Umpolung of vinyloxiranes: regio- and stereoselectivity of the In/Pd-mediated allylation of carbonyl compounds.
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Journal Article↗
Biomedical subjects
K Kameda
Publications and source records attributed to K Kameda.
The role of intracellular Ca(2+) in apoptosis induced by hyperthermia and its enhancement by verapamil in U937 cells.
PURPOSE: The relationship between apoptosis induced by 42 degrees C and 44 degrees C hyperthermia alone or in combination with verapamil and changes in intracellular Ca(2+) concentration ([Ca(2+)]i) was investigated in U937 cells. METHODS: Apoptosis induced by hyperthermia was assessed according to DNA fragmentation, nuclear morphologic changes, and expression of phosphatidylserine on the outside plasma cell membrane. These changes were measured by flow cytometry. The [Ca(2+)]i of individual cells after hyperthermia was monitored by a digital image-analyzing technique using Fura-2. RESULTS: Hyperthermia-induced apoptosis reached a plateau after 6 h and was found to be both time and temperature-dependent. DNA fragmentation was maximum at 44 degrees C after 30 min. Verapamil enhanced the apoptosis induced by 42 degrees C and 44 degrees C hyperthermia in normal cells and by 44 degrees C hyperthermia in thermotolerant cells. The number of cells containing higher [Ca(2+)]i (more than 200 nM) was significantly increased by hyperthermia and further elevated by the addition of verapamil in both normal and thermotolerant cells. Apoptosis induced by hyperthermia was markedly decreased by an intracellular Ca(2+) chelator, BAPTA-AM, in a dose-dependent manner. CONCLUSION: These results indicate that [Ca(2+)]i increase plays a crucial role in apoptosis induced by hyperthermia and the combined treatment with verapamil in normal and thermotolerant U937 cells. Furthermore, hyperthermia-combined drug therapy has potential significance in cancer therapy.
Apoptosis↗
Effects of lithium on dopamine D2 receptor expression in the rat brain striatum.
Effects of lithium on the dopamine D2 receptor expression in the rat brain striatum were studied. Feeding the chow containing 0.2% LiCO3 for 6 days increased the level of the dopamine D2 receptor mRNA, and the transcription rate of the dopamine D2 receptor gene, indicating the stimulatory effects of lithium on the transcription of the dopamine D2 receptor gene. [3H] Spiperone binding to the striatal membranes increased in the rats treated with lithium, while the Western blotting analysis showed no change of the amount of the dopamine D2 receptors. These results suggested that lithium might induce the conformational changes of the dopamine D2 receptors. The methamphetamine-induced locomotor activity was enhanced by the pretreatment with lithium, whereas simultaneous increase in the methamphetamine concentration in the striatum was also observed. These observations suggested that the stimulation of methamphetamine-induced locomotor activity by lithium might be, at least partly, due to either increased sensitivity of the dopamine receptors, or increased concentration of methamphetamine in brain, or combination of both.
Animals↗
Effects of acute citalopram treatment on the methamphetamine-induced locomotor activity.
1. Previously the authors have shown that acute citalopram treatment increased the dopamine D2 receptor expression in rat brain striatum (Kameda et al., 2000). In the present study, the authors attempted to determine whether these effects of citalopram influence the methamphetamine-induced locomotor activity. 2. The pretreatment with a single administration of citalopram (10 mg/kg, i.p.) resulted in the significant enhancement of the locomoter activity induced by methamphetamine treatment (1 mg/kg, i.p.). The enhancement was observed 30 min, 12 hours, 24 hours, but not 7 days after withdrawal of citalopram administration. 3. Then the authors determined the methamphetamine concentration in rat brain striatum by gas chromatography-mass spectrometry (GC-MS) The results showed that the concentration of methamphetamine wars significantly higher in the rats 24 hours, and also 7 days after withdrawal of citalopram administration, compared to the control rats. 4. These results emphasized the involvement of the high methamphetamine concentration, caused by the pretreatment with citalopram, in the enhancement of the methamphetamine-induced locomotor activity. However high methamphetamine concentration alone could not account for this enhancement, since the high concentration of methamphetamine observed 7 days after withdrawal of citalopram administration did not appear to enhance the methamphetamine-induced locomotor activity. Another mechanism through which the pretreatment with citalopram enhanced the methamphetamine-induced locomotor activity, such as the increased expression of the dopamine D2 receptors, could not be excluded.
