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Biomedical subjects

N Nagao

Publications and source records attributed to N Nagao.

At least 19 recordsLinked to original sources
PubMed2001

The relationship between UVB screening and cytoprotection by microcorpuscular ZnO or ascorbate against DNA photodamage and membrane injuries in keratinocytes by oxidative stress.

Decreased cell viability and increased formation of cyclobutane-type pyrimidine dimers (CPDs) in DNA of UVB-irradiated keratinocytes were shown to be appreciably restored by the addition of w/o emulsion of microcorpuscular zinc oxide (mcZnO) with a corpuscle diameter of 0.15 microm. The cytoprotection was exerted only by 20 wt/wt% mcZnO at levels equivalent to 40- to 100-microm-thick emulsion layers, which screened 90-92% of the incident UVB. However, protection was not seen by mcZnO below 20-microm thickness, which, unexpectedly, screened 79% of the incident radiation. This suggests that thorough UVB screening is necessary for cytoprotection. This may be attributable to involvement of intracellular reactive oxygen species (ROS) secondarily generated from UVB-irradiated mcZnO. Intracellular ROS was increased in mcZnO-added cells in a time-dependent manner even after UVB irradiation, contrasting with reduction of intracellular ROS in ascorbic acid-added cells. UVB-induced disruption of cell membrane integrity was reduced by mcZnO at 100-microm thickness, equivalent to the addition of ascorbic acid of 50 microM. Thus, mcZnO was thought to be cytoprotective through reductions of intracellular ROS generation, CPD formation and cell membrane disintegration when added so abundantly so as to achieve UVB-screening more than 90%.

Animals↗
PubMed2001

Primary refractoriness to platelet transfusion caused by Nak(a) antibody alone.

BACKGROUND AND OBJECTIVES: Anti-Nak(a), a platelet-specific antibody, occasionally causes platelet-transfusion refractoriness (PTR) together with human leucocyte antigen (HLA) antibodies. Anti-Nak(a) usually appears after frequent platelet transfusions or pregnancy. We report the first case of PTR caused by anti-Nak(a) alone. MATERIALS AND METHODS: A 19-year-old male patient with testicular tumour showed PTR when receiving his first transfusion of platelets. Screening for platelet antigens and platelet antibodies revealed that he had type I CD36 (Nak(a)) deficiency and that anti-Nak(a), but not anti-HLA, was present before he received his first transfusion. RESULTS: The transfusion of Nak(a)-negative, but HLA non-selected, platelets was effective in raising the platelet count. CONCLUSION: Clinically significant Nak(a) antibody was present as naturally occurring antibody in a platelet glycoprotein IV (CD36)-negative non-transfused male patient.

Adult↗
PubMed2000

Tumor invasion is inhibited by phosphorylated ascorbate via enrichment of intracellular vitamin C and decreasing of oxidative stress.

Tumor metastasis and invasion were shown to be inhibited by the 2-O-phosphorylated form (Asc2P) of L-ascorbic acid (Asc); intact Asc did not inhibit tumor invasion when added once, but appreciably inhibited it upon repeated addition. The anti-metastatic effect is attributable to a marked enrichment of intracellular Asc by Asc2P, subsequently dephosphorylated. Asc2P scavenged most of the intracellular reactive oxygen species (ROSin), and notably inhibited production of matrix metalloproteases and cell motility. ROSin was decreased by Asc2P more markedly than by Asc added once. Thus, involvement of ROSin in tumor invasion and a potent anti-metastatic therapy by ROSin-decreasing agents are suggested.

Animals↗
PubMed2000

Enhanced invasion of Tax-expressing fibroblasts into the basement membrane is repressed by phosphorylated ascorbate with simultaneous decreases in intracellular oxidative stress and NF-kappa B activation.

