only one Cu in the trinuclear center is paramagnetic and other two Cu's are antiferromagnetically coupled for both of the one- and two-azide bound forms. The binding mode of azide to the trinuclear center was discussed based on some models.
Endothelin 3 (EDN 3) and the endothelin receptor B (EDNRB) are involved in the development of neural crest and particularly of the melanocytes and the enteric nervous system. We reported previously that the avian EDNRB gene is expressed in the neural fold before crest cell migration and later on in all the neural crest derivatives except, at any developmental stage, in the melanocytic lineage. However, quail melanoblasts proliferate in response to EDN 3 stimulation in vitro. These observations prompted us to search for another type of endothelin receptor (EDNR). We report here the cloning by reverse transcriptase-PCR of an avian cDNA encoding a subtype of EDNR, which we have called EDNRB2, because its deduced amino acid sequence is more closely related to that of EDNRB than to either the mammalian EDNRA or to the Xenopus EDNRC. Its expression pattern differs from that of the "classical" avian EDNRB because it is strongly expressed in melanoblasts and melanocytes. EDNRB2 transcripts are also abundant in the liver and kidney. Our pharmacological studies showed that EDNRB2 binds with similar affinity to EDN 1, EDN 2, and EDN 3, further confirming that this receptor belongs to the B type, although it displays a low affinity for sarafotoxin-c, a known EDNRB-selective agonist.