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Biomedical subjects

Masataka Nakamura

Publications and source records attributed to Masataka Nakamura.

At least 37 records · Page 2Linked to original sources
PubMed2004

Catheter-related infections in continuous hemodiafiltration in intensive care patients.

BACKGROUND/AIMS: Infection control is of key importance especially in the application of long-term continuous hemodiafiltration (CHDF) involving invasive vascular catheterization to critically ill patients. We investigated hemodialysis catheter-related infections in long-term CHDF. METHODS: We examined catheter infections in 54 patients who were admitted to the intensive care unit and underwent CHDF for 2 weeks or longer. RESULTS: With a total of 155 catheters (1,071 catheter days) studied, catheter colonization and catheter-related bloodstream infection were noted with an incidence rate of 4.8 and 2.7 per 1,000 catheter days, respectively. No difference in catheter colonization rate was observed depending on the catheterization sites or duration of catheterization. Infections were identified in 39 patients (72%) and blood culture positivity was noted in 25 patients (46%). CONCLUSIONS: Since the majority of cases requiring long-term CHDF are complicated with a variety of infections, it is difficult to control infections associated with hemodialysis catheters separately from infections of other types. Systemic infection control should serve as a strategy finally leading to successful control of catheter-related infection.

Catheterization↗
PubMed2004

Effects of prostaglandin D2 on helper T cell functions.

Prostaglandin (PG) D(2) is abundantly produced by mast cells in the sites of allergic inflammations and acts on various cell types through its receptors DP and CRTH2. Among human T cells, CRTH2 is preferentially expressed on Th2-type cells. However, distribution of DP among T cells and impacts of CRTH2- and DP-mediated signals on T cell functions are presently unclear. Here, we show that CD4(+) and CD8(+) T cells producing IFN-gamma and IL-2 were reduced by DP-mediated signals, while CRTH2-mediated signals enhanced IL-2, IL-4, IL-5, and IL-13 production by Th2 cells. CRTH2 signals also caused up-regulation of CD11b and CD40L in resting Th2 cells. RT-PCR analysis revealed distribution of DP among Th cell subsets. On CRTH2(+) Th2 cells, the CRTH2-mediated PGD(2) effects were dominantly observed. Thus, PGD(2) favors Th2 functions through CRTH2 while restraining Th1 functions via DP, which may contribute to development of Th2-dominated status in allergic inflammations.

Cells, Cultured↗
PubMed2004

Partial liquid ventilation with FC-77 suppresses the release of lipid mediators in rat acute lung injury model.

OBJECTIVE: To investigate whether the release of lipid mediators is suppressed in rats with experimentally induced acute lung injury managed with partial liquid ventilation (PLV) using FC-77. DESIGN: Prospective, randomized controlled study. SETTING: Research laboratory in a university. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: After tracheostomy was performed under general anesthesia, lung injury was induced by intratracheal instillation of HCl. The PLV group was then subjected to conventional gas ventilation for 30 mins, followed by PLV using FC-77. The control group was subjected to conventional gas ventilation throughout the study period. MEASUREMENTS AND MAIN RESULTS: In the PLV group the following results were obtained: a) impaired oxygenation was markedly improved; b) the increase in the serum levels of lipid mediators such as leukotriene B4, thromboxane A2, and 6-keto-prostaglandin F1alpha was suppressed; and c) the increase in the concentrations of leukotriene B4, thromboxane A2, and 6-keto-prostaglandin F1alpha in the total lung homogenate at 180 mins after lung injury was also suppressed. CONCLUSION: This study indicates that PLV using FC-77 suppresses the release of lipid mediators in our rat model of acute lung injury. However, further investigation is needed to clarify the precise mechanism of this effect.

6-Ketoprostaglandin F1 alpha↗
PubMed2004

Continuous hemodiafiltration in pediatric critical care patients.

Continuous hemodiafiltration (CHDF) is an essential procedure in critical care. However, application of this therapy to pediatric patients is associated with several problems derived from their smaller body size and weight compared with adults. We have successfully conducted CHDF in pediatric patients including newborns by taking such problems into consideration and carefully coping with them. The present study consisted of 60 pediatric patients treated with CHDF. Clinical efficacy and safety of CHDF in pediatric patients were assessed in these patients by reviewing patient clinical records. The 60 patients treated with CHDF included 27 males and 33 females. Their body weight ranged from 700 g to 53.0 kg. The mean CHDF duration was 6.80 +/- 6.94 days. Blood access was provided in a veno-venous mode in 42 patients, and an arterio-venous mode in 18 patients. Of the 60 pediatric patients receiving CHDF, 31 patients survived without serious complications, achieving a survival rate of 51.7%. Successful CHDF in pediatric patients was achieved by careful and exact execution of the following countermeasures to overcome problems specific to application of this therapy to pediatric patients: minimization of the priming volume; use of colloid solutions or whole blood as priming solution; maintaining secure blood access; selection of an appropriate anticoagulant; temperature control of both the patient's body and components of the hemofiltration circuit. In pediatric critical care, CHDF is safely applicable to the critically ill and expected to produce a wide spectrum of clinical efficacy just as in adults.