Animals↗
Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells.
Norepinephrine induced lipolysis in rat fat cells, in vitro, in a time- and concentration-dependent manner, without concomitantly increasing hormone-sensitive lipase (HSL) activity. It also induced, time and concentration dependently, HSL translocation from the cytosol to the lipid droplets in fat cells. Isoproterenol, forskolin, dibutyryl cyclic AMP, and theophylline also induced lipolysis in fat cells, but did not stimulate HSL activity. These agents also induced HSL translocation from the cytosol to the lipid droplets in fat cells: about 80% to 90% of all HSL was located in lipid droplets after incubation for 1 h. These results suggest that the critical event in lipolytic activation of fat cells induced by lipolytic agents is not an increase in the catalytic activity of HSL but translocation of HSL to its substrate on the surfaces of lipid droplets in fat cells.-Morimoto, C., K. Kameda, T. Tsujita, and H. Okuda. Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells. J. Lipid Res. 2001. 42: 120;-127.
Adipocytes↗
[A case of breast cancer with bone marrow and liver metastases responding completely to low-dose weekly paclitaxel combined with toremifene].
A 36-year-old woman was admitted to our hospital because of general malaise in October 1999. She was diagnosed with bilateral breast cancer with bone marrow and liver metastases. Low-dose weekly paclitaxel (60 mg/body/week) combined with toremifene (120 mg/day) was started in December 1999. Myelofunction was recovered after 2 weeks of chemotherapy (CT), and the primary tumors and cervical/axillary lymphadenopathy disappeared after 4 weeks of CT. Bone marrow and liver metastases was no longer detected after 16 weeks of CT, and the case was evaluated as a complete response (CR). The same therapy has been performed for eight months and no evidence of recurrence has been observed.
Adult↗
Direct interaction of actin with p47(phox) of neutrophil NADPH oxidase.
The cell-free activation of human neutrophil NADPH oxidase is enhanced by actin, and actin filaments formed during activation are suggested to stabilize the oxidase. In an attempt to elucidate the mechanism, we examined the protein-protein interactions between actin and cytosolic components of the oxidase. Far-Western blotting using recombinant phox proteins showed that both alpha- and beta-actin interacted with p47(phox) and rac1, and weakly with rac2. A deletion mutant of p47(phox) proved that its C-terminal region was essential for the interaction. The dissociation constant (K(d)) for interaction between actin and p47(phox) was estimated to be 0.45 microM by surface plasmon resonance, and that between actin and rac1 or rac2 was 1.7 or 4.6 microM, respectively. Far-Western blotting using cytosol as a target showed an interaction between actin and endogenous p47(phox) and rac proteins. These results suggest that actin can directly interact with p47(phox) and possibly with rac in the cells.
Actins↗
Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D2 and serotonin 5-HT2A receptors in the rat brain.
The effects of 3-week treatment with a typical antipsychotic drug chlorpromazine and three atypical antipsychotic drugs (risperidone, olanzapine and perospirone) on the binding to dopamine D2 and serotonin 5-HT2A receptors were examined in the rat stratum and frontal cortex, respectively. Subchronic treatment with chlorpromazine (10 mg/kg) and perospirone (1 mg/kg) significantly increased D2 receptors, while no increase was observed with lower dose of chlorpromazine (5 mg/kg), perospirone (0.1 mg/kg), risperidone (0.25, 0.5 mg/kg) or olanzapine (1, 2 mg/kg). On the other hand, 3-week administration of chlorpromazine (5, 10 mg/kg) and olanzapine (1, 2 mg/kg) significantly decreased 5-HT2A receptors, but risperidone (0.25, 0.5 mg/kg) or perospirone (0.1, 1 mg/kg) had no effect. The measurement of in vivo drug occupation for D2 and 5-HT2A receptors using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) suggested that high occupation of 5-HT2A receptors with lower D2 receptor occupancy might be involved in the absence of up-regulation of D2 receptors after subchronic treatment with some atypical antipsychotic drugs.
