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Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 631 records · Page 35Linked to original sources

[SLE with interstitial pneumonia during cyclophosphamide pulse therapy].

A 49 year-old man was admitted for edema and renal impairment due to SLE. Since he did not improve with predonisolone and methylprednisolone pulse therapy, cyclophosphamide pulse therapy (300 mg div.) was administered. The patient subsequently developed a fever, dyspnea and cough, and interstitial regions of the lungs exhibited shadows on X-ray and CT. The patient also suffered hypoxemia and poor lung function. Since several culture tests and viral antibody tests were negative for infection, antibiotics were not effective, and TBLB indicated interstitial pneumonia, which we speculated was induced by cyclophosphamide. However, this was such a severe case of interstitial pneumonia that it could not be cured merely by discontinuing the cyclophosphamide, but it did improve immediately after starting methylprednisolone pulse therapy. The incidence of cyclophosphamide-induced interstitial pneumonia is very low, but the mortality rate is high. Since cyclophosphamide pulse therapy is often used to treat SLE, attention should be focused on the incidence of interstitial pneumonia.

Cyclophosphamide↗

Effect of the angiotensin-converting enzyme inhibitor enalapril on post-transplant erythrocytosis.

Post-transplant erythrocytosis (PTE) is increasingly recognized as a complication of kidney transplantation. In this study we report the effect of the angiotesin-converting enzyme (ACE) inhibitor enalapril on hematocrit (Ht) and erythropoietin in four patients with PTE. Four renal allograft recipients with Ht greater than 51% were studied. Treatment was initiated with enalapril administered orally at a dose of 2.5 mg/day. All the patients had an increase of hemoglobin (Hb) (17.7 +/- 0.64 g/dl), Ht (54.5 +/- 1.29%) and red blood cell count (RBC) (584 +/- 19.2 x 10(4)/microliter). All patients responded to enalapril in 8 weeks with a significant decrease of Hb, Ht, and RBC. In one patient, the downward trend was more rapid and sustained, and treatment had to be discontinued to prevent the development of anemia. Serum erythropoietin showed normal in all four patients and remained unchanged during the study, even after discontinuation of enalapril treatment. Serum creatinine remained relatively stable throughout the study. These results suggest that PTE may not be dependent upon circulating erythropoietin and that enalapril treatment may be an effective treatment of PTE without renal dysfunction.

Adult↗

[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group].

We conducted multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days. In cervical cancer, 24 patients were enrolled and 17 of them were evaluated. The overall response rate including CR and PR was 23.5% (4/17). In ovarian cancer, 18 patients out of 21 enrolled were evaluated. The overall response rate was 16.7% (3/18). The primary toxicity observed was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were anorexia, nausea, vomitting, fatigue, alopecia and stomatitis. From these results we concluded that oral etoposide administered for 21 consecutive days was effective against cervical cancer.

Administration, Oral↗

[Evaluation of the effect of ischemic preconditioning using near-infrared spectroscopy].

Ischemic preconditioning (IP) protects the myocardium from subsequent sustained ischemic insults. Temporary occlusion of the coronary artery is indispensable for anastomosing the graft vessel during coronary artery bypass operation without cardiopulmonary bypass. In the canine model of ischemia and reperfusion, we measured myocardial tissue oxygen saturation (SO2) continuously using near-infrared spectroscopy to determine the effect of IP on myocardial oxygen metabolism. Nine dogs underwent occlusion of the left descending coronary artery for three 5-minute periods, followed by three 5-minute periods of reperfusion. The dogs were then subjected to a 20-minutes periods of sustained coronary artery occlusion, followed by prolonged reperfusion. The myocardial SO2 was 82 +/- 2% at the baseline before coronary occlusion and was decreased to 74 +/- 2%, 76 +/- 2%, 77 +/- 3%, 77 +/- 3% at the first, second, third and sustained coronary occlusion, respectively. The increase in the minimum myocardial SO2 value at the second and third coronary occlusion suggested the effect of IP. Near-infrared spectroscopy is a useful method of continuously monitoring myocardial oxygenation and of evaluating the effect of IP during off-pump heart surgery.

Animals↗

Accumulation of p300 mediates transcriptional repression of simian virus 40 enhancer in undifferentiated F9 embryonal carcinoma cells.

