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Biomedical subjects

N Nakajima

Publications and source records attributed to N Nakajima.

At least 145 records · Page 8Linked to original sources
PubMed1999

Effects of soybean oil emulsion and eicosapentaenoic acid on stress response and immune function after a severely stressful operation.

OBJECTIVE: To investigate the effects of soybean oil emulsion and oral or enteral administration of eicosapentaenoic acid (EPA) on stress response, cytokine production, protein metabolism, and immune function after surgery for esophageal cancer. SUMMARY BACKGROUND DATA: It has been reported that safflower oil, rich in n-6 polyunsaturated fatty acid (n-6 PUFA), affects the survival rate of septic animals and decreases the immune function. It has also been reported that the administration of fish oil, in contrast, reduces these stress responses and stress-induced immunosuppression. In humans, the effects of soybean oil emulsion and the administration of EPA on stress response and immune function after surgery have not been established. METHODS: Patients who underwent esophagectomy with thoracotomy were divided into three groups. Seven patients were fed by total parenteral nutrition (TPN) with soybean oil emulsion, which accounted for 20% of total calories. Seven patients were given oral or enteral administration of 1.8 g/day EPA, in addition to TPN with soybean oil emulsion. Nine patients served as the control group; these patients received fat-free TPN. Serum interleukin-6 (IL-6), C-reactive protein, concanavalin A (con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation, natural killer cell activity, and stress hormones were measured. RESULTS: The postoperative level of serum IL-6 was significantly higher in the group receiving soybean oil emulsion than in the fat-free group. Oral or enteral supplementation of EPA with soybean oil emulsion significantly reduced the level of serum IL-6 compared with the patients receiving soybean oil emulsion. Con A- or PHA-stimulated lymphocyte proliferation decreased significantly on postoperative day 7 in all groups of patients. The supplementation of EPA with soybean oil emulsion significantly improved the lymphocyte proliferation and natural killer cell activity on postoperative day 21 compared with the group receiving soybean oil emulsion. CONCLUSIONS: Soybean oil emulsion amplifies, and the supplementation of EPA reduces, the stress response and stress-induced immunosuppression.

Eicosapentaenoic Acid↗
PubMed1999

Augmented enhancement of in vitro production of inflammatory cytokines in peripheral blood mononuclear cells in patients undergoing simultaneous resection of the liver and gastrointestinal tract.

OBJECTIVE: To determine changes in the production of inflammatory cytokines and acute-phase proteins, and in the priming of peripheral blood mononuclear cells (PBMC), as mechanisms for the high incidence of postoperative complications in patients who have undergone hepatectomy simultaneously with resection of the gastrointestinal tract. DESIGN: Prospective, clinical study for 3 wks after operation. SETTING: A surgical department in a university hospital. PATIENTS: Twenty-one consecutive adult patients with synchronous and metachronous hepatic metastases from gastrointestinal malignancies, curatively resected by simultaneous resection (group A, n = 9) or by hepatectomy alone (group B, n = 12), and 15 patients with gastrointestinal malignancies undergoing curative resection (group C). INTERVENTION: Peripheral venous blood samples collected before operation and on days 1, 3, 5, 7, 10, 14, and 21 after operation. MEASUREMENTS AND MAIN RESULTS: The serum and plasma levels of acute-phase proteins, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and endotoxin were measured. The in vitro production of IL-1beta and TNF-alpha by PBMC was also determined by the stimulation of lipopolysaccharide. The incidence of postoperative complications was significantly higher in group A than in groups B and C. The serum levels of IL-6 increased significantly, with a peak at postoperative day 1 in all groups, and the peak levels of IL-6 in groups A and B were significantly higher than that in group C. The serum levels of all acute-phase proteins measured in this study (alpha1-antitrypsin, haptoglobin, and C-reactive protein) increased markedly after operation in group C (p < .05). In group A, only C-reactive protein increased after operation, but its peak level was lower than in groups B and C (p < .05). Although IL-1beta and TNF-alpha in the serum were not detectable in any of the groups during the entire study period, the lipopolysaccharide-induced in vitro production of IL-1beta and TNF-alpha by PBMC in all groups was significantly elevated after operation, with a peak at days 1 and 3 after operation, respectively. In addition, the elevation of the in vitro production of IL-1beta and TNF-alpha in group A was significantly greater than that in group C, lasting until postoperative day 5 (IL-1beta) and postoperative day 10 (TNF-alpha). The levels of plasma endotoxin increased significantly in all groups, with a peak at day 1 after operation, and the peak levels were significantly higher in group A than in groups B and C. There was a significant correlation between the peak levels of in vitro TNF-alpha production and the peak levels of plasma endotoxin (r2 = .331, p< .01). CONCLUSIONS: The augmented enhancement of the priming of PBMC as a result of surgery in patients undergoing simultaneous resection of the liver and gastrointestinal tract, together with the reduced synthesis of the acute-phase reactants and impaired host defense mechanisms, might be responsible for the high incidence of postoperative complications, possibly because subsequent exposure of primed macrophages/monocytes to triggering substances such as endotoxin and bacterial components after operation results in inappropriate production of inflammatory cytokines.

