Biomedical subjects

T Kamada

Publications and source records attributed to T Kamada.

At least 37 records · Page 2Linked to original sources

PubMed2001

Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance.

The aim of this study was to clarify the immunological and virological responses to pre-administration of interferon-gamma prior to initiation of interferon-alpha treatment in patients with refractory chronic hepatitis C. Twenty-two nonresponders to 6-months of IFN-alpha treatment were enrolled. The hepatitis C virus (HCV) genotype was Ib in all. Natural IFN-gamma (1 MIU/day) was administered daily for 14 days followed by natural IFN-alpha (5 MIU/day) daily for 14 days and then three times weekly for 22 weeks. Serum immunological parameters (IL-10, neopterin, BMG, sCD8, sCD4, IL-6, IL-12) were measured as were the levels of several cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, IL-6, IL-10). Three patients dropped out; two because of the occurrence of other diseases and one because of an adverse effect. At the end of the period of IFN-alpha treatment, HCV-RNA had become negative in six of 19 patients (end-of treatment response; ETR). Six months after the completion of IFN administration, a virological sustained response (SR) was seen in two of 19 patients. The mean serum levels of IL-10 were significantly decreased 6 weeks after the start of treatment. Other immunological parameter levels increased significantly during the period of IFN-gamma administration, and tended to return to the pretreatment level after the start of IFN-alpha administration. Univariate logistic regression analysis showed that the initial change in the levels of these parameters or the change in the ratios of Th1/Th2 parameter levels are useful factors indicative of the end of the treatment response. These findings suggest that priming with IFN-gamma prior to the initiation of IFN-alpha treatment in patients with refractory chronic hepatitis C can modulate the host immune response and this might contribute to viral clearance.

Antiviral Agents↗

PubMed2001

Clinicopathological features of gastric mucosa-associated lymphoid tissue lymphoma: a comparison with diffuse large B-cell lymphoma without a mucosa-associated lymphoid tissue lymphoma component.

BACKGROUND AND AIMS: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma without a MALT lymphoma component (DLL). METHODS: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low-grade MALT lymphoma, 10 patients with high-grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age- and sex-matched control subjects. RESULTS: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low-grade MALT lymphomas and 1/9 for high-grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly (P < 0.05). Ninety-two percent of low-grade MALT lymphomas and 80% of high-grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low-grade MALT lymphoma than in age- and sex-matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls. CONCLUSIONS: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis.

Adult↗

PubMed2001

Duodenogastric reflux is associated with antral metaplastic gastritis.

BACKGROUND: It has long been suspected that duodenogastric reflux plays a role in the pathogenesis of intestinal metaplasia (IM), although recent studies have demonstrated a close association between Helicobacter pylori infection and gastroduodenal diseases, including IM. The objective of this study was to investigate the relation among IM and duodenogastric reflux, H pylori infection, and smoking. METHODS: Subjects with "marked" characteristics of IM, all with extensive prepyloric distribution at endoscopy that was confirmed histologically, were studied as an IM group (27 men, 26 women; mean age, 64 years). A control group was comprised by subjects without characteristics of IM (29 men, 28 women; mean age, 63 years). Fasting pH, total bile acid concentration, and ammonia concentration were measured in the gastric juice of all participants. Histologic examination endoscopic biopsy specimens were evaluated histologically. H pylori infection was determined by serum antibody and urease testing, and by histology. Serum gastrin and pepsinogen concentrations, and gastric emptying time were measured. Dietary, drinking, and smoking habits were recorded. Comparisons were made between groups and analyzed statistically. RESULTS: The pH and total bile acid concentrations were significantly higher in the IM group than the control group (p < 0.01). No significant difference in H pylori infection was found between the IM and control group. Smoking was associated with IM (odds ratio [OR], 15.74; 95% CI, 3.96 to 62.50). CONCLUSIONS: A high pH and total bile acid concentration and smoking were associated with "marked" IM, suggesting that these factors may play a role in the development of IM.

Duodenogastric Reflux↗

PubMed2001

Plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 are increased in the coronary circulation in patients with acute coronary syndrome.

