Biomedical subjects

N Nagao

Publications and source records attributed to N Nagao.

At least 19 recordsLinked to original sources

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↗

PubMed1997

Enhanced protection against peroxidation-induced mortality of aortic endothelial cells by ascorbic acid-2-O-phosphate abundantly accumulated in the cell as the dephosphorylated form.

Bovine aortic endothelial BAE-2 cells exposed to the peroxidizing agent, tert-butylhydroperoxide (t-BuOOH) or 2,4-nonadienal (NDE), suffered from disruption of cell membrane integrity and from reduction of mitochondrial dehydrogenase activity as assessed by fluorometry using ethidium homodimer and photometry using WST-1, respectively. The cells were protected from t-BuOOH-induced injury more markedly by L-ascorbic acid-2-O-phosphate (Asc2P) stably masked at the 2,3-enediol moiety, which is responsible for the antioxidant ability of L-ascorbic acid (Asc), than by Asc itself. In contrast, NDE-induced membrane disruption but not mitochondrial dysfunction was prevented by Asc2P, whereas Asc exhibited no prevention against both types of injury. The amount of intracellular Asc was 7.2- to 9.0-fold larger in Asc2P-administered BAE-2 cells, where the intact from Asc2P was not detected, than in Asc-administered cells as assessed by HPLC of cell extract with detection by coulometric ECD and UV. During transmembrane influx into the cell, Asc2P was concentrated as highly as 70- to 90-fold relative to the extracellular Asc2P concentration, whereas Asc was 8- to 13-fold concentrated as estimated based on an intracellular water content of 0.59 pL/cell determined by [14C]PEG/gas chromatography. Thus, Asc2P but not Asc is highly concentrated in the aqueous phase of the cell after prompt dephosphorylation, and may thereby render the cell more resistant to t-BuOOH-peroxidation assumedly via scavenging of intracellular reactive oxygen species than to peroxidation with the less hydrophilic agent NDE.

Animals↗

PubMed1997

[Mediastinal amelanotic melanoma presenting as superior vena cava syndrome].

A 60-year-old man was admitted to the hospital with anterior chest discomfort and superior vena cava syndrome. A chest X-ray film revealed a right upper mediastinal mass. A needle biopsy was done. Anaplastic tumor cells was found after HE staining. No melanin was found and the origin of the tumor cells could not be determined. Radiation and chemotherapy caused the tumor to shrink markedly. Because the tumor had invaded the superior vena cava, only reduction surgery could be done. The patient died 6 months after admission. Amelanotic malignant melanoma was diagnosed after immunohistochemical study of the resected specimen. Mediastinal malignant melanoma has been reported very infrequently and to our knowledge this is the first report of mediastinal amelanotic malignant melanoma.

Humans↗

PubMed1997

Cytotoxicity to tumors by alpha, beta-dihydric long-chain fatty alcohols isolated from esterolysates of uncytotoxic sheep cutaneous wax: the dependence on the molecular hydrophobicity balance of N- or iso-alkyl moiety bulkiness and two hydroxyl groups.

Wool fatty alcohols (WF-Alc; C10-C33), separated by esterolysis of wool grease secreted from sheep sebaceous gland, inhibited growth of mouse Ehrlich ascites carcinoma (EAC) cells in contrast to no inhibition by unesterolysed wool grease. WF-Alc was fractionated by molecular distillation and subsequent octadecylsilica (ODS) gel liquid chromatography, showing that most of the growth-inhibitory activity was found in the most hydrophilic fraction with the lowest boiling-point (MW 200-300; C12-C20), ODS-HPLC of the fraction showed that most of the activity resided in two homogeneous fractions identified by GC-MS and 13C-/1H-NMR as alpha, beta-dihydric saturated fatty alcohols such as 1,2-hexadecanediol (n-C16(OH)2) and 16-methyl-1,2-heptadecanediol (iso-C18(OH)2), respectively. EAC cells implanted into mice were inhibited markedly by n-C16(OH)2 possessing a cytolysing ability and slightly by iso-C18(OH)2, but hardly by other alkyl-alpha, beta-diols (C12-C24) contained in WF-Alc. Thus, the antitumor activity of WF-Alc was exhibited only after saponification of uncytotoxic wool grease, showing necessity of unesterified hydroxyl groups, and was dependent upon the molecular hydrophobicity balance attributed to both hydroxyl groups and n- or iso-alkyl moiety bulkiness specified out of diverse species of fatty alcohols contained in WF-Alc.

Animals↗

PubMed1996

Promotive action of acylated ascorbate on cellular DNA synthesis and growth at low doses in contrast to inhibitory action at high doses or upon combination with hyperthermia.