Acute-Phase Proteins↗
PubMed1999

[Induction of protective immunity for Bordetella pertussis by nasal inoculation of pertussis vaccine in mice].

Although nasal vaccination has emerged as an interesting alternative to intramuscular or oral vaccination, knowledge is scarce about the immune responses after such immunization. In the present study, we inoculated purified Pertussis Toxin (PT) and Filamentous Haemagglutinin (FHA) with or without adjuvant (kayexalate), or Diphtheria acellular Pertussis Tetanus (DaPT) combined vaccine to mice intranasally three times every four weeks to investigate the references of the immunoresponses between nasal and intramuscular vaccination. The levels of pertussis specific serum IgG antibodies (Abs) and secretory IgA Abs in the nasal wash were measured by ELISA, and cytotoxic T cell activities were examined by proliferative response, and compared with the result from intramuscular inoculation. We also studied the efficacy of adjuvant in the nasal vaccination. The intramuscular inoculation of pertussis vaccine induced serum IgG antibodies and cellular immunity against PT and FHA, but did not induce local IgA antibodies. On the other hand, the nasal inoculation induced both serum and local antibody responses. Moreover, it also induced significant cellular immunity to pertussis antigen. In nasal vaccination, the inoculation with adjuvant was superior to inoculation without adjuvant for the induction of both humoral and cellular immunity.

Animals↗
PubMed1999

Synthetic studies of an 18-membered antitumor macrolide, tedanolide. 5. Stereoselective synthesis of the C13-C23 part via condensation of two fragments, C13-C17 and C18-C21, by taking advantage of the 3,4-dimethoxybenzyl protecting group.

An efficient and stereoselective synthesis of the C13-C23 part (8) was achieved starting from methyl (R)- and (S)-3-hydroxy-2-methylpropionates (9) via coupling of the C13-C17 aldehyde (6), prepared by Evans asymmetric aldol reaction, with the C18-C21 iodoalkene (5b) by taking advantage of the 3,4-dimethoxybenzyl protecting group.

Anti-Bacterial Agents↗
PubMed1999

Synthetic studies of the 18-membered antitumor macrolide, tedanolide. 3. Stereocontrolled synthesis of the C1-C12 part via a synthesis of the C1-C7 fragment by a mismatched but efficient sharpless dihydroxylation and its coupling with the C8-C11 fragment.

The C1-C12 part (4) of tedanolide (1) was synthesized starting from methyl (R)-3-hydroxy-2-methylpropionate (11a) via a coupling between the C1-C7 aldehyde (6) and the C8-C11 iodoalkene (7a). For a synthesis of 6, a mismatched but highly efficient Sharpless dihydroxylation of the alpha, beta-unsaturated ester (15) with AD-mix-alpha was successfully applied. Compound 7a was synthesized using hydrozirconation to the alkyne (32).