The SV40 enhancer is repressed in embryonal carcinoma (EC) cells, and it is also repressed by the adenovirus E1A oncoprotein. Repression by E1A is mediated by the binding of E1A to the p300 transcriptional coactivator. Thus, we examined the role of p300 in the repression of the SV40 enhancer activity in EC cells. We demonstrated that high levels of p300 protein are accumulated in undifferentiated EC cells and that the levels decline dramatically upon differentiation because of the changes of protein stability. Furthermore, we showed that overexpression of p300 does not stimulate the SV40 enhancer activity in undifferentiated F9 cells. However, the activity of a p300 mutant deficient for E1A binding can be restored by the presence of excess E1A. In addition, low-level expression of E1A causes derepression of the enhancer activity in F9 cells. These results indicate that the accumulation of p300 protein participates in repression of the SV40 enhancer activity in undifferentiated F9 cells.

Activating Transcription Factor 1↗

[Late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer. ETP 21 Study Group--Cervical Cancer Group].

We conducted a multi-site late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer in cooperation with 32 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Treatment cycles were to be repeated at 4- to 5-week intervals. Eighty patients were enrolled and 70 patients were evaluated. The overall response rate (95% CI), including one complete response patient and 18 partial response patients, was 27.1% (19/70). The most commonly observed toxicity was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were gastrointestinal toxicities such as anorexia, nausea, stomatitis and vomiting, as well as fatigue and alopecia. These adverse effects were well tolerated and controlled with medications. From these results we concluded oral etoposide administered for 21 consecutive days was an effective drug against cervical cancer.

Adenocarcinoma↗

[History of society for family group activity for patients receiving home visiting care].

We organized a society for the support of patients receiving home visiting care and their families in 1982. The group started with 13 members and now has more than fifty members. Some members a remain after the patients' death and give advice as alumni. The group was named "Kibo-no-kai" i.e., "hope". At first, the group was a place to complain about daily care and cheer one another up. But gradually, the demands for better welfare were occurred to the members, and we have made requests to the mayor. Since 1984 we had a talk with the mayor four times and obtained some improvements in welfare; for example, bath service for patients undergoing gastrostomy or tracheostomy, supply of paper diapers, simplification of welfare service procedures and so on. We meet 4 times a year, publish bulletins, and meet in small groups in each area occasionally. This paper reported the history of this group for 15 years.

Family↗

Prevalence of hepatitis B and C infection markers among adult women in urban and rural areas in Shaanxi Province, China.

In an attempt to investigate possible urban-rural difference in prevalence of hepatitis B and C virus (HBV and HCV, respectively) infection in continental China, triplet surveys on HBV and HCV infection markers (ie, HBsAg, anti-HBs, anti-HBc, and anti-HCV) and serum enzyme levels (AST, ALT and gamma-GTP) were conducted in 1997 on groups of apparently healthy adult women (49 to 50 subjects per group); one group (the City group) was in Xian, the provincial capital of Shaanxi Province, and two others (the Village A group and the Village B group) were in farming villages in the Province some 200 and 25 km away from Xian, respectively. Comparison among the three groups showed that there was no urban-rural difference in prevalence of HBV and HCV infection positive (HBV+ and HCV+) cases and that the overall prevalence of HBV+ and HCV+ cases was 70% and 3%, respectively. HBsAg+ prevalence was however higher in the villages (8% when the two villages were combined) than in the city (2%). HBV infection was not associated in general with apparent increase in emission enzyme levels in the serum, whereas HCV infection might be associated with an increase in ALT, AST and gamma-GTP. The present observation in combination with other previously published results suggests that urban-rural difference will not be remarkable in HBV and HCV infection prevalence in Continental China and that the public health problem is more serious with HBV infection and quite less so with HCV infection.

Adult↗

Mechanisms of IL-6, IL-8, and GM-CSF release in nasal secretions of allergic patients after nasal challenge.