Invasion of rat fibroblastic cells Rat-1 through Matrigel was shown to be promoted by transfection with tax gene of human T-cell leukemia virus type 1. We found that an oxidation-resistant type of vitamin C (Asc), Asc-2-O-phosphate (Asc2P), inhibited the invasion of the tax-transfected Rat-1 cells (W4 cells). Intracellular Asc (Ascin), after enzymatic dephosphorylation of administered Asc2P, was more abundant in W4 cells than in Rat-1 cells, and the ratio of dehydroascorbic acid versus Asc was increased in W4 cells but scarcely in Rat-1 cells, according to the enhanced level of intracellular reactive oxygen species (ROSin) in W4 cells. Asc2P notably repressed the increases in both ROSin and secretion of matrix metalloproteases (MMPs), but did not affect Tax protein expression in tax-transfectants. NF-kappa B activation, as evidenced by its translocation to the nucleus in W4 cells, was also repressed by Asc2P. Thus, the tax-promoted invasion together with the enhanced production of MMPs occurred with NF-kappa B activation and the increase in ROSin, both of which were effectively reduced by Asc2P. These findings indicate the therapeutic efficacy of Ascin-enriching agents for the prevention against tumor invasion in which ROSin plays a major role.

Animals↗
PubMed2000

[Evaluation of antiretroviral chemotherapy based on the profile of virus isolation from HIV-1 infected individuals].

It is well-known that the biological characteristics of HIV-1 persistently infected in the host have often changed into a rapid growth in vitro, T-cell line tropism and marked syncytium inducing (SI) ability accompanied by the progress of clinical stages from AC to ARC or AIDS. We have developed a follow-up diagnostic test using the clinical markers based on the virus phenotypes mentioned above, and reported that the test was significantly useful for determining the clinical status of HIV infected individuals. Recently, highly active antiretroviral therapy (HAART) was introduced into HIV-1 chemotherapy, and has been reported to be a markedly effective treatment for HIV infected individuals. In this study, we carried out an investigation to see whether the follow-up diagnosis was useful even after introducing the HAART in Japan in 1997. The results by the laboratory diagnosis on 139 HIV infected individuals who were clinically observed over a long period showed that the positive rate of virus isolation and MT-4 cell tropism in the isolates during the two years between 1997 and 1998 were significantly lower than that of the nine years from 1988 to 1996 before the implementation of HAART. In addition, we obtained data that the effect of HAART reflects the biological profiles of virus isolation more than the CD4+ T cell counts. These results suggest that data of clinical examination using virus isolation as a parameter are useful not only for predicting the development of AIDS but also for evaluating the effects of HAART, particularly in patients showing no association between the CD4+ T cell counts and the plasma viral load.

Acquired Immunodeficiency Syndrome↗
PubMed1999

[Vitamin C: structure-activity correlation and cytoprotective actions through free radical scavenging and extracellular matrix construction].

Conventional studies on vitamin C have been conducted by single-dosage administration with ascorbic acid itself being so labile as to undergo irreversible degradation. In contrast, enrichment of intracellular ascorbate is accomplished by pro-vitamin C in which its 2,3-enediol moiety is protected with phosphate ester, being thereafter enzymatically esterolyzed. Ascorbic acid-2-O-phosphate (Asc2P) gradually releases ascorbate, which is cumulatively taken up into diverse human or mammalian cells, and prevents cell injuries such as post-ischemic reperfusional injury in the liver or heart, age-dependent telomeric DNA shortening in endothelial or epithelial cells, UV-B irradiational injury in the skin and lipid peroxide-induced injury in the vascular endothelium, and tumor invasion and metastasis.

Animals↗
PubMed1999

[A recurrent case of esophageal cancer in which metastatic skin tumor disappeared after local injection of activated lymphocytes with tumor-pulsed dendritic cells].

We examined the effect of activated lymphocytes stimulated with tumor-pulsed dendritic cells (DC-K), and found that such stimulation enhanced the cytotoxity of the activated lymphocytes. Furthermore, in applying DC-K to a recurrent case of esophageal cancer, the skin tumors disappeared after local injection of DC-K. The only adverse effect of this treatment was pyrexia. Although no general effect was observed, the local effect was satisfactory. This suggests that DC-K might be useful for local treatment or postoperative adjuvant therapy.

Aged↗
PubMed1999

Antimetastatic and anti-invasive ability of phospho-ascorbyl palmitate through intracellular ascorbate enrichment and the resultant antioxidant action.