Anti-Bacterial Agents↗
PubMed1999

A preliminary study for clinical pharmacokinetics of oral fluorine anticancer medicines using the commercial MRI system 19F-MRS.

These preliminary studies of dynamic natural abundance 19F-magnetic resonance spectroscopy (19F-MRS) on 5-FU based medicines were performed in the human liver using commercial 1.5 T MRI equipment. A single tuned, custom-made circular shape surface coil with a diameter of 15 cm operating at 60 MHz was used for the 19F-MRS study. Localized proton shimming with a whole body coil was performed with adequate volume to include the observing area of the surface coil, and the line width of the water signal was less than 40 Hz. Very different spectroscopic appearance patterns of 5-FU were observed. We examined whether the pharmacokinetics in the liver of orally administered 1-hexylcarbamoyl-5-fluorouracil (HCFU) differ from those of orally administered 5'-deoxy-5-fluorouridine (5'-DFUR). This preliminary study suggested the 19F-MRS technique could be a useful method of evaluating in vivo the metabolism of 5-FU based medicines.

Administration, Oral↗
PubMed1999

Further characterization of earthworm serine proteases: cleavage specificity against peptide substrates and on autolysis.

Cleavage specificity of two fibrinolytic enzymes from Lumbricus rubellus [Nakajima, N., et al., Biosci. Biotechnol. Biochem., 57, 1726-1730 (1993) and 60, 293-300 (1996)] was investigated using beta-amyloid 1-40 and oxidized insulin B-chain as peptide substrates. The serine protease, F-III-2, cleaved the former substrate at six sites, and the latter at five sites. F-II digested them at six and ten, respectively. The cleavage specificity of F-III-2 resembled those of both trypsin and chymotrypsin. F-II had a broader specificity than F-III-2 and preferred also the bonds consisting neutral or hydrophobic amino acids. Furthermore, F-III-2 itself was digested initially on the site of Arg(144)-Tyr(145) to produce two peptide fragments, when it was autolyzed regularly by heating.

Amino Acid Sequence↗
PubMed1999

Multi-enzymatic glucosylation using Eucalyptus UDP-glucosyltransferase coupled UDPglucose-fermentation by bakers' yeast.

The enzymatic synthesis of glucoside compounds using a membrane-associated UDP-glucosyltransferase fraction from Eucalyptus perriniana cultured cells as a water-insoluble catalyst (N. Nakajima, et. al., J. Ferment. Bioeng., 84 (5), pp. 455-460, 1997) has been effectively done by coupling UDPglucose-fermentation by bakers' yeast. For example, beta-thujaplicin (hinokitiol) and p-aminobenzoic acid were converted respectively to their corresponding beta-D-monoglucosides with the conversion rate of around 24-26% by the multi-enzymatic system with UDPglucose as a glucose donor, which is produced by yeast cells from glucose and 5'-UMP. Addition of either cellobiose, a substrate of beta-glucosidase, or DL-1,2-anhydro-myo-inositol, an inhibitor for the enzyme in the reaction mixture, could increased the yield of these beta-D-monoglucosides. This new enzymatic system could also be used for the synthesis of flavonoid glucosides such as isoquercitrin (quercetin 3-O-beta-D-glucoside).

Eucalyptus↗
PubMed1999

Immunohistochemical localization of multispecific renal organic anion transporter 1 in rat kidney.

Renal proximal convoluted tubules have an important role, i.e., to excrete organic anions, including numerous drugs and endogenous substances. Recently, multispecific organic anion transporter 1 (OAT1) was isolated from rat kidney. In this study, the cellular and subcellular localization of OAT1 in rat kidney was investigated. Kidneys from normal rats were perfused and fixed with periodate-lysine-paraformaldehyde solution and were then processed for immunohistochemical analysis using the labeled streptavidin-biotin method, preembedding horseradish peroxidase method, and immunogold method. Light microscopic examination revealed immunostaining for OAT1 in the middle portion of the proximal tubule (S2 segment), but not in the initial portion of the proximal convoluted tubule, next to the glomerulus. Nephron segments other than the S2 segment and the renal vasculature were not stained with antibody to OAT1. Electron-microscopic observation using a preembedding method revealed that OAT1 was exclusively expressed in the basolateral membrane of S2 segments of proximal tubules. The immunogold method showed no labeling for OAT1 in the cytoplasmic vesicles, suggesting that OAT1 may not move together with organic anions into the cells. These results are consistent with previous physiologic data showing that organic anions, including para-aminohippurate, are taken up by the basolateral Na+-independent organic anion/dicarboxylate exchanger and excreted at S2 segments. In conclusion, OAT1 was localized to the basolateral membrane of S2 segments of proximal tubules in rat kidneys.