Animals↗
Contribution of each caffeoyl residue of the pigment molecule of gentiodelphin to blue color development.
To clarify the function of each caffeoyl residue in the diacylated anthocyanin gentiodelphin, a pigment from the blue flower of Gentiana makinoi, two mono-deacyl derivatives were compared for both color development and stability. In neutral solution, 3,5-di-O-beta-D-glucopyranosyl-3'-O-(6-O-caffeoyl-beta-D- glucopyranosyl)delphinidin was both bluer and more stable than 3,3'-di-O-beta-D-glucopyranosyl-5-O-(6-O-caffeoyl-beta-D- glucopyranosyl)delphinidin. Conformational analysis of each derivative under acidic conditions revealed only the 3'-O-caffeoylglucopyranosyl derivative to demonstrate intramolecular stacking. Additionally, the acyl residue in the B-ring contributed more to blue color development than that in the A-ring.
Acylation↗
Treatment response in depressed patients with enhanced Ca mobilization stimulated by serotonin.
Serotonin (5-HT)-stimulated intraplatelet calcium (Ca) mobilization has been shown to be enhanced in nonmedicated depressive patients by many studies. However, there has not been any longitudinal follow-up study of this parameter. We examined the relationship between treatment response and pretreatment value of the 5-HT-induced Ca response. The 5-HT(10 microM)-induced intraplatelet Ca mobilization was measured in 98 nonmedicated depressive patients (24 bipolar disorders, 51 melancholic major depressive disorders, and 23 non-melancholic major depressive disorders). These patients were followed up prospectively for a further period of five years. The depressed patients with enhanced Ca response to 5-HT in bipolar disorders exhibited a good response to mood stabilizers but those with major depressive disorders showed a poor response to antidepressants. These findings suggest the possibility that the 5-HT-induced intraplatelet Ca response may be a good predictor of treatment response in depressed patients. Longer longitudinal follow-up studies are needed in larger samples to examine if this parameter may be a specific biological marker for unipolar-bipolar dichotomy.
Adult↗
The activity of fatty acid synthase of epidermal keratinocytes is regulated in the lower stratum spinousum and the stratum basale by local inflammation rather than by circulating hormones.
The epidermal keratinocytes produce and secrete lipids to maintain the water barrier of the epidermis. To clarify the regulation of epidermal lipid synthesis, we investigated the hormonal effect on the activity of fatty acid synthase (FAS) of the keratinocytes, and the expression of FAS in the human skin. In cultured keratinocytes, the FAS activity, assayed by measuring the oxidation of NADPH, was slightly increased by hydrocortisone or testosterone, but not influenced by thyroid hormone, estrogen, progesterone or insulin. In immunohistochemical study of normal human epidermis, FAS was expressed strongly in the stratum granulosum and moderately in the uppermost layer of the stratum spinousum (SS), suggesting that fatty acid synthesis may increase during normal epidermal differentiation. In inflammatory disorders, such as psoriasis, lichen planus, and atopic dermatitis, FAS was also expressed in the lower SS and the stratum basale (SB), resulting in strong staining in the whole layers of the epidermis. Remarkable increase of FAS expression was only observed in the lower SS and the SB. Therefore, the activity of FAS in the epidermis may be regulated in the lower SS and the SB by local inflammation rather than by circulating hormones. In other components of the skin, FAS was strongly expressed not only in adipose tissue and sebaceous glands, which are known as active sites of lipid synthesis, but also in sweat glands, suggesting that the sweat glands can synthesize abundant fatty acids de novo.