A lipophilic and auto-oxidation-resistant derivative of ascorbic acid (Asc), Asc-2-O-phosphate-6-O-palmitate (Asc2P6Plm), was shown to exert an invasion-inhibitory action as promptly as 30-40 min for 50% inhibition and 60-90 min for 80% inhibition after entering fibrosarcoma HT-1080 cells. Invasive inhibition of 95-97% was accomplished by Asc2P6Plm of doses exhibiting no cytotoxicity under the same conditions. Asc2P6Plm was dephosphorylated and esterolyzed to Asc, which enriched the intracellular Asc dose dependently in invasion-suppressed cells, contrasting with no detectable Asc in invasive cells fed without Asc2P6Plm. Intracellular dehydroAsc (DehAsc), unexpectedly, amounted to 1.02-1.65-fold as much as intracellular Asc, suggesting that invasive cells underwent oxidative stress, the repression of which resulted in both inhibition of tumor invasion and oxidative conversion of Asc to DehAsc. Correspondingly, intracellular oxidants fluorometrically detected with a redox indicator CDCFH were more abundant in invasive cells than in invasion-suppressed cells fed with Asc2P6Plm. Invasion inhibitory effects of Asc2P6Plm necessitated the extensive inhibition of the major gelatinases MMP-9 and MMP-2, as shown by zymography and Western blots, but did not necessitate direct expression of the metastasis suppressor gene nm23, taking as long as 6-18 h in contrast to a prompt action of Asc2P6Plm. Antimetastatic effects on melanoma B16BL6 cells were given dose dependently by intravenous administration or pretreatment with Asc2P6Plm. Thus, Asc2P6Plm is anticipated as an antimetastatic agent via the potent antioxidant activity.

Animals↗
PubMed1998

Surgical treatment for carcinoma of the thoracic esophagus with major involvement in the neck or upper mediastinum.

BACKGROUND AND OBJECTIVES: In carcinoma of the thoracic esophagus, most surgeons consider that esophagectomy is contraindicated in patients with clinical evidence of major extraesophageal involvement in the lower neck or peritracheal regions. However, metastases to these regions are commonly found even in early phases of carcinoma invasion. With recent progress in preoperative assessment, operative technique and adjuvant therapy, esophagectomy could possibly benefit appropriately selected patients. METHODS: We retrospectively analyzed results in 42 patients who had major involvement in the neck or upper mediastinum and who underwent esophagectomy with systematic lymph node dissection. We operated upon patients unless lesions were assessed as definitely unresectable. Preoperatively, 32 had enlarged peritracheal nodes greater than 15 mm in diameter on computed tomography, 18 had hard unmobile tumors in the lower neck, 9 had recurrent laryngeal nerve palsy, and 10 had findings suggestive of tracheal invasion. Preoperative radiotherapy and/or chemotherapy was given to 32 low-risk patients. RESULTS: The hospital mortality rate was 4%. Bowel reconstruction was completed in all cases. No macroscopically recognizable lesion remained after operation in 35 patients. Eight patients were alive 5 years after esophagectomy, including 2 who had had tracheal invasion and 1 with recurrent nerve palsy. The cumulative 5-year survival was 38%. CONCLUSIONS: Evidence of major involvement of the neck and/or upper mediastinum does not always contraindicate resection. Aggressive esophagectomy combined with perioperative adjuvant therapy yielded acceptable palliation and occasional cure in cases with technically resectable lesions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

The rotational angle in osteoarthritic knees.

The angle of rotation of the knee joint during weight-bearing in osteoarthritic knees has not been fully determined. The authors aimed to examine the nature and extent of rotation during weight-bearing by means of ultrasonic investigation. There was a highly significant correlation between the rotational angle measured by ultrasound and that determined by CT. The dynamic rotatory movement during weight-bearing was measured in 107 osteoarthritic and 40 control knees. At 20 degrees of flexion the internal rotation of the early grade I osteoarthritic knees (-1.6 degrees) was significantly less than that of the control knees (-4.8 degrees, P = 0.004). This abnormality was the initial pathological rotational change in osteoarthritis of the knee joint. The external rotation at maximal extension and the rotation of the screw-home movement proportionately decreased with progression of medial compartment osteoarthritis. By virtue of these observations we have clarified the dynamic rotatory movement in osteoarthritic knees during weight-bearing.

Adult↗
PubMed1998

Age-dependent telomere shortening is slowed down by enrichment of intracellular vitamin C via suppression of oxidative stress.