Effects of 6-O-palmitoyl ascorbate (ascorbate) developed to increase the antitumour activity of ascorbic acid on DNA synthesis and proliferation of Ehrlich ascites tumour cells were investigated. Treatment of the cells with the acylated ascorbate at 25-50 microM for 1 h resulted in no effect on DNA synthesis, assayed by pulse incorporation of [3H]thymidine after a culture period of 20 h, but led to 49%-87% enhanced DNA synthesis after 4 days, suggesting that long-term culture is required for promotion by ascorbate to occur. At a dose as high as 75 microM acylated ascorbate, however, cellular DNA synthesis was 64% inhibited after 20 h and 99% after 4 days. The results suggest that acylated ascorbate exhibits a dual action on DNA synthesis: promotion at low doses and inhibition at high doses, both of which are potentiated in a time-dependent manner. In contrast to the above-mentioned results at 37 degrees C, acylated ascorbate at 25-75 microM inhibited but did not promote DNA synthesis at 42 degrees C whatever the culture period. Similar results were exhibited when proliferation of cells cultured for a long period was investigated. At 37 degrees C, 50 microM acylated ascorbate increased the number of the cells to 3.6 times the control values after 8 days and to 1.9 times after 11 days; in contrast, a 75-microM dose decreased the cell number considerably. Combination with hyperthermia (42 degrees C) suppressed the increase and cell growth was completely inhibited at 75 microM.

Acylation↗

PubMed1996

Rapid detection of the cisAB allele consisting of a chimera of normal A and B alleles by PCR-RFLPs.

DNA samples were analysed from Japanese individuals with the very rare ABO variant phenotype, cisAB (A2B3), which is characterized by the apparent inheritance of both A and B genes on one chromosome. The nature of the bases present at nucleotide positions (nps) 261, 526, 703, 796 and 803 is important for the specificity of the alleles at the ABO locus and the DNA from the cis AB donors was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine which nucleotides are present at these positions. The results indicated that the cisAB allele had the AAAB-structure, which was a chimera of normal A and B alleles, when the expression 'AAAA' and 'BBBB' indicated the nucleotides of normal A (C, G, C and G) and B (G, A, A and C) genes at nps 526, 703, 796 and 803, respectively. The AAAB allele was found in all 27 individuals (17 families) with the cisAB including three phenotypes A2B3, A1B3 and A2B and no other chimeric gene was found. The causative gene of cisAB was the AAAB allele, and the A and B alleles were not on one chromosome. The cisAB allele appeared to be a product of the normal A allele due to a point mutation at nucleotide position 803, from G to C. The AAAB allele is thought to be normally transcribed and translated to produce an unusual transferase polypeptide, which has weak A- and weaker B-specific activity. PCR-RFLP is a rapid and useful means of detecting the cisAB allele (the AAAB allele) without a family study, even when they have A1B3 and A2B phenotypes, because trans-type A1B3 and A2B samples have obviously different PCR-RFLP profiles.

ABO Blood-Group System↗

PubMed1996

Genotype frequencies of the human platelet antigen, Ca/Tu, in Japanese, determined by a PCR-RFLP method.

Recently, the polymorphism of a new human platelet antigen, Ca/Tu, was shown to be derived from a G-A nucleotide substitution at base 1564 of GPIIIa cDNA, which leads to a single amino acid difference, Arg/Gln at amino acid 489 of GPIIIa. We developed a PCR-RFLP method to determine the genotypes of Ca/Tu and their frequencies in a Japanese population. Fifteen Ca/Tua donors comprising 1 Ca/Tu(a/a) homozygous donor and 14 Ca/Tu(a/b) heterozygous donors were found among the 314 random donors analyzed. The frequencies of Ca/Tu genes were 0.025 (Ca/Tua) and 0.975 (Ca/Tu(b)). The present study showed that the frequency of Ca/Tua individuals in the Japanese (15/314) was approximately 7-fold higher than in the Finnish population (1/150) previously reported by Kekomäki et al. Therefore, attention must be given to the involvement of the Ca/Tu alloantigen in neonatal alloimmune thrombocytopenia and the refractoriness of platelet transfusion.

Antigens, Human Platelet↗

PubMed1996

[Follow-up of HIV carriers by a laboratory method. I: Virus isolation is useful for prognostication of the onset of symptoms].

