Biomedical subjects

M Sakai

Publications and source records attributed to M Sakai.

At least 109 records · Page 6Linked to original sources

PubMed2000

A 38 kb segment containing the cdc2 gene from the left arm of fission yeast chromosome II: sequence analysis and characterization of the genomic DNA and cDNAs encoded on the segment.

A genomic 38 kbp segment on the c1750 cosmid clone containing the cdc2 gene, located in the left arm of chromosome II from Schizosaccharomyces pombe, was sequenced. The segment was found to have five previously known genes, pht1, cdc2, his3, act1 and mei4. Among 11 coding sequences (CDSs) predicted by the gene finding software INTRON.PLOT., four CDSs, pi007, pi010, pi014 and pi016, had considerable similarity to 40S ribosomal protein, glycosyltransferase, cdc2-related protein kinase and alpha-1, 2-mannosyltransferase, respectively. Another unusually huge open reading frame (ORF) (pi011), consisting of 2233 amino acids, existed, having significant homology to alpha-amylase, granule-bound glycogen synthase and the Sz. pombe YS 1110 clone product at the N-terminal, middle and C-terminal regions, respectively. All the predicted 11 CDSs were experimentally analysed by RACE PCR. The sequencing of the RACE products revealed that there were two small overlaps at the 3' untranslated regions (UTRs) between pi004 and pi005 (17 bp) and between pi007 and pi008 (2 bp). The distances between 5' end of the 5'UTR and the putative translation initiation codon varied from 10 to 302 nucleotides (nt) among the nine CDSs successfully analysed by 5'-RACE. The expression level of each CDS on this clone was determined. Among the 16 genes on this clone, the previously determined genes, pht1, cdc2, his3 and act1, were found to be most highly expressed. Finally, cDNAs of all the newly identified genes were detected by RACE, proving the actual expression of these genes. The nucleotide sequence has been submitted to the EMBL database under Accession No. AB004534.

Base Sequence↗

PubMed2000

Expression of HLA-DR and its enhancing molecules in muscle fibers in polymyositis.

Polymyositis (PM) is an autoimmune inflammatory muscle disease of unknown cause in which cellular immunity is thought to play an important pathogenic role. Class II major histocompatibility complex (class II MHC: human leukocyte antigen (HLA)-DR operates as a cofactor of antigen presentation in immunological responses. There has been a major debate over whether muscle fibers themselves synthesize and express HLA-DR molecules and play a role in antigen presentation in PM pathogenesis. In this study, we demonstrated that most muscle fibers from patients with PM synthesized and expressed HLA-DR molecules on their surface. Human leukocyte antigen-DR expression was highly specific to PM. In addition, class II transactivator (CIITA), human leukocyte antigen DM (HLA-DM), and invariant chain (Ii), which are indispensable for expression of mature HLA-DR molecules and for antigen processing and presentation, were co-expressed. One of the cytokines that could induce this expression is interferon-gamma (IFN-gamma), released by activated lymphocytes. Our results indicate that in PM muscle fibers synthesize and express HLA-DR molecules and may contribute to the inflammatory responses together with lymphocytes.

Adult↗

PubMed2000

Intrafamilial phenotypic variation in limb-girdle muscular dystrophy type 2C with compound heterozygous mutations.

Two Japanese-Brazilian siblings with type 2C limb girdle muscular dystrophy showed a maternal 521-T deletion in exon 6 and a larger paternal deletion of exon 6 in the gamma-sarcoglycan gene. One sib was ambulant at 29 years of age, whereas the other sib was confined to a wheelchair at the age of 12. Sarcoglycan staining of the muscle was reduced in both siblings but it did not correlate with the observed variability of the clinical severity.

Adult↗

PubMed2000

In vitro modulation of fish phagocytic cells by beta-endorphin.