Adolescent↗
PubMed2004

Modulation of polymorphonuclear leukocyte apoptosis in the critically ill by removal of cytokines with continuous hemodiafiltration.

Delay of polymorphonuclear leukocyte (PMN) apoptosis caused by hypercytokinemia is considered to be a potential cause of tissue damage and resultant organ failure. We evaluated whether continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF), which can remove cytokines in the circulating blood, can modulate apoptosis in peripheral blood neutrophils and thereby reduce tissue damage and organ dysfunction in 25 critically ill patients. Following the completion of a 3-day PMMA-CHDF session, serum cytokine levels were significantly decreased and the percentage of apoptotic PMNs was significantly increased. A significant correlation was observed between the PMMA-CHDF-induced increase in the percentage of apoptotic PMNs and the degree of decrease in the serum interleukin-6 level. A significant correlation was also found between the increase in the percentage of apoptotic PMNs and improvement in sequential organ failure assessment score following PMMA-CHDF. These results suggest that PMMA-CHDF in critically ill patients with hypercytokinemia and concomitant delay in apoptosis of PMNs can alleviate the delay of PMN apoptosis through the removal of serum cytokines and thus may result in avoidance of organ dysfunction.

Adult↗
PubMed2003

Gene structure and functional properties of mouse CRTH2, a prostaglandin D2 receptor.

CRTH2, the second receptor for prostaglandin D(2) (PGD(2)), is thought to play a role in allergic inflammations through the induction of chemotactic migration and/or the activation of Th2, eosinophils, and basophils, in humans. We previously identified the mouse CRTH2 homolog of human CRTH2 and suggest that animal models would provide a clear understanding on the precise function of CRTH2 in allergic disorders. To this end we have confirmed that mouse CRTH2 is similar in gene structure to human CRTH2 and revealed that mouse CRTH2 is predominantly expressed in the eosinophils derived from IL-5-transgenic mice. Moreover, mouse CRTH2 harbors the ability to bind PGD(2) with high affinity and intracellular Ca(2+) mobilization in a Gi-dependent manner and chemotactic responses in several transfected cell lines. The results demonstrated here indicate that mouse CRTH2 is the functional ortholog of human CRTH2 and paves the way for future analysis of the in vivo functions of CRTH2.

Animals↗
PubMed2003

Granulysin in human serum as a marker of cell-mediated immunity.

Granulysin is a cytolytic granule protein of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) with a broad range of antimicrobial and tumoricidal activities. Two molecular forms of granulysin, the 15-kDa precursor and 9-kDa mature form, are produced in these cells. In this study, we developed monoclonal antibodies against granulysin and found that the 15-kDa granulysin is spontaneously secreted by peripheral blood NK and T cells via a non-granule exocytotic pathway. When NK cells killed the target cells, the released granulysin levels in culture supernatants significantly increased through the granule exocytosis. The granulysin protein was found in the sera of healthy individuals at an average concentration of 3.7 +/- 3.2 ng/ml (age 0-99 years, n=244). The serum levels of granulysin were transiently highly elevated among patients with acute viral infections. In addition, the serum granulysin levels in patients with severe immunodeficiency treated bycell therapy fluctuated proportionately to the improvement of other immunological parameters. Our results suggest that granulysin is well associated with diverse activities of NK cells and CTL in physiological and pathological settings and could be a useful novel serum marker to evaluate the overall status of host cellular immunity.

Antibodies, Monoclonal↗
PubMed2003

The change in renal replacement therapy on acute renal failure in a general intensive care unit in a university hospital and its clinical efficacy: a Japanese experience.