BACKGROUND: Previous studies on atherectomy specimens from patients with acute coronary syndrome (ACS) implicated the role of proteolytic enzymes. We examined whether the plasma levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were increased in the coronary circulation in ACS. METHODS AND RESULTS: The plasma levels (nanograms per milliliter) of MMP-9 and TIMP-1 in the aorta (Ao) and great cardiac vein (GCV) were measured in 29 patients with ACS (20 with acute myocardial infarction [group 1] and 9 with unstable angina [group 2]), 17 with stable effort angina (group 3), and 20 control subjects (group 4). Group 1 patients had occlusion in the left anterior descending artery (LAD), and groups 2 and 3 patients had culprit lesion in the LAD. In group 1 blood samples were obtained at the time of direct coronary angioplasty done within 12 hours after the onset. The Ao level of either MMP-9 or TIMP-1 did not differ among the 4 groups. The GCV-Ao differences in MMP-9 and TIMP-1 were both significantly increased in groups 1 and 2 compared with those in group 4. Neither of them was different between groups 3 and 4. Neither the GCV-Ao difference in MMP-9 or TIMP-1 level was correlated with the maximal creatine kinase level in group 1. CONCLUSIONS: Increased plasma levels of MMP-9 and TIMP-1 were detected in the coronary circulation in ACS patients, suggesting a process of active plaque rupture in ACS.

Acute Disease↗

PubMed2001

Failure of exclusion of internal iliac artery aneurysms.

PURPOSE: We investigated in detail the state of internal iliac artery (IIA) aneurysms over the midterm after the exclusion procedure. METHODS: From January 1990 to December 1998, 29 patients underwent the exclusion procedure for IIA aneurysms. The medical records of 27 survivors were retrospectively reviewed, and 30 excluded aneurysms of these patients were followed up with computed tomography scanning over the midterm. RESULTS: In the immediate postoperative period, 26 aneurysms were completely thrombosed, and four were incompletely thrombosed. In the midterm, 24 aneurysms were completely thrombosed (complete group), and six were incompletely thrombosed (incomplete group). No aneurysms expanded or ruptured during the follow-up period from 6 to 98 months (mean, 26 months). The size of the excluded aneurysm decreased in 22 of 24 aneurysms in the complete group, but no change in size was noted in the six aneurysms in the incomplete group. The preoperative size of the IIA aneurysm in the incomplete group was significantly larger than that in the complete group (P =.0047). The size of two aneurysms in the incomplete group was smaller than 3.0 cm. The aneurysms in the incomplete group extended significantly deep into the pelvis as compared with those in the complete group (P =.0008). CONCLUSIONS: The exclusion of IIA aneurysm did not reliably result in thrombosis of the aneurysm. For IIA aneurysms extending deeply into the pelvis, even if the size of the aneurysm is smaller than 3.0 cm, the exclusion procedure should not be performed.

Aged↗

PubMed2001

The clp1 gene of the mushroom Coprinus cinereus is essential for A-regulated sexual development.

Sexual development in the mushroom Coprinus cinereus is under the control of the A and B mating-type loci, both of which must be different for a compatible, dikaryotic mycelium to form between two parents. The A genes, encoding proteins with homeodomain motifs, regulate conjugate division of the two nuclei from each mating partner and promote the formation of clamp connections. The latter are hyphal configurations required for the maintenance of the nuclear status in the dikaryotic phase of basidiomycetes. The B genes encode pheromones and pheromone receptors. They regulate the cellular fusions that complete clamp connections during growth, as well as the nuclear migration required for dikaryosis. The AmutBmut strain (326) of C. cinereus, in which both A- and B-regulated pathways are constitutively activated by mutations, produces, without mating, dikaryon-like, fertile hyphae with clamp connections. In this study we isolated and characterized clampless1-1 (clp1-1), a mutation that blocks clamp formation, an essential step in A-regulated sexual development, in the AmutBmut background. A genomic DNA fragment that rescues the clp1-1 mutation was identified by transformations. Sequencing of the genomic DNA, together with RACE experiments, identified an ORF interrupted by one intron, encoding a novel protein of 365 amino acids. The clp1-1 mutant allele carries a deletion of four nucleotides, which is predicted to cause elimination of codon 128 and frameshifts thereafter. The clp1 transcript was normally detected only in the presence of the A protein heterodimer formed when homokaryons with compatible A genes were mated. Forced expression of clp1 by promoter replacements induced clamp development without the need for a compatible A gene combination. These results indicate that expression of clp1 is necessary and sufficient for induction of the A-regulated pathway that leads to clamp development.

Amino Acid Sequence↗

PubMed2001

Antigen presentation by murine peritoneal cavity macrophage-derived dendritic cells.