The activation of rainbow trout, Oncorhynchus mykiss, and carp, Cyprinus carpio, phagocytic cells by synthetic chum salmon, O. keta, beta-endorphin was analysed in vitro. Rainbow trout head kidney leukocytes were cultured in RPMI 1640 medium containing 1, 10, 50 or 100 ng ml-1 of chum salmon beta-endorphin and the production of superoxide anion was measured via the reduction of nitroblue tetrazolium (NBT) in vitro. Macrophages incubated with 10 ng ml-1 up to 100 ng ml-1 of beta-endorphin showed an increase in their production of superoxide anion in comparison with control macrophages which were cultured without hormone. beta-endorphin also increased the production of superoxide anion in phagocytic cells prepared from kidney of carp. This stimulation was inhibited by naloxone. Phagocytic cells treated with beta-endorphin also displayed increased phagocytic activity and phagocytic index. These results showed that beta-endorphin in lower vertebrates activates the function of phagocytic cells in vitro.

Amino Acid Sequence↗

PubMed2000

Identification of carp proopiomelanocortin-related peptides and their effects on phagocytes.

We report the immunomodulating effects of proopiomelanocortin (POMC)-related peptides on phagocytic cells in carp. The complete amino acid sequences of two carp POMCs (I and II) were deduced from the nucleotide sequences after cDNA cloning. Both POMCs consist of 194 amino acids (91% sequence identity) including identical alpha-melanotropin (MSH) and beta-endorphin (EP). All hormonal peptides derived from two POMCs were identified by mass spectrometry after separation by high-performance liquid chromatography of an acid-acetone extract from a single pituitary. These peptides were alpha-MSH, N-Des-Ac-alpha-MSH, di-Ac-alpha-MSH, beta-MSH I, beta-MSH-II, N-Ac-beta-EP(1-29), corticotropin-like intermediate lobe peptide I and II and N-terminal peptide of POMC I and II. The immunomodulating effects of synthetic MSHs and EPs on phagocytic cells from carp head kidney were examined. Di-Ac-alpha-MSH, beta-MSH I, N-Ac-beta-EP(1-29) and beta-EP(1-29) increased the production of superoxide anion at 0.1-100 ng ml-1 for these MSHs and 1-100 ng ml-1 for EPs in RPMI 1640 medium.

Amino Acid Sequence↗

PubMed2000

Clinical experience of Argatroban for anticoagulation in cardiovascular surgery.

PURPOSE: We have reviewed our experience with Argatroban-a direct thrombin inhibitor for anticoagulation--in a variety of cardiovascular operations, and in extracorporeal circulation, as a substitute for heparin. SUBJECTS AND METHODS: 60 patients receiving anticoagulation with Argatroban were classified into the following four groups. Group 1; 20 patients with anticoagulation therapy after cardiac surgery. Group 2; 8 patients with extracorporeal circulation for continuous hemofiltration for either pre- or post-operative control of acute renal failure. Argatroban was used alone or in combination with nafamostat mesilate. Group 3, one patient with replacement of the descending aorta with left heart assist and 15 patients with percutaneous cardiopulmonary support. And Group 4, 16 patients undergoing vascular surgery including the abdominal aorta. The target activated clotting time was individually set for each group. In Group 1, the coagulofibrinolytic activity and platelet function were measured precisely. Bleeding and complications were examined in all groups. RESULTS: Group 1; the targeted activated clotting time of 150-180 seconds was achieved by a dosage of 0.4-0.8 microgram/kg/min Argatroban. Group 2; the activated clotting time of 150-180 seconds was achieved by 0.05-1.6 micrograms/kg/min (concomitance), or by 0.02-2.5 micrograms/kg/min (alone). Group 3; the activated clotting time of 180-200 seconds by 0.05-3.86 micrograms/kg/min. And Group 4; the activated clotting time of around 150 seconds by 2.0 micrograms/kg/min with initial bolus infusion of 0.1 mg/kg. Argatroban did not promote post-surgery bleeding and had no unfavorable effect on coagulo-fibrinolysis or on platelet activity. CONCLUSION: Argatroban may be useful as an anticoagulant in the field of cardiovascular surgery as a substitute for heparin, without causing any post-surgery bleeding complication, or influencing the fibrinolytic activities or platelet functions.