We followed 54 HIV-1 carriers (44 asymptomatic carriers and 10 AIDS patients) by virus isolation and immunological examination and evaluated their usefulness for prognostication of the onset of symptoms. From 37 carriers (27 asymptomatic carriers and 10 symptomatic), 132 HIV-1 strains were isolated; the virus isolation rate was 60% in the asymptomatic carriers (AC) but 100% in the symptomatic. In the AC, the isolation rate was 54.5% in the group showing stable in the CD4+ level but 95.5% in the group showing a decrease in the CD4+ level. With progression of the disease, the culture time required for virus isolation was shortened, and the percentage of isolates showing infectivity to the T-cell line (MT-4 cells) increased. These findings suggest that the virus in the body is changed with progression of the disease to that showing rapid replication, T-cell tropic, and high pathogenicity. Indeed, progression of the disease was observed in all carriers in whom a highly pathogenic virus was detected; some developed the disease within 1 year, some showed temporary recovery in the CD4+ level after AZT administration followed by progression to ARC, and others showed a rapid decrease in the CD4+ level. In contrast, in carriers with only slightly pathogenic virus, the CD4+ level was maintained for a long period. These results suggest that the detection of a highly pathogenic virus is one of the most reliable marker for the prognostication of the onset of the disease. The detection of HIV-1 antigen in the plasma and a decrease in the gag antibody were also associated with the progression of the disease. However, the reliability of these markers seems to be lower than that of virus isolation.

Acquired Immunodeficiency Syndrome↗

PubMed1996

A single nucleotide insertion in codon 317 of the CD36 gene leads to CD36 deficiency.

CD36 is a multifunctional integral-membrane glycoprotein that acts as a receptor for thrombospondin, collagen, long-chain fatty acids, and oxidized LDL. Platelet CD36 deficiency can be divided into two groups. In type I, neither platelets nor monocytes/macrophages express CD36; in type II, monocytes/macrophages express CD36 but platelets do not. Two known mutations cause CD36 deficiency, ie, a 478C-->T substitution in codon 90 (proline90-->serine) and a dinucleotide deletion at nucleotide 539 in codon 110. In this study we investigated a type I Japanese subject (A.T.) and identified a new mutation, a single nucleotide insertion at nucleotide 1159 in codon 317. This mutation leads to a frameshift and the appearance of a premature stop codon. CD36 gene analysis indicated that A.T. was a compound heterozygote for a dinucleotide deletion at nucleotide 539 and the single nucleotide insertion at nucleotide 1159. RNase protection studies suggested that the new mutation as well as the dinucleotide deletion led to a marked reduction in the level of CD36 mRNA in her macrophages. However, the new mutation could be detected in macrophage but not platelet CD36 mRNA. These data suggest that the allele having the single nucleotide insertion in this subject has an additional abnormality that results in the absence of the mutated CD36 mRNA in platelets.

Base Sequence↗

PubMed1996

Changes of expression of complement 3bi receptors on granulocytes after physical exercise in rats.

OBJECTIVE: The purpose of this study was to examine the effects of physical exercise on the expression of clusters of differentiation (CD)11b, CD18 and CD 54 on granulocytes and complement 3bi (C3bi)-dependent functions in rats. EXPERIMENTAL DESIGN: The rats were separated into two groups: the control group (n = 21) and the training group (n = 14). The rats in the training group were subjected to a program that consisted of swimming 6 days in a week for 7 weeks. MEASURES: The phagocytic and hydrogen peroxide (H2O2) generating activities and the expression of receptors on granulocytes were measured using flow cytometric techniques. RESULTS: The acute swimming and the 7 weeks of swim training caused high C3bi-dependent phagocytic activity of granulocytes. Swim training led to an increase of H2O2 generating activity together with C3bi-dependent phagocytosis both immediately after and 24 hrs after the 120 min swimming. The 24 hrs recovery from the 120 min swimming in trained and untrained rats caused an increase of H2O2 generating activity of granulocytes. In the training group, an increase in this activity could be observed immediately after the 120 min swimming exercise. The upregulation of the CI1b on granulocytes was induced by the 120 min of swimming regardless of swim training. CONCLUSIONS: These results suggest that the increase of C3bi receptor-dependent phagocytosis and H2O2 generating activities induced by the physical exercise might depend on the upregulation of the CD11b that is the component of C3bi receptor.

Animals↗

PubMed1995

Simultaneous DNA typing of human platelet antigens 2, 3 and 4 by an allele-specific PCR method.

We developed an allele-specific polymerase chain reaction (ASPCR) method using originally designed primers to determine the genotype of the human platelet antigens (HPAs) 2, 3 and 4 in parallel. The results were compared with those obtained by PCR restriction fragment length polymorphism and the mixed passive hemagglutination test. Seventy-three individuals were tested and the ASPCR results were in good agreement with those determined by the other two methods. This method enables the genotyping of HPA-2, -3 and -4 in parallel without the use of platelets, platelet-specific alloantibodies or restriction enzymes.

Alleles↗