Cytokines are potentially active biological peptides that are known to play an important role in several immune responses. Several studies have reported the existence of a variety of cytokines in the nasal mucosa of patients with allergic rhinitis. However, there are few reports on cytokines released into the nasal secretion. In the present study, we investigated the sources, and levels of three key proinflammatory cytokines namely, IL-6, IL-8, and GM-CSF in the nasal secretion, as well the mechanisms of their release, by ELISA and immunohistochemistry. Firstly, we examined the levels of IL-6, IL-8, and GM-CSF in the nasal secretion after in vivo nasal challenge with methacholine (MC), histamine (HI) and allergen (Ag) in patients with nasal allergy to house dust mite (HDMAR). Next, we examined the levels of IL-6, IL-8, and GM-CSF released, in vitro, after Ag challenge of nasal scrapings from patients with HDMAR. Finally, we examined the sources of these cytokines in the nasal mucosa, by immunohistochemistry. After MC challenge in patients with HDMAR, the concentration of IL-6, but not IL-8, and GM-CSF, was significantly greater on the challenged side than on the contralateral side. Ag and HI provocation induced significantly greater levels of IL-6 and IL-8 secretion in patients with HDMAR, on the challenged side than on the contralateral side. GM-CSF was only detected in the nasal secretion after Ag challenge. Immunoreactivity for IL-6 and IL-8 was very similar in that it was predominantly localised to the apical portion of epithelial cells, the superficial lamina propria, gland cells, and migrating cells. The immunoreactivity for GM-CSF varied slightly from that of IL-6 and IL-8: strong immunoreactivity was detected in the basal part of epithelial cells, basement membrane, glandular ducts, and migrating cells. These results suggest that the levels, sources, and mechanisms of release of IL-6, IL-8, and GM-CSF in the nasal secretion of patients with HDMAR do vary, but are important in the manifestation of the allergic reaction.

Animals↗

Gene expression of gonadotropin-releasing hormone, but not its receptor, in human endometrium and decidua.

Gonadotropin-releasing hormone (GnRH) has been reported to exist in extrahypothalamic tissues such as the placenta, gonads and mammary glands. While we have reported the presence of GnRH-mRNA in the rodent uterus, there have been no reports concerning gene expression of GnRH and its receptor (GnRH-R) in human endometrial tissue. In order to investigate the role of GnRH as a local regulator in the human endometrium, we examined the gene for GnRH and GnRH-R in non-pregnant endometrium and decidua of early pregnancy. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis we found GnRH-mRNA but not GnRH-R-mRNA transcripts in the human endometrium and decidua at 7-9 weeks gestation. This is the first report that suggests GnRH gene expression in the human endometrium/decidua.

Blotting, Southern↗

Maize and foxtail millet as substantial sources of dietary lead intake.

In 1996, 24-h food duplicate samples were collected from two groups of 50 non-smoking women each; one group was in Jinan, the capital city of Shandong Province in China, and the other in a farming village in the Zhangqiu area some 30 km away from the city. The people in the village took significantly more dietary lead (46 micrograms/day) than their counterparts in the city (26 micrograms/day), and blood lead concentrations (35 and 50 micrograms/l for the urban and the rural people, respectively) were in parallel with the dietary lead intake. Search for cereals as the determinants of dietary lead intake and blood lead concentration by multiple regression analysis showed that maize was the most influential source of dietary lead intake among the four common cereals of wheat, rice, foxtail millet (to be called just millet) and maize, whereas millet was the leading determinant of the blood lead level among the four cereals although the influential power was weaker than millet for dietary lead. Lead content in maize (47 ng/g) and millet (47 ng/g) was twice or even more times higher than the levels in wheat (26-30 ng/g) and rice (20-21 ng/g). The significant roles of non-rice/non-wheat cereals such as millet and maize as possible dietary lead sources for farming populations are discussed.

Adult↗

Cyclic strain stimulates isoform-specific PKC activation and translocation in cultured human keratinocytes.