Aged↗

PubMed2000

Group-II phospholipase A(2) enhances oxidized low density lipoprotein-induced macrophage growth through enhancement of GM-CSF release.

Inflammatory process plays an important role in the development and progression of atherosclerotic lesions. Recently, group-II phospholipase A(2) (PLA(2)), an inflammatory mediator, was reported to exist in human atherosclerotic lesions and to enhance the development of murine atherosclerotic lesions. Oxidized low density lipoprotein (Ox-LDL) stimulates the growth of several types of macrophages in vitro. Since proliferation of macrophages occurs in atherosclerotic lesions, it is possible to assume that the Ox-LDL-induced macrophage proliferation might be involved in the progression of atherosclerosis. In this study, the role of group-II PLA(2) in the Ox-LDL-induced macrophage growth was investigated using thioglycollate-elicited mouse peritoneal macrophages. Thioglycollate-elicited macrophages significantly expressed group-II PLA(2) and released it into the culture medium. The Ox-LDL-induced thymidine incorporation into thioglycollate-elicited macrophages was three times higher than that into resident macrophages, whereas under the same conditions, granulocyte/macrophage colony-stimulating factor (GM-CSF) equally induced thymidine incorporation into both types of macrophages. Moreover, the Ox-LDL-induced GM-CSF release from thioglycollate-elicited macrophages was significantly higher than that from resident macrophages. In addition, the Ox-LDL-induced thymidine incorporation into macrophages obtained from human group-II PLA(2) transgenic mice and the GM-CSF release from these cells were significantly higher than those from their negative littermates, and the Ox-LDL-induced thymidine incorporation into human group-II PLA(2) transgenic macrophages was significantly inhibited by a polyclonal anti-human group-II PLA(2) antibody. These results suggest that the expression of group-II PLA(2) in thioglycollate-elicited macrophages may play an enhancing role in the Ox-LDL-induced macrophage growth through the enhancement of the GM-CSF release.

Animals↗

PubMed2000

Effects of probucol on cholesterol metabolism in mouse peritoneal macrophages: inhibition of HDL-mediated cholesterol efflux.

Macrophage-derived foam cells are known to play an essential role in the development and progression of atherosclerotic lesions. Probucol prevents oxidative modification of low-density lipoprotein (LDL) and lowers plasma contents of LDL and high-density lipoprotein (HDL). A recent report using apoE -/- mice demonstrated that probucol treatment enhanced atherosclerosis in apoE -/- mice more rapidly than that in untreated apoE -/- mice, and a reduction in plasma cholesterol by probucol was not the cause of enhancement of atherosclerotic lesions in probucol-treated apoE -/- mice. Moreover, probucol was reported to inhibit apoA-I mediated cholesterol efflux from mouse macrophages. These reports suggested that probucol might directly affect cholesterol metabolism in mouse macrophages. Thus, we investigated the effects of probucol on cholesterol metabolism in mouse resident peritoneal macrophages. Probucol did not affect degradation of acetylated LDL (Ac-LDL), degradation of LDL and endogenous cholesterol synthesis in mouse macrophages. However, it significantly inhibited HDL-mediated cholesterol efflux. Moreover, probucol partially (30%) inhibited the binding of HDL to mouse macrophages, and significantly activated acyl-coenzyme A:cholesterol acyltransferase (ACAT). Our results suggested that probucol inhibited HDL-mediated cholesterol efflux by inhibiting the binding of HDL to mouse macrophages and reducing HDL-accessible free cholesterol content by ACAT activation, thereby worsening atherosclerotic lesions in apoE -/- mice. However, it remains unclear whether probucol inhibits HDL-mediated cholesterol efflux from human macrophages.

Animals↗

PubMed2000

Brain control of mating behavior in the male cricket Gryllus bimaculatus DeGeer: the center for inhibition of copulation actions.