The aim of our study was to examine renal replacement therapies (RRT) that have been used for acute renal failure (ARF) in our intensive care unit (ICU) patients and to compare their outcomes. Sixteen patients who underwent intermittent hemodialysis (IHD), 14 patients who underwent continuous hemofiltration (CHF) in combination with IHD (CHF + IHD), and 38 patients who underwent continuous hemodiafiltration (CHDF) were evaluated. Regarding the effects of blood purification on hemodynamics and renal function, the percentage increase in blood pressure and percent rapid increase in urinary output were the greatest in the CHDF group. The hourly urinary output after the start of initial blood purification increased only in the CHDF group. The survival rate was significantly higher in the CHDF group. These results suggest that CHDF should be the first-line therapy for patients with ARF and that we are moving in the right direction regarding the application of RRT to treat ARF in ICU patients.

Acute Kidney Injury↗
PubMed2003

Induction of protective immune responses against R5 human immunodeficiency virus type 1 (HIV-1) infection in hu-PBL-SCID mice by intrasplenic immunization with HIV-1-pulsed dendritic cells: possible involvement of a novel factor of human CD4(+) T-cell origin.

The potential of a dendritic cell (DC)-based vaccine against human immunodeficiency virus type 1 (HIV-1) infection in humans was explored with SCID mice reconstituted with human peripheral blood mononuclear cells (PBMC). HIV-1-negative normal human PBMC were transplanted directly into the spleens of SCID mice (hu-PBL-SCID-spl mice) together with autologous mature DCs pulsed with either inactivated HIV-1 (strain R5 or X4) or ovalbumin (OVA), followed by a booster injection 5 days later with autologous DCs pulsed with the same respective antigens. Five days later, these mice were challenged intraperitoneally with R5 HIV-1(JR-CSF). Analysis of infection at 7 days postinfection showed that the DC-HIV-1-immunized hu-PBL-SCID-spl mice, irrespective of the HIV-1 isolate used for immunization, were protected against HIV-1 infection. In contrast, none of the DC-OVA-immunized mice were protected. Sera from the DC-HIV-1- but not the DC-OVA-immunized mice inhibited the in vitro infection of activated PBMC and macrophages with R5, but not X4, HIV-1. Upon restimulation with HIV-1 in vitro, the human CD4(+) T cells derived from the DC-HIV-1-immunized mice produced a similar R5 HIV-1 suppressor factor. Neutralizing antibodies against human RANTES, MIP-1alpha, MIP-1beta, alpha interferon (IFN-alpha), IFN-beta, IFN-gamma, interleukin-4 (IL-4), IL-10, IL-13, IL-16, MCP-1, MCP-3, tumor necrosis factor alpha (TNF-alpha), or TNF-beta failed to reverse the HIV-1-suppressive activity. These results show that inactivated HIV-1-pulsed autologous DCs can stimulate splenic resident human CD4(+) T cells in hu-PBL-SCID-spl mice to produce a yet-to-be-defined, novel soluble factor(s) with protective properties against R5 HIV-1 infection.

AIDS Vaccines↗
PubMed2003

[Humoral mediators in the pathophysiology of organ dysfunction in sepsis].

It is recognized that various humoral mediators, especially inflammatory cytokines such as tumor necrosis-factor-alpha and interleukin (IL)-1 beta, play a key role in the pathophysiology of septic shock and organ dysfunction following severe infection. We have recently begun to employ a rapid measurement system that allows us to measure blood IL-6 levels within 30 min using a chemiluminescent enzyme immunoassay. IL-6 blood levels reflect well the activation of the cytokine cascade and correlated well with the severity of patient's, condition. The ratio of simultaneously measured IL-6 blood levels in peripheral and pulmonary arteries is useful to identify the site responsible for cytokine production. Early initiation of PMMA-CHDF as a cytokine modulator of septic shock results in improved recovery from shock and in improved outcome. Genetic analysis of cytokine-related genes revealed a high frequency of a specific genotype in patients who have extremely high IL-6 blood levels. Screening of patients at high risk of hypercytokinemia with the specific genotype would enable appropriate treatments and contribute to future tailor-made medicine.

Cytokines↗
PubMed2002

Basic helix-loop-helix transcription factor epicardin/capsulin/Pod-1 suppresses differentiation by negative regulation of transcription.