Animals↗
PubMed1999

[Biological properties of T6S cells, a clone of burn-associated type 2 T cells].

A clone of type 2 T cells (T 6 S cell) was established from burn-associated CD 8+ CD 11 b+ TCR gamma/delta + type 2 T cells, and their biological properties were examined. After stimulation by anti-CD 3 monoclonal antibody (mAb), T 6 S cells produced IL-4 and IL-10 into their culture fluids. However, IFN-gamma and IL-2 were not demonstrated in the culture fluids of T 6 S cells stimulated with the mAb. The susceptibility of thermally injured mice to infection with herpes simplex virus type 1 (HSV-1) or Candida albicans (C. albicans) has been shown to be approximately 50 (C. albicans) to 100 (HSV-1) times greater than that of normal mice. As compared with the resistance of thermally injured mice to these pathogens, mice inoculated with 1 x 10(6) cells/mouse of T 6 S cells (designated as T 6 S-mice) showed the same susceptibility to the infections. When T 6 S-mice treated with a mixture of monoclonal antibodies (mAbs) directed against IL-4 and IL-10 were infected with a lethal dose of HSV-1 or C. albicans, their resistance to these pathogens was restored to levels found in normal mice. From the experiments using T 6 S-mice, it is suggest that type 2 T cells or their cytokine products (IL-4 and IL-10) may play an important role on the impaired resistance of thermally injured mice to certain opportunistic pathogens. T 6 S cell may be a useful tool to study opportunistic infections in hosts bearing type 2 T cells.

Animals↗
PubMed1999

Unresponsiveness to glibenclamide during chronic treatment induced by reduction of ATP-sensitive K+ channel activity.

The insulin response to the sulfonylurea glibenclamide was markedly impaired in pancreatic beta-cell line MIN6 cells with chronic glibenclamide treatment (MIN6-Glib). The intracellular calcium concentration increased only slightly in response to glibenclamide in MIN6-Glib. While the properties of the voltage-dependent calcium channels were not altered, the conductance of the K(ATP) channels, the primary target of glibenclamide, was significantly reduced in MIN6-Glib. The ATP-sensitive K+ (K(ATP)) channels in MIN6 cells comprise inwardly rectifying K+ channel member Kir6.2 subunits and sulfonylurea receptor (SUR) 1 subunits. MIN6 cells have both high- and low-affinity binding sites for glibenclamide. The binding affinities at these two sites were unchanged, but the maximum binding capacities at both sites were similarly increased by chronic glibenclamide treatment. Both SUR1 and Kir6.2 mRNA levels were not altered, but SUR1 protein was rather increased in MIN6-Glib. In addition, electron microscopic examination revealed a majority of the SUR1 to be present in a cluster near the plasma membrane in control MIN6, while it tends to be distributed in the cytoplasm in MIN6-Glib. These data suggest that chronic glibenclamide treatment causes the defect in acute glibenclamide-induced insulin secretion by reducing the number of functional K(ATP) channels on the plasma membrane of the beta-cells.

ATP-Binding Cassette Transporters↗
PubMed1999

Protease activity induced by nicotine in human cells.