We re-examined the functional role of the brain and suboesophageal ganglion (SOG) in inhibiting mating behavior in the male cricket Gryllus bimaculatus DeGeer. Experiments were conducted by using mimetic stimulation to elicit copulation actions. To induce a change in the male internal state from a sexually responsive state to a sexually unresponsive state in the mating stage, noxious stimulation, head injury and leg pinching were used. Males that sustained a head injury became sexually unresponsive but became responsive as soon as the brain was removed, while males that underwent the same treatment remained unresponsive after the SOG was destroyed by sectioning. The inhibitory effects of the brain were also demonstrated by the fact that further removal of the SOG in the decerebrated males did not change their copulatory responsiveness, while removal of the brain in SOG-sectioned males markedly increased copulatory responsiveness. Furthermore, decerebrated males did not become sexually unresponsive by leg pinching, while SOG-sectioned males that had recovered sexual responsivenss, did. These results suggest that the brain, and not the SOG, plays a key role in the inhibition of copulation in the male cricket during the mating stage.

Journal Article↗

PubMed2000

Brain control of mating behavior in the male cricket Gryllus bimaculatus DeGeer: brain neurons responsible for inhibition of copulation actions.

We localized brain neurons responsible for the inhibition of copulation actions in the male cricket, Gryllus bimaculatus. Males with one connective-cut between the brain and the terminal abdominal ganglion (TAG) were able to perform normal reproductive behaviors such as courtship, copulation and spermatophore protrusion. However, copulation response tests using a female dummy showed that they failed to exhibit a transient inhibitory state after application of noxious stimulation in the mating stage and to exhibit a tonic inhibitory state in the post-copulatory sexual refractory stage. A partial cut of a single connective (hemilateral connective-cut) combined with the copulation response test and an axonal backfilling demonstrated that approximately 40 brain neurons (per one connective), whose somata were located in the posterior region of the protocerebrum and mainly contralaterally to their descending axons running through the dorso-medial part of the connective, were candidates for the inhibition of copulation actions, at least in the mating stage. In addition, we report here for the first time, that copulation actions can be elicited shortly after copulation even in intact males. This unusual behavior was frequently observed in fledglings after the final molt. The results are discussed from the perspective of the operation of the brain inhibition system on the central pattern generator (CPG) for copulation.

Journal Article↗

PubMed2000

Cost-effectiveness of intensive insulin therapy for type 2 diabetes: a 10-year follow-up of the Kumamoto study.

To evaluate the cost and effectiveness of intensive insulin therapy for type 2 diabetes on the prevention of diabetes complications in Japan, we performed economic evaluation based on a randomized controlled trial. A total of 110 patients with type 2 diabetes were randomly assigned into two groups, a multiple insulin injection therapy (MIT) group or a conventional insulin injection therapy (CIT) group, and were followed-up for 10 years. Economic evaluation (cost-consequences analysis) was applied to evaluate both health and economic outcomes. As outcome measures for effectiveness of intensive insulin therapy, the frequency of complications, such as retinopathy, nephropathy, neuropathy, macrovascular event, and diabetes-related death, was used. For estimating costs, a viewpoint of the payer (the National Health Insurance) was adopted. Direct medical costs associated with diabetes care during 10 years were calculated and evaluated. In a base case analysis, all costs were discounted to the present value at an annual rate of 3%. Sensitivity analyses were carried out to assess the robustness of the results to changes in the values of important variables. MIT reduced the relative risk in the progression of retinopathy by 67%, photocoagulation by 77%, progression of nephropathy by 66%, albuminuria by 100% and clinical neuropathy by 64%, relative to CIT. Moreover, MIT prolonged the period in which patients were free of complications, including 2.0 years for progression of retinopathy (P<0.0001), 0.3 years for photocoagulation (P<0.05), 1.5 years for progression of nephropathy (P<0.01) and 2.2 years for clinical neuropathy (P<0.0001). The total cost (discounted at 3%) per patient during the 10-year period for each group was $30310 and 31525, respectively. The reduction of total costs in MIT over CIT was mainly due to reduced costs for management of diabetic complications. Our results show that MIT is more beneficial than CIT in both cost and effectiveness. Therefore, MIT is recommended for the treatment of type 2 diabetic patients who require insulin therapy as early as possible from the perspective of both patients and health policy.