Murine peritoneal cavity macrophage derived dendritic cells (PEC-DC) generated using early growth factors, interleukin 4 and granulocyte-macrophage colony-stimulating factor followed by maturation in interferon-gamma plus either, Toxoplasma lysate antigen (TLA) or lipopolysaccharide, bind TLA by a nonspecific mechanism and continue to express major histocompatibility complex class II antigens after 24 h of culture in vitro. Moreover, the proliferation of CD3+ spleen T cells from mice immunized with Toxoplasma gondii homogenate, induced by PEC-DC-mediated antigen presentation was statistically significant and of consistent amplitude. This accessory function of PEC-DC is antigen specific.

Animals↗

PubMed2001

Mitochondrial coupling factor 6 as a potent endogenous vasoconstrictor.

We demonstrated recently that coupling factor 6, an essential component of the energy-transducing stalk of mitochondrial ATP synthase, suppresses the synthesis of prostacyclin in vascular endothelial cells. Here, we tested the hypothesis that coupling factor 6 is present on the cell surface and is involved in the regulation of systemic circulation. This peptide is present on the surface of CRL-2222 vascular endothelial cells and is released by these cells into the medium. In vivo, the peptide circulates in the vascular system of the rat, and its gene expression and plasma concentration are higher in spontaneously hypertensive rats (SHRs) than in normotensive controls. Elevation of blood pressure with norepinephrine did not affect the plasma concentration of coupling factor 6. Intravenous injection of recombinant peptide increased blood pressure, apparently by suppressing prostacyclin synthesis, whereas a specific Ab to coupling factor 6 decreased systemic blood pressure concomitantly with an increase in plasma prostacyclin. Interestingly, the antibody's hypotensive effect could be abolished by treating with the cyclooxygenase inhibitor indomethacin. These findings indicate that mitochondrial coupling factor 6 functions as a potent endogenous vasoconstrictor in the fashion of a circulating hormone and may suggest a new mechanism for hypertension.

Amino Acid Sequence↗

PubMed2001

Comparison of the accessory activity of murine peritoneal cavity macrophage derived dendritic cells and peritoneal cavity macrophages in a mixed lymphocyte reaction.

A detailed comparison of the accessory cell activities was carried out among murine peritoneal cavity macrophages (PEC-Mphi), peritonea] cavity macrophages stimulated with granulocyte-macrophage colony stimulating factor (GM-CSF) plus interleukin 4 (IL-4), the most popular cytokine combination widely used to generate dendritic cells (DC) and peritoneal cavity macrophage-derived DC (PEC-DC) using a two-way mixed lymphocyte reaction (MLR). All the cell types used efficiently induced statistically significant naïve T cell proliferation at all culture time points and responder:stimulator ratios used. However, marked differences were noted in the magnitude of the proliferative responses. These variations may be attributed to the intensity of expression of MHC class II glycoproteins, as well as the actual numbers of MHC class II+ cells.

Animals↗

PubMed2001

Detection of Cryptosporidium parvum oocysts in environmental water in Hokkaido, Japan.

Control of cryptosporidiosis is important in public health. Rivers that are polluted with Cryptosporidium and drinking water that is treated for drinking water production from polluted rivers could result in the waterborne disease of cryptosporidiosis. We carried out an epidemiological study of natural water supplies in Hokkaido, one of the largest dairy prefectures in Japan. To detect Cryptosporidium oocysts in environmental water, the filtration method was used for 28 samples, which were collected from 10 rivers. A method adapted from the United States Environmental Protection Agency (U.S. EPA) filtration method using a cartridge filter has been used for the collection of samples. Oocysts were separated from a pellet by discontinuous sucrose gradient method. Twelve samples were collected from 10 rivers and parasites were purified by iron (III) flocculation method. Cryptosporidium parvum oocysts were identified with the immunofluorescence antibody technique using DIF kit (Cellabs Pty. Ltd., Sydney/Australia). We detected Cryptosporidium oocysts in 6 out of 10 rivers sampled. Fifty percentage (14/28) of the samples were Cryptosporidium-positive. The average number of Cryptosporidium oocysts was 16.73/100 L (max. 80/100 L).

Animals↗

PubMed2001

Ontogeny of pig discrete Peyer's patches: expression of surface antigens.