Antibodies↗
Mechanism of the stimulatory action of okadaic acid on lipolysis in rat fat cells.
Okadaic acid was found to induce concentration- and time-dependent lipolysis in rat fat cells in the absence of lipolytic hormones, but it did not significantly increase the total hormone-sensitive lipase (HSL) activity in these fat cells, the activity of HSL extracted from fat layer and that of HSL in the supernatant of homogenized fat cells. Western blotting of fat cell homogenate fractions with an antiserum raised against synthetic peptide derived from rat HSL showed that HSL protein shifted from the supernatant to the fat layer in response to okadaic acid, which increased the HSL protein content on the fat layer and concomitantly reduced that of the supernatant, concentration- and time-dependently. Sonication of the fat cells abolished their responsiveness to okadaic acid. The lipolytic action of okadaic acid was examined and its site was identified using a cell-free system comprising lipid droplets isolated from rat fat cells and HSL. Okadaic acid induced lipolysis in this cell-free system and sonication of the lipid droplets caused disappearance of lipolytic action of okadaic acid. Okadaic acid failed to stimulate lipolysis in a cell-free system comprising HSL and artificial lipid droplets (trioleoylglycerol emulsified with gum arabic) instead of lipid droplets isolated from rat fat cells. These results suggest that okadaic acid does not increase the catalytic activity of HSL but induces translocation of HSL to the lipid droplets isolated from rat fat cells. The site of the lipolytic action of okadaic acid in relation to the interaction between HSL and lipid droplet is discussed.
Adipocytes↗
[Thinking about tuberculosis in Osaka City].
The incidence rate of tuberculosis in Osaka City (104.2 per 100,000 population) is extremely high, namely 3 times higher than the national average. Why the tuberculosis situation of Osaka City is so bad? The reason could be summarized as follows: Before the end of the World War II (1945), it was the sequelae of high prevalence observed in the era of Meiji, Taisho and early years of Showa. However, after the World War II, especially from the Heisei era (1989-), it is deeply affected by the influence of socio-economic background in Japan. Osaka City is characterized as the city of merchants and small enterprises. And therefore, the city substantially has the nature of the locality that brings in or produces some kinds of social vulnerability such as temporary laborers and homeless people. Of the tuberculosis patients in Osaka City, about 20% are homeless. In addition, patients of the smear positive infectious tuberculosis are often discovered among temporary laborers who change their residences and job sites from place to place and contact widely with citizens. These two are the most difficult problems in tuberculosis control program of Osaka City. In the meantime, there are many citizens who are careless of their health and do not follow the law or social rule, and this has apparently no direct connection with the problems of tuberculosis. However, it might be one of the factors of an undesirable trend of tuberculosis in Osaka City. In order to improve such a unfavorable tuberculosis situation in Osaka City, effective and strong supporting activities to the tuberculosis program are essentially needed. And these activities must be done from the standpoint of health-promotion, namely, health education for citizens and improvement of social environmental conditions to maintain healthy and cultural life.
Health Education↗
Expression of highly polysialylated neural cell adhesion molecule in pancreatic cancer neural invasive lesion.
Neurotropism of pancreatic cancer is one of the hypotheses explaining neural invasion, which is one of the characteristics of pancreatic cancer. In these studies, we immunohistochemically examined neural cell adhesion molecules (NCAM), homophilic adhesion molecules expressed on the nerve cells, as a factor of neurotropism, in 15 pancreatic cancer operatively obtained, especially in neural invasive lesions. We also investigated the role of polysialic acid (PSA), which is attached to NCAM and related to the malignant potential of cancers. NCAM was detected in 66.7% of pancreatic cancers, and in all 9 cases with massive perineural invasion. In neural invasive lesions, however, there were perineurium and endoneurium, which do not express NCAM, between the cancer and nerve cells. PSA was also detected in the pancreatic cancers expressing NCAM. Moreover, PSA expression was stronger in the perineural invasive lesions than in the main tumor and was related to the cancer cell proliferation investigated by Ki-67 staining. It is unlikely therefore, that NCAM plays an important role in neurotropism. However, the NCAM expressed on the pancreatic cancer was attached to PSA, which itself plays an important role in the malignant potential of this disease.