Adult↗

PubMed2000

Dorsal induction from dorsal vegetal cells in Xenopus occurs after mid-blastula transition.

We performed some experiments to investigate the temporal and spatial details of the dorsal induction exerted by dorsal vegetal cells in Xenopus embryo. Two dorsal vegetal cells (D1 cells) were transplanted into the ventral vegetal region of a recipient at the 32-cell stage. At various times after transplantation, the ventral animal-equatorial part was explanted and cultured. The explants isolated 5.5 h after transplantation (time 5.5) elongated and formed somites. In RT-PCR analysis, the expression of dorsal gene, chordin was activated in the explants isolated after time 4.0 (about the 4000-cell stage which corresponds to the mid blastula transition (MBT)) at control stage 10. In another series of experiments, ventral animal-equatorial and dorsal vegetal parts were isolated from the 4000-cell stage embryos and they were combined for 2.0-2.5 h. These ventral animal-equatorial explants elongated and formed somites. The chordin expression was also observed in the explants. But the 32- and 256-cell stage dorsal vegetal cells failed to exert the dorsalizing activity within the 2.0-2.5 h of the conjugation. These results suggest that 2 h contact after MBT is necessary and sufficient for the dorsal induction from the dorsal vegetal cells and it occurs as a result of the zygotic gene expression. Consistent with this idea, the zygotic dorsal genes, siamois and chordin were expressed on the upper regions of the transplanted D1 descendants at stage 10. Furthermore, this region began to gastrulate when the D1 cell was transplanted with upside-down orientation. Our data indicate that the upper region of the D1 descendants by itself act as the Spemann organizer rather than the Nieuwkoop center.

Animals↗

PubMed2000

Age-related modifications of effects of ketamine and propofol on rat hippocampal acetylcholine release studied by in vivo brain microdialysis.

BACKGROUND: We sometimes encounter impairment of learning and memory after general anesthesia in elderly patients. The aim of this study was to examine age-related modifications of the effects of ketamine and propofol on rat hippocampal acetylcholine (ACh) release because hippocampal cholinergic neurons are supposed to be involved in learning and memory. METHODS: The experiments were performed on male Wistar young rats (2 months old) and old rats (18 months old), using in vivo brain microdialysis technique under freely moving condition. After initial sampling of three collections, test drugs were administered. The ACh release was determined by the HPLC-ECD method. RESULTS: In old rats, the hippocampal basal ACh release was significantly lower than in young rats. Ketamine (25 and 50 mg kg(-1) i.p.) increased and propofol (25 and 50 mg kg(-1) i.p.) decreased the hippocampal ACh release in both young and old rats. Furthermore, ketamine 50 mg kg(-1) i.p. (anesthetic dose) produced facilitatory effects on the hippocampal ACh release in young rats (193% of the basal release), while in old rats the same dose of ketamine i.p. produced more pronounced facilitatory effects on the hippocampal ACh release (317% of the basal release). On the other hand, propofol 50 mg kg(-1) i.p. (anesthetic dose) produced inhibitory effects on the hippocampal ACh release in young rats (56% of control) and in old rats (77% of control). Although the maximal inhibitory peak effects of propofol 50 mg kg(-1) i.p. did not differ significantly between young rats and old rats, decrease of the hippocampal ACh release in old rats persisted longer than in young rats. CONCLUSION: Ketamine produced more pronounced facilitatory effects on the hippocampal ACh release in old rats, as compared with young rats. On the other hand, propofol has inhibitory effects on the hippocampal ACh release in young and old rats. The aging process may suppress the ability to recover from the inhibitory anesthetic state induced by propofol.

Acetylcholine↗

PubMed2000

Reversal of anticancer drug resistance by macrolide antibiotics in vitro and in vivo.