Previous studies have demonstrated that cyclic strain induces keratinocyte proliferative and morphological changes. Since protein kinase C (PKC) is known to play an important role in the regulation of keratinocyte growth and differentiation, the objective of this study was to determine the role of the PKC signaling pathway as a mediator of strain modulation of the keratinocyte phenotype. In particular, we tested the following specific hypotheses: (1) cyclic strain stimulates PKC activity and translocation, (2) cyclic strain activates PKC in an isoform-specific manner, and (3) PKC mediates the strain activated proliferative and morphological response in cultured human keratinocytes. To test these hypotheses, keratinocytes were subjected to vacuum-generated cyclic strain (10% average strain), followed by measurement of PKC activity, PKC isoform distribution by Western blot analysis and confocal microscopy, and examination of the effect of PKC inhibitors (calphostin C and staurosporine) on strain induced proliferative and morphological changes. We observed stimulation of PKC activity (62.3 +/- 5.1% increase) coupled with translocation of PKC from the cytosolic to the membrane fraction in keratinocytes subjected to acute cyclic strain. Cyclic strain also caused translocation of PKC alpha and delta, but not zeta isoforms, from the cytosolic to the membrane fraction as demonstrated by both Western blot analysis and confocal microscopy. PKC beta was not detected in these cells. PKC inhibitors, calphostin C (10 nM), and staurosporine (5 nM), inhibited strain-induced PKC activation and keratinocyte proliferation, but did not block the effects of strain on cellular morphology or alignment. We conclude that these data support our hypothesis that cyclic strain stimulates PKC activity and translocation in an isoform-specific manner in cultured human keratinocytes. Moreover, our studies with PKC inhibitors support the hypothesis that strain-induced changes in the keratinocyte phenotype may be selectively modulated by PKC.

Biological Transport↗

A simple and sensitive bioassay for the detection of human interleukin-18/interferon-gamma-inducing factor using human myelomonocytic KG-1 cells.

Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a novel cytokine which plays an important role in Th1 responses. Here we describe a simple, sensitive bioassay for human IL-18 using the human myelomonocytic cell line, KG-1, which produces IFN-gamma in response to human IL-18. IFN-gamma production induced by human IL-18 was completely blocked by an antibody against human IL-18. Human IL-18 could be measured in a concentration range from approximately 100 to 10,000 pg/ml, and intra- and inter-assay coefficient variations were both below 15%. It was possible to measure human IL-18 in human serum, cell lysate or culture supernatant by this bioassay. Thus, the human IL-18 bioassay can be expected to be useful in the investigation of the relationship between human IL-18 and various diseases or in analyzing the mechanisms of human IL-18 secretion from IL-18 producing cells.

Animals↗

Conditioned eyeblink response is impaired in mutant mice lacking NMDA receptor subunit NR2A.

NMDA receptor channels, heteromeric assemblies of subunits with diverse subtypes, play critical roles in various kinds of synaptic plasticity underlying learning and memory. To elucidate the roles of subunits NR2A and NR2C in motor learning, we investigated acquisition of the classically conditioned eyeblink response in a delayed-conditioning paradigm by gene knockout mice. Mutant mice lacking NR2C exhibited no significant defect; however, early acquisition of the task was impaired in mutant mice lacking NR2A or both NR2A and NR2C. Based on the distribution of these subunits in brain, these results indicate that acquisition of the conditioned response does not depend on NMDA receptors in the cerebellar cortex, but that its early acquisition involves the hippocampus and/or cerebellar deep nuclei.

Animals↗

Proteolytic processing of presenilin-1 (PS-1) is not associated with Alzheimer's disease with or without PS-1 mutations.

Cerebral presenilin-1 protein (PS-1) is normally composed of the amino-terminal fragment (NTF) with Mr 28 kDa and the carboxy-terminal fragment (CTF) with 18 kDa. We analyzed human PS-1 in brains with early-onset familial Alzheimer's disease (FAD) with and without PS-1 mutations to study whether mutated PS-1 was abnormally metabolized. Cerebral PS-1 were found to be cleaved into two fragments of NTF and CTF independently of the occurrence of PS-1 mutation in human brains. A small portion of PS-1 was recently found to suffer another processing by caspase-3, an apoptosis-related cysteine protease. In contrast to the recent finding that the Volga-German mutation on presenilin-2 (PS-2) affects the increasing caspase-3 PS-2 fragment, the PS-1 mutation did not cause a significant change in PS-1 fragmentation. We conclude that PS-1 fragmentation and other (probably caspase-3-mediated) digestion following apoptosis occur independently of PS-1 mutations.