Aged↗
Relationship between hormone-sensitive lipolysis and lipase activity in rat fat cells.
An assay for total hormone-sensitive lipase (HSL) in rat fat cells was devised in which fat-associated HSL was solubilized with ether, and triolein or cholesteryloleate was used as substrate. Norepinephrine (NE) caused marked release of glycerol from fat cells but did not activate HSL as estimated using triolein or cholesteryloleate as substrate. Propranolol, a beta-blocker, inhibited NE-induced lipolysis in fat cells without a concomitant reduction in HSL activity. The antilipolytic action of insulin on NE-induced lipolysis could not be explained by a decrease in HSL activity. Neither ACTH-induced lipolysis in fat cells nor its inhibition by insulin was accompanied by matching fluctuations in HSL activity. These results indicate that neither NE and ACTH-induced lipolysis in fat cells, nor the antilipolytic actions of propranolol and insulin, involve fluctuations in HSL activity.
Adipocytes↗
Thallium-201 scintigraphy in malignant mesothelioma.
A patient with malignant pleural mesothelioma was investigated using 201Tl scintigraphy. There was diffuse pleural tumour accumulation on planar scintigraphy. Single photon emission computed tomography (SPECT) demonstrated exact tumour location. It is concluded that planar scintigraphy using 201Tl may be useful in detecting mesothelioma. Clearer tumour localization is possible with SPECT.
Female↗
[A case of valve-like structure in ureter associated with pyonephrosis due to Salmonella infection].
A 7-year-old boy had a fever of 39 degrees C. Abdominal computed tomography (CT) revealed marked left hydronephrosis with hydroureter. Percutaneous nephrostomy was performed. Salmonella infanitis was detected from the drainage urine. Cystourethrography after nephrostomy showed bilateral vesicoureteral reflex (VUR). On the left side, ureteropelvic junction (UPJ) stenosis was found. Left fistelography showed hydronephrosis, but the ureter was not visualized. A mechanism like a valve at the left UPJ was suggested; the bladder urine was able to ascend to the pelvis but not to be drained from the pelvis. The left renal function was not expected to recover from the findings of renal scintigram and CT. Left nephroureterectomy and right anti-VUR operation were performed. The extirpated renal and ureteral specimens revealed a nonpapillary tumorous structure like a valve at the left UPJ. The histological examination of the valve-like structure revealed the presence of two muscle layers without an adventitia folded at the UPJ.
Child↗
[The prevalence survey on chronic tuberculosis patients with bacilli discharge in Osaka prefecture].
This survey was made at the end of 1996 in Osaka prefecture including three ordinance designated cities of Osaka, Sakai and Higashiosaka. As of December 31 1996, 109 or 3.3% of active tuberculosis cases were found to be chronic tubercle bacilli excreters in Osaka city, and 128 or 3.6% in Osaka prefecture other than Osaka city, respectively. In the area called Airin at Nishinari-ward, Osaka, which has been an area with high prevalence of the disease, 33 or 5.8% were chronic tubercle bacilli excreters, and the rate was slightly higher than the other areas. Compared to the survey conducted 10 years ago, while the number of the chronic tubercle bacilli excreters decreased by half to 109 from 200 in Osaka city, to 128 from 211 in Osaka prefecture excluding Osaka city, the rate of chronic excreters to total active tuberculosis showed almost no change. Various factors such as difficult living conditions often attributed to defaulting of active tuberculosis patients from their treatment, thus resulting to development of chronic excretion. It is highly recommended to apply DOTS strategy for the completion of their treatment. Public health centers that have personal clinical records of each patient should be familiar with the results of their bacillus examinations. They should also be required to cooperate with medical institutions to cope with those who need retreatment.
Adult↗