Leukocyte populations present in the discrete Peyer's patches (PP) of the pig were characterized from birth (Day 0) to day 35 after birth by immunohistochemistry and image analysis. Immediately after birth, cell membrane expression of CD2 and CD3, major histocompatibilty complex (MHC) class 11 (both SLA (swine leukocyte antigen) -DQ+ and SLA-DR+), CD21, 74-22-15 and surface immunoglobulin (sIg) were all demonstrable. Computer assisted morphometric techniques were used to confirm the significant expansion of these cell populations from birth onwards. The distribution of the cell types was not random but suggested a preferential retention of cells at specific sites. This implies a degree of organization of immunological cells within the discrete PP, enhancing the potential to mount immune responses in the most efficient manner.

Animals↗

PubMed2001

[Prognostic significance of myocardial imaging with iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid in patients with angina pectoris].

OBJECTIVES: To assess the clinical significance of iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid(BMIPP) single photon emission computed tomography(SPECT), the predictive value of BMIPP imaging in patients with angina pectoris was evaluated. METHODS: One hundred seventy-four patients who underwent BMIPP imaging in our institution were aged 61.8 +/- 11 years. One hundred thirty-five patients had stable angina and 39 had unstable angina at the time of examination. Patients with previous myocardial infarction or myocardial disorders were excluded. Early and delayed images were acquired in BMIPP SPECT, and the images were analyzed visually. Cardiac events were classified into hard and soft events: the former consisted of cardiac death and nonfatal myocardial infarction, and the latter included coronary revascularization and heart failure. RESULTS: The findings of BMIPP imaging were normal in 82 patients and abnormal in 92. During follow-up of 15.5 +/- 9.5 months, hard events were observed in 4 patients and soft events in 53. In patients with normal BMIPP imaging, soft events were observed in nine patients, but no hard event was encountered. Furthermore, in patients with both normal BMIPP and stress thallium imagings, no cardiac event was observed during 2 years. In contrast, 4 hard events and 44 soft events occurred in patients with abnormal BMIPP imaging. Patients with abnormal BMIPP imaging had a higher incidence of soft events than those with normal BMIPP imaging, regardless of the type of angina(16/62 vs 3/73, p < 0.0005 for stable angina; 28/30 vs 6/9, p < 0.0001 for unstable angina). CONCLUSIONS: The finding of BMIPP imaging correlates well with the mid-term prognosis of patients with angina pectoris. Since BMIPP SPECT is performed without stress to the patient, this imaging modality is important in evaluating patients with stable or unstable angina.

Angina Pectoris↗

PubMed2000

Enhanced phospholipase C activity in the cultured skin fibroblast obtained from patients with coronary spastic angina: possible role for enhanced vasoconstrictor response.

OBJECTIVES: We measured phospholipase C (PLC) activity in the cultured skin fibroblasts obtained from patients with and without coronary spasm and examined its correlation with coronary artery vasomotility. BACKGROUND: Coronary artery vasomotility is enhanced in coronary spastic angina (CSA), but no information is available for the intracellular signaling. In spontaneously hypertensive rats, PLC activity in the skin fibroblasts has been shown to be enhanced. METHODS: Skin fibroblasts obtained from 24 patients with CSA-14 with organic coronary artery disease (CAD) and 12 control subjects--were cultured by the explant method. Activity of PLC was determined by incubating the membrane fraction with 3H-phosphatidyl inositol bisphosphate and by quantifying 3H-inositol trisphosphate. In patients with CSA and control subjects, the relations between PLC activity and coronary artery basal tone and constrictor response to intracoronary acetylcholine (ACh) were examined. RESULTS: Activity of PLC (pmol/protein [mg] per min) was 1.74+/-0.19 in patients with CSA; 0.90+/-0.12 in patients with CAD; and 0.65+/-0.07 in control subjects (p<0.001, patients with CSA vs. patients with CAD and control subjects; p = NS, patients with CAD vs. control subjects). According to the Lineweaver-Burk plot, Michaelis constant (micromol/liter) of PLC was 28+/-4 in patients with CSA; 49+/-14 in patients with CAD; and 56+/-10 in control subjects (p<0.05, patients with CSA vs. control subjects), whereas the maximal velocity was not different between the three groups. There were significant positive correlations between PLC activity and both basal tone (p = 0.0108) and response to ACh (p = 0.0053). Western blot analysis using membrane fraction demonstrated that 89% of PLC isoenzymes detected was of the delta1 isoform. CONCLUSIONS: Because the PLC activity measured was genetically defined and was positively correlated with coronary artery vasomotility, enhanced PLC activity may be involved in the pathogenesis of coronary spasm.