1. The combined effects of the macrolide antibiotics erythromycin, josamycin, clarithromycin and YM17K (3,4'-dideoxy mycaminosyl tylonolide hydrochloride) on in vitro intracellular accumulation of vinblastine or cyclosporine (Cs)A and on the in vivo antitumour activity of vinblastine were investigated using mouse leukaemia P388 cells (P388/S) and anticancer drug-resistant (P388/ADR) cells. These effects were compared with those of a calcium antagonist (verapamil) or immunosuppressants (FK506 and CsA). 2. All tested macrolide antibiotics increased the accumulation of both vinblastine and CsA in P388/ADR cells in a dose-dependent manner, but their potency was lower than that of verapamil, CsA or FK506. 3. When vinblastine (200 microg/kg) was administered intraperitoneally with each of the macrolide antibiotics (10 or 100 mg/kg) or with verapamil (25 mg/kg) once a day for 10 days in P388/ADR-bearing mice, combined effects of vinblastine with the macrolide antibiotics (erythromycin, clarithromycin and YM17K) or verapamil were observed. 4. The present study suggests that macrolide antibiotics may overcome anticancer drug resistance by inhibiting the binding of vinblastine or CsA to P-glycoprotein in P388/ADR cells. 5. We believe that these results are encouraging for combination chemotherapy to overcome P-glycoprotein-dependent anticancer drug-resistant tumours in clinical practice.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Risk of contralateral manifestation in children with unilateral inguinal hernia: should hernia in children be treated contralaterally?

PURPOSE: This study was done to identify risk factors for metachronous manifestation of contralateral inguinal hernia in patients with unilateral inguinal hernia. METHODS: Characteristics of 156 patients with metachronous contralateral hernia were compared with those of 156 patients with unilateral hernia who were ascertained not to have presented with contralateral hernia. RESULTS: There was a tendency for the hernia to be more often on the left side in 88 of 156 patients (56.4%) with contralateral manifestation compared with 70 of 156 patients (44.9%) in the control group (P =.054). The age at hernia repair of the patients with contralateral manifestation, 1 to 120 months (median, 14 months), was significantly younger than the 1 to 149 months (median, 20 months) of the control patients (P =.016). More patients with contralateral manifestation had a family history of inguinal hernia, and the percentage, 24.4%, was significantly higher than the 14.7% in the control group (P =.046). A univariate analysis with the Cox regression models found that hernia on the left side and a positive family history were significantly associated with the metachronous manifestation of contralateral hernia (hazard ratio [HR], 1.40; P =. 037 and HR, 1.59; P =.013, respectively). CONCLUSION: The risk of metachronous manifestation of contralateral hernia is high in patients with left-side hernia and in those with a family history, and the incidence of contralateral hernia is at most 10% in these patients. The authors think that the incidence is still too low to justify routine exploration and surgery for a patent processus vaginalis. Contralateral exploration should therefore be reserved for high-risk patients in whom second anesthesia and surgery have to be avoided.

Adolescent↗

PubMed2000

The role of the body mass index and triglyceride levels in identifying insulin-sensitive and insulin-resistant variants in Japanese non-insulin-dependent diabetic patients.