Telomeres in eukaryotic somatic cells are destined to the age-dependent shortening, which has not been demonstrated to correlate to direct lesion of telomeric DNA by reactive oxygen intermediates (ROI); still less explicable is the inhibitory effect of ROI-scavenging on telomere shortening. Here, we succeeded in artificial slowdown of age-dependent telomere shortening to 52-62% of the untreated control, in human vascular endothelial cells, by addition of the oxidation-resistant type of ascorbic acid (Asc), Asc-2-O-phosphate (Asc2P), which concurrently achieved both extension of cellular life-span and prevention of cell size enlargement indicative of cellular senescence. The results are attributable to a 3.9-fold more marked enrichment of intracellular Asc (Asc(in)) by addition of Asc2P, subsequently dephosphorylated before or during transmembrane influx, than by addition of Asc itself, and also attributed to diminution of intracellular ROI to 53% of the control level by Asc2P; telomerase activity was at a trace level and underwent an age-dependent decline, which was significantly decelerated by Asc2P. Thus, age-dependent telomere-shortening can be decelerated by suppression of intracellular oxidative stress and/or by telomerase retention, both of which are achieved by enriched Asc(in) but not by extracellular Asc overwhelmingly more abundant than Asc(in).

Ascorbic Acid↗
PubMed1998

Cervicothoracic approach for total mesoesophageal dissection in cancer of the thoracic esophagus.

BACKGROUND: The clinical significance of lymph node involvement along the recurrent laryngeal nerves in cancer of the thoracic esophagus is still controversial. Although these lymph nodes are anatomically located in a well-defined compartment (proximal mesoesophagus), appropriate procedures for dissecting them are not well established. STUDY DESIGN: We retrospectively investigated clinical results over the past 10 years in 276 patients who underwent systematic dissection of cervical, mediastinal, and upper abdominal lymph nodes. We routinely performed the cervical procedure before thoracotomy for total dissection of the proximal mesoesophagus and to minimize the operative risk. RESULTS: All macroscopically recognizable lesions were resected in 94% of the patients. The hospital mortality rate was 2.5%. Recurrent nerve palsy developed in 59 patients, but it was successfully managed without prolonged hoarseness in 50 of them. The recurrent nerve node group was most frequently involved (frequency of 25% in superficial cancer, 57% in non-superficial cancer). Supradiaphragmatic lymph node involvement was limited to the recurrent nerve nodes in 25% of the patients with positive supradiaphragmatic node. The 5-year survival rate in patients with positive recurrent nerve nodes was 34%. CONCLUSIONS: Dissection of the recurrent nerve lymph nodes is essential for curative esophagectomy even in the early phase of cancer invasion. Our cervicothoracic approach for total dissection of the proximal mesoesophagus yielded acceptable outcomes.

Carcinoma, Squamous Cell↗
PubMed1998

[Clinical evaluation of intermittent hepatic arterial infusion therapy for metastatic liver tumor of gastric and colorectal cancer].

Eleven patients with liver metastasis from gastric cancer were treated by intermittent arterial infusion using OK-432 and recombinant IL-2 in combination with anticancer drugs. The direct effects for liver metastasis were PR 3 (response rate 30%), MR 2, NC 3, PD 1 and NE 1. Papillary adenocarcinoma showed a highly effective rate. The mean survival period was 326 days and the 50% survival period was 318 days. Out of 4 patients who underwent surgical resection for metastatic liver tumor, one showed recurrence, and the other is now healthy without any sign of recurrence for 8 years after the operation. In 7 patients with liver metastasis from colorectal cancer, intermittent arterial infusion therapy using Leucovorin, CDDP and 5-FU was performed. The direct effects were CR 2, PR 1, MR 1, PD 2, NE 1; the mean survival period was 478 days, and the 50% survival period 556 days. Out of 8 patients who underwent liver resection for metastasis, all patients remained alive for 687 mean survival days without liver recurrence. No severe side effects were noted in either therapy.

Adenocarcinoma, Papillary↗
PubMed1997

Moderately controlled transport of ascorbate into aortic endothelial cells against slowdown of the cell cycle, decreasing of the concentration or increasing of coexistent glucose as compared with dehydroascorbate.