Nicotine has a wide range of biological effects, and proteases have been extensively studied for their biological roles in living creatures. The aim of this study is to determine whether nicotine can induce proteolytic protease activity in cultures of various human cell lines. Plasminogen activator-like fibrinolytic protease activity, using 125I-fibrin as substrate in the presence of plasminogen, was estimated in cells with and without nicotine treatment. Among 16 cell lines tested, APr-1 cells were found to have the highest induced protease activity. Partial purification of the proteases was carried out by high performance liquid chromatography gel filtration on TSKG2000SW. Protease inhibitor tests indicated that the proteases induced by nicotine are serine proteases.

Cell Line↗
PubMed1999

[A case of central retinal vein occlusion forming the epiretinal membrane].

BACKGROUND: We encountered a patient with central retinal vein occlusion (CRVO) forming an epiretinal membrane (ERM) in a wide area. Generally formation of ERM is rare in CRVO. PATIENT AND METHODS: The patient was a 72-years-old female with ischemic CRVO in the right eye, who had undergone insufficient pan-retinal photocoagulation. Since ERM was formed in a wide area 7 months after the occurrence of CRVO, the patient underwent vitrectomy. RESULTS: Although the patient was elderly, the posterior vitreum had not been detached, and ERM was observed in a wide area from the disk of the optic nerve over the vascular arcade. Since the ERM strongly adhered to the retina, incision of the membrane with vitreous scissors was required. The membrane tissue collected during the operation showed few vascular and cellular components, and consisted of ERM extracellular matrices such as collagen. CONCLUSIONS: In this patient, however, it was probable that not only barrier dysfunction of retinal vessel endothelial cells caused by elevated pressure in the retinal vein and rapid retinal ischemia but also the anatomical feature of the undetached posterior vitreum was involved in the formation of the ERM.

Aged↗
PubMed1999

Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes.

Organic anion transporter 1 (OAT1) is the para-aminohippurate (PAH) transporter in the basolateral membrane of the proximal tubule. The present study investigated whether or not nonsteroidal anti-inflammatory drugs (NSAIDs) are transported by OAT1. All of the NSAIDs tested inhibited [14C]PAH uptake via OAT1 expressed in Xenopus laevis oocytes. Ibuprofen, indomethacin, salicylurate, and naproxen showed the strongest potency to inhibit [14C]PAH uptake (Ki approximately 2-10 microM); acetylsalicylate, salicylate, and phenacetin exhibited moderate potency (Ki approximately 300-400 microM), and acetaminophen (paracetamol) exhibited the weakest inhibitory potency (Ki approximately 2 mM). Radiolabeled acetylsalicylate, salicylate, and indomethacin were taken up by OAT1 and the uptake rate of these three NSAIDs was enhanced by the outwardly directed dicarboxylate gradient. The efflux of the preloaded [14C]PAH from the oocytes via OAT1 was trans-stimulated by PAH and glutarate added to the media. The addition of salicylate, acetylsalicylate, or salicylurate into the media also trans-stimulated the efflux of PAH, whereas indomethacin did not. The present study indicates that OAT1 is responsible for the renal uptake and secretion of NSAIDs.

Animals↗
PubMed1999

GnRH agonist for intravenous leiomyomatosis with cardiac extension. A case report.

BACKGROUND: Intravenous leiomyomatosis with cardiac extension is an extremely rare disease. CASE: We recently treated a case of intravenous leiomyomatosis with extension from the inferior vena cava into the right atrium. Three operations--exploratory laparotomy, debulking of the pelvic mass and resection of the intracardiac leiomyoma--were performed. Since cells of the resected leiomyomatosis were estrogen receptor positive, we postoperatively administered GnRH agonist (leuprorelin acetate) for six months to prevent regrowth of the residual mass in the pelvis. The residual mass began to enlarge immediately after cessation of leuprorelin acetate. The same medication was readministered, and regrowth of the residual mass was completely inhibited for 15 months, until this writing. CONCLUSION: Intravenous leiomyomatosis seems to be hormone dependent, as in the case of uterine leiomyomas. In the absence of total resection, functioning ovarian tissue may remain. Therefore, long-term treatment with GnRH agonist may be useful in preventing recurrence of this disease.

Adult↗