Epicardin/capsulin/Pod-1, expressed in skeletal myoblasts within brachial arches and in the condensing mesenchyme, is a member of the basic helix-loop-helix (bHLH) transcription factor family that is involved in various cell differentiation processes. In this study, we examined the functional properties of epicardin/capsulin/Pod-1 in differentiation. The yeast and mammalian two-hybrid systems showed physical associations between epicardin/capsulin/Pod-1 and E2A, both of which were present in the nuclei. The bHLH domains mediated this association. Ectopic expression of epicardin/capsulin/Pod-1 inhibited E2A-dependent activation of the exogenous and endogenous expression of the cyclin-dependent kinase inhibitor, p21(WAF1/Cip1) gene, and the muscle creatine kinase gene that encodes the predominant creatine kinase isoform expressed in mammalian skeletal muscle. Transfection with epicardin/capsulin/Pod-1 small interfering RNA abolished the epicardin/capsulin/Pod-1-mediated suppression of E12-dependent activation of the p21 promoter. Chromatin immunoprecipitation assay showed that epicardin/capsulin/Pod-1 was physically associated with the muscle creatine kinase promoter in vivo. Moreover, terminal differentiation of C2C12 myoblasts was inhibited by exogenous introduction of epicardin/capsulin/Pod-1. These inhibitory functions of epicardin/capsulin/Pod-1 closely resemble those of the bHLH inhibitor Twist protein. These results indicate that epicardin/capsulin/Pod-1 functions as a negative regulator of differentiation of myoblasts through transcription in at least two distinct steps, cell growth arrest and lineage-specific differentiation.

Animals↗
PubMed2002

Cutting edge: agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2.

Indomethacin is a widely used nonsteroidal anti-inflammatory drug and is generally known to exhibit its multiple biological functions by inhibiting cyclooxygenases or activating peroxisome proliferator-activated receptors. In this study, we present evidence demonstrating that the novel PGD(2) receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) is another functional target for indomethacin. Indomethacin induced Ca(2+) mobilization in CRTH2-transfected K562 cells at submicromolar concentrations (approximate EC(50), 50 nM) in a G(alphai)-dependent manner as PGD(2) did. Other nonsteroidal anti-inflammatory drugs (aspirin, sulindac, diclofenac, and acemetacin) had no such effect even at micromolar concentrations. In chemotaxis assay, three CRTH2-expressing cell types, Th2 cells, eosinophils, and basophils, were all significantly attracted by indomethacin (EC(50), 50-500 nM) as well as by PGD(2) (EC(50), 2-20 nM), and the effects of indomethacin were blocked by anti-CRTH2 mAb. These results suggest the involvement of CRTH2 in mediating some of therapeutic and/or unwanted side effects of indomethacin, independently of cyclooxygenases and peroxisome proliferator-activated receptors.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Distributions of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict pregnancy outcome following recurrent abortion.

PROBLEM: To evaluate the ability of immunophenotypes of endometrial leukocytes from patients with histories of recurrent abortion to predict outcome of subsequent pregnancy. METHODS OF STUDY: Seventeen women with two successive spontaneous abortions with normal karyotype in the conceptus and 15 women with male-factor infertility were studied. Subsequent pregnancy outcomes in 17 recurrent abortion patients were noted; 11 had live birth, while six aborted in the first trimester. All of 15 women with male-factor infertility became pregnant after therapy, resulting in live birth in all cases. Endometrium was sampled during the peri-implantation period before subsequent pregnancy. We immunostained paraffin-embedded sections for lymphocyte markers including natural killer (NK) cell markers, CD56 and CD16, a B-cell marker CD20, T-cell markers CD3 and CD8, and a specific T-helper(Th)2 and T-cytotoxic (Tc)2 marker termed 'chemoattractant receptor-homologous molecule expressed on Th2 cells' (CRTH2). Immunoreactive cells for these antigens were counted and positivity ratios to CD45- or CD3-positive cells were calculated. These parameter were compared between 17 patients with histories of recurrent abortion and 15 control women and also compared between 11 patients whose subsequent pregnancy was successful and six patients whose subsequent pregnancy was a failure. RESULTS: Numbers of CD45+, CD56+, CD16+, CD20+, CD3+, CD8+, and CRTH2+ cells in recurrent abortion patients resembled those in controls. No significant difference in lymphocyte subset numbers or ratios was noted between patients whose subsequent pregnancy was successful and those who again aborted. CONCLUSION: We could not predict pregnancy outcome by immunophenotypic analysis of endometrium in women with recurrent abortion.

Abortion, Habitual↗
PubMed2002

Interleukin 2 receptor gamma chain (gamma(c)) knockout mice show less regularity in estrous cycle but achieve normal pregnancy without fetal compromise.