Uptake of L-[1-(14)C]ascorbic acid (Asc) of 12.5-200 microM for 1 h into bovine aortic endothelial BAE-2 cells grown to confluence was as low as 43-64% (per cell) of uptake into the cells grown to nearly one-fourth confluence. [14C]Asc undergoing transmembrane uptake was concentrated and accumulated in the cell less efficiently ([Asc]in/ex = 8-13) at confluence than at subconfluence ([Asc]in/ex = 15-24). The declined Asc uptake at confluence is attributable to slowdown of the cell cycle, because a similar decrease in [Asc]in/ex was shown by subconfluent cells precultured in serum-insufficient medium, resulting in an increase in G1 phase and concurrent decreases in S and G2 + M phase distributions as determined by flow cytometry. [1-(14)C]Dehydroascorbic acid (DehAsc) was taken up and accumulated as Asc, after metabolic reduction, without detectable DehAsc. The [Asc]in/ex values for DehAsc at confluence were as low as 15-69% of those at subconfluence in contrast to the values as retentive as 62-75% for Asc, suggesting the moderate control of Asc uptake against slowdown of the cell cycle. At either confluence or subconfluence, dose-dependence for DehAsc uptake was more marked than for Asc uptake as shown by an uphill slope in a curve of doses versus [Asc]in/ex for DehAsc in contrast to a downhill slope for Asc, suggesting the moderate control for Asc uptake against fluctuation of the dose. Increasing of coexistent glucose of 5 mM to 20-40 mM, plasma concentrations in diabetic patients, declined DehAsc uptake to 46-48%, which was less moderately controlled than Asc uptake retained to 59-73%. Asc uptake did not compete with DehAsc uptake, suggesting different transporter proteins for Asc and DehAsc. Thus, Asc uptake into the aortic endothelial cells is more moderately controlled against slowdown of the cell cycle, decreasing of the extracellular concentrations or increasing of coexistent glucose than DehAsc uptake, suggesting a homeostatic advantage of Asc over DehAsc in terms of retention of intracellular Asc contents within a definite range.

Animals↗
PubMed1997

Further analysis of Del (D-elute) using polymerase chain reaction (PCR) with RHD gene-specific primers.

Del (D-elute) in the Rh blood group system is a variant with very weak D antigen and no agglutination is found by the indirect antiglobulin test. This variant is characterized by the presence of anti-D eluate obtained after an adsorption-elution test using anti-D antibodies. We studied here the molecular genetic status of Del by using polymerase chain reaction with sequence-specific primers (PCR-SSP). We screened 306 serologically apparent D-negative Japanese donors comprising 102 Del types for exons 7, 4 and 10 of the RHD gene. No PCR product was found in all 204 non-Del samples from the D-seronegative donors. However, PCR products were found in all 102 Del samples and all 70 D-seropositive samples tested by the three PCR methods for exons 7, 4 and 10 analysis. Del was found with CCee, CcEe and Ccee, but not with CCEe, CcEE, ccEE, ccEe or ccee phenotype. The incidences of Del in the samples with the serological phenotypes CCee, CcEe and Ccee were 80.0% (4/5), 68.2% (45/66) and 61.6% (53/86), respectively. The results provide evidence that Del samples have exons 4, 7 and 10 of an RHD gene present in some form. This is consistent with the evidence that D antigen is present on the cells although only detected by antibody adsorption and elution. The PCR-SSP method in the present study is useful to confirm Del among serologically apparent D-negative samples.

Asian People↗
PubMed1997

DBT: a partial D phenotype associated with the low-incidence antigen Rh32.

Eight probands are described with a D phenotype in which a partial D antigen is associated with Rh32 antigen; three of these probands were investigated because of the anti-D in their serum. The partial D lacks epD1-epD5 and epD9 and some epD6/7 and only expresses epD8 and other parts of epD6/7. The strength of the partial D antigen varies between unrelated DBT individuals. The Rh32 antigen of the DBT cells is weaker than that of D(C)(e) cells. Tests on DBT, DFR and R0Har cells with anti-epD6/7 split these monoclonal anti-D into eight patterns of reaction. A new pattern of reactions was observed, presaging a new epitope, but this was not numbered.

Antibodies, Monoclonal↗