Alzheimer Disease↗

Exchangeability of the b subunit of the Cl(-)-translocating ATPase of Acetabularia acetabulum with the beta subunit of E. coli F1-ATPase: construction of the chimeric beta subunits and complementation studies.

The gene encoding the b subunit of the Cl(-)-translocating ATPase (aclB) was isolated from total RNA and poly(A)+ RNA of Acetabularia acetabulum and sequenced (total nucleotides of 3038 bp and an open reading frame with 478 amino acids). The deduced amino acid sequence showed high similarity to the beta subunit of the F type ATPases, but was different in the N-terminal 120 amino acids. The role of the N-terminal region was investigated using an F -ATPase beta-less mutant of E. coli, JP17. The JP17 strain expressing the aclB could not grow under conditions permitting oxidative phosphorylation, although ACLB was detected in the membrane fraction. The beta subunit was divided into three portions: amino acid position from 1 to 95 (portion A), 96 to 161 (portion B) and 162 to the C-terminus (portion C). The corresponding regions of ACLB were designated as portions A' (from 1 to 106), B' (from 107 to 172) and C' (from 173 to 478). Chimeric proteins with combinations of A-B'-C', A-B-C' and A'-B-C restored the function as the beta subunit in E. coli F0F1-complex, but those with combinations of A'-B'-C and A-B'-C had no function as the beta subunit. These findings suggested that portion B plays an important role in the assembly and function of the beta subunit in the F0F1-complex, while portion B' of ACLB exhibited inhibitory effects on assembly and function. In addition, portion A was also important for interaction of the beta subunit with the alpha subunit in E. coli F0F1-complex. These findings also suggested that the b subunit of the Cl(-)-translocating ATPase of A. acetabulum has a different function in the Cl(-)-translocating ATPase complex, although the primary structure resembled to the beta subunit of the F1-ATPase.

Acetabularia↗

Detection of interstellar ethylene oxide (c-C2H4O).

We report the identification of 10 transitions that support the detection of the small cyclic molecule ethylene oxide (c-C2H4O) in Sgr B2N. Although one of these transitions is severely blended, so that an accurate intensity and line width could not be determined, and two other lines are only marginally detected, we have done Gaussian fits to the remaining seven lines and have performed a rotation diagram analysis. Our results indicate a rotation temperature T(rot) = 18 K and a molecular column density N(c-C2H4O) = 3.3 x 10(14) cm-2, corresponding to a fractional abundance relative to molecular hydrogen of order 6 x 10(-11). This is a factor of more than 200 higher than the abundance for this molecule suggested by the "new standard" chemistry model of Lee, Bettens, & Herbst. This result suggests that grain chemistry might play an effective role in the production of c-C2H4O. No transitions of this molecule were detected in either Sgr B2M or Sgr B2NW.

Astronomical Phenomena↗

Odor exposure reveals non-uniform expression profiles of c-Jun protein in rat olfactory bulb neurons.

In the main olfactory bulb, neurons are arranged strategically in distinct layers among which translaminar synaptic transmission can be made from the superficial, sensory to the deep, output layers that account for the processing of olfactory information. To search for stimulus-transcription coupling thought to be operated differentially in several cell types, c-Jun expression was examined immunohistochemically in rat olfactory bulb following 30-min odor stimulation with acetic acid and 1-butanol. c-Jun was rapidly induced in neuronal cell nuclei belonging to periglomerular, tufted, mitral and granule cells. The disappearance of c-Jun, however, differed between each cell type. In the glomerular layer, the glomeruli composed of c-Jun-expressing periglomerular cells were seen. Different odors led to labeling of different sets of glomeruli. The labeled periglomerular cells disappeared within 2 h. In all the deeper layers, however, a rather homogeneous label was noted for the tufted, mitral and granule cells present throughout the olfactory bulb, regardless of the difference in odor. In tufted and mitral cells, the c-Jun expression persisted for 4 days after odor stimulation. In the granule cell layer, numerous granule cells increased c-Jun immunoreactivity which lasted for 1 day following odor application. In control rats which were given clean air, the basal amount of c-Jun expression was seen confined to scattered granule cells. The results suggest that c-Jun is expressed in a variety of odorant-stimulated bulb neurons with a time course being dependent on cell type.

1-Butanol↗