PROBLEM: Implication of cytokines in pregnancy suggested but remains to be established. We studied the effect of cytokines on reproductive functions such as ovulation and pregnancy, with mutant mice lacking interleukin 2 receptor gamma (IL-2Rgamma), the so-called common gamma chain (gamma(c)), which is shared among receptors for multiple cytokines such as IL-2, IL-4, IL-7, IL-9 and IL-15. METHOD OF STUDY: Regularities of estrous cycles were observed by vaginal smear. Ovaries stimulated with postmenopausal serum gonadotropin (PMSG) were examined for the ovarian capacities. The uteri at 13 days of gestation were used for histological analysis of the maternal-fetal interface. RESULTS: The estrous cycles in gamma(c) knockout (gamma(c) KO) mice were irregular compared with wild-type mice, although, the mutants could become pregnant. No uterine natural killer (uNK) cell was found in the uterus at 13 days of pregnancy, and poor decidual formation and thickness of blood vessel walls were observed. Apparent differences were not seen in the numbers and weight of the fetuses between wild type and mutant animals, and fetuses were not compromised throughout pregnancy. CONCLUSIONS: The gamma(c) KO mice showed irregular estrous cycle but they could carry out normal pregnancy despite lacking uNK and cytokines actions of IL-2, 4, 7, 9 and 15.

Animals↗
PubMed2002

Accumulation of CD16+ cells with secretion of Ksp37 in decidua at the end of pregnancy.

PROBLEM: Maternal cellular immunity is thought to be in a state of tolerance during pregnancy, but the precise mechanism of immunomodulation is not yet known. We investigated a novel serum protein, killer-specific secretory protein of 37 kDa (Ksp37), produced by cytotoxic lymphocytes, during pregnancy. METHOD OF STUDY: The level of Ksp37 was determined by enzyme linked immunosorbent assay (ELISA) in the sera of healthy pregnant women. Intracellular Ksp37 expression in mononuclear cells, isolated from peripheral blood and decidua at parturition, was examined with a flow cytometer. RESULTS: Serum Ksp37 levels significantly increased at late pregnancy, compared with non-pregnant controls and the first trimester of pregnancy. The flow cytometric analysis exhibited that Ksp37 was mainly expressed in CD16+ natural killer (NK) cells in decidua of term placenta. CONCLUSIONS: Serum Ksp37 level was elevated at late gestational period. CD16+ NK cells in decidua seem to be a main maternal source of Ksp37. Innate immunity, with CD16+ NK cells, may play important roles near parturition.

Adult↗
PubMed2002

Continuous hemofiltration/hemodiafiltration in critical care.

Continuous hemofiltration and continuous hemodiafiltration (CHF/CHDF) were developed as continuous renal replacement therapy for patients with severe conditons and has come to be widely performed mainly in critical care, taking the place of intermittent hemodialysis. The membrane pore size of a hemofilter used for CHF/CHDF allows passage of substances ranging from 30,000 to 50,000 Da, and the method for solute removal in CHF/CHDF employs the principle of convection, which is advantageous for removing middle- to high-molecular-weight substances. As apheresis therapy to remove pathogenic substances in blood, CHF/CHDF is therefore being investigated for its possible effect on various morbid conditions. It has recently been found that CHF/CHDF removes humoral mediators including cytokines, particularly in severe systemic inflammatory response syndromes such as septic shock and severe acute pancreatitis. CHF/CHDF is thus beginning to be performed for the prevention and treatment of organ dysfunction secondary to septic shock, trauma, or acute pancreatitis. CHF/CHDF is also efficacious as artificial liver support in preventing adverse effects caused by plasma exchange (PE) and for continuous removal of hepatic coma-inducing substances. CHF/CHDF is effective for various morbid conditions not only as renal replacement therapy, but also as apheresis therapy and is expected to be applied more widely in critical care in the future.

Critical Care↗
PubMed2002

Long-term survivors with artificial liver support in fulminant hepatic failure.

Clinical ability of artificial liver support (ALS) has been improved greatly in recent years which has allowed us to encounter long-term survivors with fulminant hepatic failure (FHF) whose liver function has been almost completely lost. This suggests that application of ALS in patients with FHF gains time while awaiting transplantation as well as time for functional recovery and regeneration of the liver graft following receipt of the graft with marginal function and/or size. Thus, ALS will contribute greatly to extending the indications for liver transplantation and increase the number of patients receiving and benefiting from this treatment. On the other hand, introduction of ALS prolongs the duration of intensive treatment which increases the risk of infection and increases medical costs. In addition, when to discontinue intensive treatment of patients whose level of consciousness is maintained only by ALS is controversial. Thus, further investigation will be needed to establish a consensus on indications for long-term ALS in FHF.

Adult↗