Angina Pectoris, Variant↗

PubMed2000

Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C: a retrospective cohort study of 738 patients.

The effect of interferon on the long-term clinical outcome of patients with chronic hepatitis C remains unclear. This study included 594 patients with chronic hepatitis C who received interferon-alpha therapy (Interferon group) and 144 patients with chronic hepatitis C who did not receive interferon (Control group). The patients in the Interferon group were classified into the following three groups based on the response of the serum aminotransaminase level of the patient during and after completion of the therapy protocol: sustained responders (n = 175), transient responders (n = 165), and non-responders (n = 254). The age, sex, serum aminotransaminase level, platelet count, histological staging, hepatitis C virus (HCV) subtype, and HCV concentration at baseline were adjusted with the Cox proportional hazards model. The length of follow-up for assessment of the risk for developing hepatocellular carcinoma (HCC) was 57.2 +/- 13.9 months in the Interferon group and 67.7 +/- 28.7 months in the Control group. Multivariate analysis showed that interferon therapy decreased the risk for developing HCC by 48% compared with that in the Control group (P = 0.064). The older the age, being male, having a low platelet count, and higher histological stage were independent factors associated with the development of HCC. The hazard rate ratio for development of HCC in the sustained responders, transient responders, and non-responders was 0.16 (95% confidence interval [CI]: 0.04-0.62), 0.27 (95% CI: 0. 09-0.79), and 0.74 (95% CI: 0.37-1.48), respectively. During follow-up, 18 patients in the Interferon group died (10 from liver-related diseases) and 17 patients in the Control group died (10 from liver-related diseases). No sustained responder or transient responder in the Interferon group died of liver-related disease. The cumulative survival rates of the Interferon and Control groups were nearly identical during the first 5 years following diagnosis. Thereafter, the cumulative survival rate of the Control group declined, resulting in an 8-year survival rate in the Interferon and Control groups of 97% and 81%, respectively (P = 0. 061). Similar trends were seen in the survival analysis of those who had died of liver disease: the 8-year survival rates of the Interferon and Control groups were 98% and 88%, respectively (P = 0. 32). Our study demonstrated that interferon therapy significantly lowered the incidence of HCC among patients with chronic hepatitis C who showed sustained normalization and among patients who showed transient normalization of the serum aminotransferase level after completion of interferon therapy. The survival analyses and determination of cause of death suggested that interferon therapy improves the long-term survival of chronic hepatitis C patients who respond to this therapy, possibly by decreasing mortality from liver-related diseases.

Antiviral Agents↗

PubMed2000

Time to recover from atrial hormonal, mechanical, and electrical dysfunction after successful electrical cardioversion of persistent atrial fibrillation.

Although transient atrial dysfunction has been reported after electrical cardioversion of atrial fibrillation (AF), the difference in the time to recover from the atrial hormonal, mechanical, and electrical dysfunction has not been described. Thus, we evaluated the time course of recovery from atrial hormonal, mechanical, and electrical dysfunction after cardioversion in patients with nonvalvular AF. We attempted electrical cardioversion in 87 consecutive patients with nonvalvular AF that had persisted for > or =6 months, and in 24 patients (28%) with maintained sinus rhythm for > or =6 months. To evaluate atrial hormonal, mechanical, and electrical dysfunction in these 24 patients, we measured plasma concentration of atrial natriuretic peptide, the atrial peak velocity in transmitral flow, and the ratio of peak systolic-to-diastolic pulmonary venous flow (S/D ratio) using echocardiography, and the duration and the root mean voltage for the terminal 20 ms (LP20) of the filtered P wave using P-wave signal-averaged electrocardiography. Atrial natriuretic peptide rapidly returned to baseline within 1 day after cardioversion, and maintained these levels for 6 months. Atrial peak velocity in transmitral flow and S/D ratio were significantly increased at 2 weeks, and continued to increase until 1 month, and then reached a plateau. The duration and LP20 began to recover only 6 months after cardioversion. One to 3 years after conversion, the duration and LP20 had nearly reached a plateau, but the latter value remained below normal. In patients with nonvalvular AF of prolonged duration, recovery from atrial electrical dysfunction after sinus conversion took much longer than that from either atrial hormonal or mechanical dysfunction.