Using the minimal model approach shown by Bergman, our group had previously shown 2 variants among non-obese mildly diabetic patients, one with normal insulin sensitivity and the other with insulin resistance. The present study examines whether these 2 variants exist in the ordinary Japanese non-insulin-dependent diabetes mellitus (NIDDM) population and compares the clinical profile between the 2 discrete forms of NIDDM. In addition, we investigated the factors responsible for insulin resistance observed in Japanese NIDDM populations. One hundred eleven untreated Japanese NIDDM subjects (fasting glucose < 10 mmol/L) were assessed for insulin action (homeostasis model assessment [HOMA-IR] = fasting serum insulin (microU/mL) x fasting plasma glucose (mmol/L)/22.5) and the fasting lipid profile. Sixty percent of these patients had normal insulin sensitivity (HOMA-IR < 2.5). The insulin-resistant patients had higher serum cholesterol (188.1 +/- 5.2 v 182.2 +/- 3.9 mg/dL, P> .05) and low-density lipoprotein (LDL) cholesterol (501.2 +/- 16.7 v 469.4 +/- 14.8 mg/dL, P > .05) than the insulin-sensitive patients, but the difference was not statistically significant. In contrast, the former group had a significantly higher body mass index ([BMI] 26.6 +/- 0.8 v 21.7 +/- 0.4 kg/m2, P < .0001) and higher serum triglycerides (181.0 +/- 16.4 (range, 79 to 545) v 95.1 +/- 4.1 (range, 36 to 204) mg/dL, P < .0001) and lower high-density lipoprotein (HDL) cholesterol (47.2 +/- 1.7 v 58.2 +/- 2.5 mg/dL, P < .005) than the latter group. HOMA-IR was related to the BMI. Fifteen of 17 (88%) NIDDM patients with a BMI greater than 27.0 were insulin-resistant, whereas 35 of 38 (92%) NIDDM patients with a BMI less than 21.5 were insulin-sensitive. In the midrange BMI (21.5 to 27.0 kg/m2), patients were equally likely to be insulin-resistant or insulin-sensitive. Analysis of the midrange BMI group showed that HOMA-IR was associated with serum triglycerides (P < .0001) but not with the BMI. These data suggest the following conclusions: (1) Japanese NIDDM patients can be classified into 2 populations, one with normal insulin sensitivity and the other with insulin resistance; (2) NIDDM patients with normal insulin action have a low cardiovascular disease risk factor, whereas those with insulin resistance have a markedly increased cardiovascular disease risk factor; and (3) the BMI and serum triglyceride level per se are associated with insulin action in Japanese NIDDM populations.

Adult↗

PubMed2000

Macrophage proliferation in atherosclerosis.

Oxidized LDL can induce an increase in intracellular calcium concentration and the activation of protein kinase C in mouse peritoneal macrophages. The activation of protein kinase C leads to the release into the culture medium of granulocyte-macrophage colony-stimulating factor, which plays a priming role in oxidized LDL-induced macrophage proliferation. The expression of granulocyte-macrophage colony-stimulating factor in macrophages by oxidized LDL is positively regulated in the 5'-flanking region of granulocyte-macrophage colony-stimulating factor gene from sequence -169 to -160, but negatively regulated from -91 to -82. Granulocyte-macrophage colony-stimulating factor released by oxidized LDL from macrophages induces proliferation in autocrine or paracrine fashion via the activation of phosphatidylinositol 3-kinase. The capacity of oxidized LDL to induce macrophage proliferation in vitro may be involved in the enhanced progression of atherosclerosis in vivo.

Animals↗

PubMed2000

Dimeric inhibin A as a fourth marker for Down's syndrome maternal serum screening in native Japanese women.

OBJECTIVE: This study was conducted to assess the usefulness of dimeric inhibin A as a fourth marker for Down's syndrome screening in addition to AFP, hCG and uE3 markers for native Japanese women. METHODS: Serum specimens from 367 native Japanese women in the second trimester were assayed for dimeric inhibin A levels. Day specific dimeric inhibin A medians were established for gestational ages 15.0-21.9. Weekly median values for the native Japanese were compared with those of a U.S. population. Selected Japanese specimens from 15 diagnosed Down's syndrome and 3 trisomy 18 cases were also assayed for dimeric inhibin A. RESULTS: Dimeric inhibin A levels did not vary greatly over the gestational age range as expected. Median value comparison showed that native Japanese dimeric inhibin A medians are higher than the U.S. population medians by an average of 7.95%. Native Japanese dimeric inhibin A median values in this study are 1.77 times higher in Down's syndrome cases than in unaffected pregnancies. Trisomy 18 dimeric inhibin A levels show no significant difference from the unaffected pregnancies. CONCLUSIONS: This report shows for the first time that dimeric inhibin A can be informative as a fourth marker for Down's syndrome screening in native Japanese women. We expect the addition of dimeric inhibin A to a triple marker protocol will increase the accuracy of predicted risk for all pregnancies screened and increase the detection rate of Down's syndrome affected pregnancies.

Biomarkers↗