Aged↗

PubMed2000

Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension : modulation of nitric oxide synthesis by salt intake.

BACKGROUND: High salt intake suppresses the effect of nitric oxide (NO) in the peripheral resistance vessels in animal models. We tested the hypothesis that the modulation of endogenous NO is related to salt sensitivity in human hypertension. METHODS AND RESULTS: Inpatients with essential hypertension (n=24) were maintained on a normal-salt diet (12 g/d NaCl) for 3 days, a low-salt diet (2 g), a high-salt diet (20 to 23 g), and a low-salt diet for 7 days. Normotensive subjects (n=16) were maintained on the first 2 salt diets. The hypertensive patients whose average 24-hour blood pressure was increased by >5% by salt loading were assigned to group 1 (n=8) and the others to group 2 (n=16). Nitrate plus nitrite (NO(x)) was measured by the Griess method, and asymmetrical dimethylarginine (ADMA) by high-performance liquid chromatography. The plasma NO(x) level during the normal-salt diet was lower in group 1 than in group 2 and the normotensive group. After salt loading, the plasma NO(x) level was decreased and reversed after the second salt restriction. Plasma ADMA level was increased after salt loading and decreased after salt restriction. The change in plasma NO(x) level was correlated inversely with those in blood pressure (r=-0.59, P=0.0007) and plasma ADMA level (r=-0.64, P=0.003) after salt loading and restriction. CONCLUSIONS: Modulation of NO synthesis by salt intake may be involved in a mechanism for salt sensitivity in human hypertension, presumably via the change in ADMA.

Adult↗

PubMed2000

A mutation in the eln2 gene encoding a cytochrome P450 of Coprinus cinereus affects mushroom morphogenesis.

A dominant mutation of the elongationless2 (eln2) gene of the mushroom Coprinus cinereus (eln2-1) affects pattern formation in the development of fruit body primordia, causing dumpy primordia which culminate in mature fruit bodies with short stipes. Phenotypic analyses revealed disturbance of tissue organization and cell morphogenesis in the primordial shaft and suggested that the defects in the primordial shaft interfere with differentiation of the stipe tissue in the mutant primordia. The eln2 locus was assigned to chromosome XII and the eln2-1 mutant gene was cloned from a chromosome XII-specific cosmid library as a genomic fragment that brings about the dominant mutant phenotype. The eln2 gene encodes a novel type of microsomal cytochrome P450 enzyme (CYP502) and is constitutively expressed. The eln2-1 mutation is a 4-bp deletion in the 3'-terminal region of the gene, leading to truncation of C-terminal 18 amino acids. We suggest that the truncation affects the activity of the CYP502 enzyme.

Amino Acid Sequence↗

PubMed2000

Eicosapentaenoic acid reduces pulmonary edema in endotoxemic rats.

BACKGROUND: Recently, eicosapentaenoic acid (EPA) was found to have an anti-inflammatory effect attributable to diminished synthesis of arachidonic acid metabolites that initiate acute lung injury. We evaluated the ability of dietary EPA supplementation to prevent endotoxin-induced acute lung injury in rats. MATERIALS AND METHODS: Rats fed a standard diet were divided randomly into two groups: for 2 weeks one group additionally was fed 1000 mg/kg/day of EPA ethyl ester emulsion (EPA rats), while in the other group the diet was supplemented with vehicle alone (control rats). Fatty acid components of alveolar macrophages (AM) were measured, as well as leukotriene (LT) B(4) and LTB(5) production by AM exposed in vitro to calcium ionophore A23187. Plasma concentrations of thromboxane (Tx) B(2), a stable metabolite of TxA(2), were examined 1 h after inducing lung injury with endotoxin (2 mg/kg iv). At 6 h, wet/dry (W/D) weight ratios were calculated for the lungs to assess pulmonary edema, and neutrophils were counted in pulmonary parenchyma and peripheral blood. RESULTS: Arachidonic acid content and LTB(4) generation in AM were significantly lower in EPA rats than in controls; conversely, EPA content and LTB(5) generation in AM were significantly higher in the EPA group. Neutrophil counts in lung parenchyma and peripheral blood did not differ between groups, but W/D and plasma TxB(2) concentrations were significantly lower in EPA rats. CONCLUSIONS: EPA supplementation depressed arachidonic acid content and LTB(4) generation in AM and plasma TxB(2) in our model, leading to decreased pulmonary edema.

Animals↗