Biomedical subjects

T Akama

Publications and source records attributed to T Akama.

At least 19 recordsLinked to original sources

PubMed2003

Effects of 12 months of exercise training on salivary secretory IgA levels in elderly subjects.

BACKGROUND: The immune system declines in efficiency with advancing age, making the elderly less resistant to pathogenic microorganisms. Upper respiratory tract infection (URTI) is a common illness. Recent studies have shown that suppression of secretory immunoglobulin A (SIgA) is associated with increased incidence of URTI. OBJECTIVE: To assess the effect of exercise on salivary SIgA in elderly subjects. METHODS: Forty five elderly subjects (18 men, 27 women; mean (SD) age 64.9 (8.4) years) performed both 60 minute resistance and 60 minute moderate endurance training a week for 12 months. Saliva samples were obtained before training, and at four and 12 months during the training period. Salivary SIgA concentrations were measured by enzyme linked immunosorbent assay, and the SIgA secretion rate was calculated. RESULTS: SIgA concentrations before training, and at four and 12 months during training were 24.7 (14.4), 27.2 (14.2), and 33.8 (18.5) micro g/ml respectively. SIgA secretion rates were 29.5 (26.0), 33.8 (27.2) and 46.5 (35.1) micro g/min respectively. The results indicate that both the concentration and secretion rate of SIgA significantly (p<0.01) increased during 12 months of exercise in these elderly subjects. CONCLUSION: Regular moderate exercise seems to enhance mucosal immune function in elderly subjects.

Aged↗

PubMed2001

Antiprothrombin autoantibodies in severe preeclampsia and abortion.

PURPOSE: We examined the levels of autoantibodies against prethrombin-1 and fragment-1 in pregnant women to determine the type of autoantibodies that were associated with severe preeclampsia or spontaneous abortion. SUBJECTS AND METHODS: We measured autoantibodies bound to prothrombin, prethrombin-1, and fragment-1 by using an enzyme-linked immunosorbent assay (ELISA) in 12 healthy nonpregnant women, 36 women with normal pregnancies, 28 pregnant women with severe preeclampsia, and 19 pregnant women who subsequently had spontaneous abortion. RESULTS: Plasma samples in 10 (36%) of the 28 women with severe preeclampsia and 11 (58%) of the 19 women with spontaneous abortion were positive for antiprothrombin antibodies as compared with 3 (9%) of the 36 women with normal pregancies. All 11 of the positive samples from women who had spontaneous abortions were positive for antiprethrombin-1 antibody, but only 1 was positive for antifragment-1 antibody. The mean (+/- SD) titer of antiprethrombin-1 antibodies in patients with spontaneous abortion (36 +/- 9 U) was higher than that in women with normal pregnancies (10 +/- 4 U; P < 0.01). Antiprethrombin-1 antibody was detected in only 2 women with severe preeclampsia, whereas all 10 women with antiprethrombin antibodies were positive for antifragment-1 antibody. The antifragment-1 antibody titer in patients with severe preeclampsia (49 +/- 15 U) was higher than in women with normal pregnancies (13 +/- 6 U, P < 0.01). CONCLUSIONS: There is a strong and specific association between various types of antiprothrombin antibodies with severe preeclampsia and spontaneous abortion.

Abortion, Spontaneous↗

PubMed2000

A genetic linkage map of the MSM Japanese wild mouse strain with restriction landmark genomic scanning (RLGS).

A high-resolution genetic map of the Mus musculus molossinus (MSM) Japanese wild mouse strain was constructed with restriction landmark genomic scanning (RLGS) and compared with that of the laboratory strain C3H. MSM is phylogenetically 1 million years apart from common laboratory mouse strains and is distinctly resistant to chemical carcinogenesis. Since it exhibits frequent genetic polymorphisms with laboratory mice but can still be easily crossed with laboratory strains, hybrids between MSM and carcinogen-sensitive laboratory mouse strains provide excellent materials for analysis of modifier genes and genetic changes during carcinogenesis. We have generated MSM backcross progeny with the C3H strain, which is extremely sensitive to hepatocarcinogenesis, to construct the present map. RLGS profiles with two combinations of restriction enzymes (NotI-PvuII-PstI, NotI-PstI-PvuII) yielded more than 2000 spots each. The polymorphism rate was about 39.2%, and of a total of 1732 polymorphic spot loci identified, 1371 could be assigned to specific chromosomes by comparison with 79 microsatellite marker loci. Thus, 1450 loci, on all chromosomes except for Y, effectively mapped 90% of the genome (1431.7 cM length). Although some spots might be derived from the same NotI site, each NotI site potentially generating two fragments, the presence of at least 515 loci groups with different progeny distribution patterns dispersed through the genome with an average spacing of 3 cM, means that this genetic map should be useful for analysis of various biological phenomena, including carcinogenesis and ontogenesis, at the gene level.

Animals↗

PubMed2000

Effect of brief maximal exercise on circulating levels of interleukin-12.

Interleukin-12 (IL-12) is a cytokine that was originally identified as natural killer cell stimulatory factor. It induces the activity of T-helper 1 (Th1) cells and exhibits strong anti-tumor activity. In this study, we studied the effects of brief anaerobic maximal exercise on circulating levels of IL-12. Six healthy males [mean (SD) 25.2 (2.6) years] performed a modified Wingate test exercise (resistance 0.075 kg/kg of body mass). The exercise consisted of five bouts of maximal cycling for 10 s, with rest intervals of 50 s between them. Blood samples were taken before, immediately after, 30 min after, 60 min after and 120 min after the exercise. Plasma concentrations of IL-12 were measured using an enzyme-linked immunosorbent assay. Data were corrected for hemoglobin and hematocrit measurements. Plasma concentrations of IL-12 averaged [mean (SD)] 234.2 (40.9) pg/ml before, 305.2 (62.1) pg/ml immediately after, 202.8 (24.2) pg/ml 30 min after, 239.7 (35.1) pg/ml 60 min after, and 199.6 (49.2) pg/ml 120 min after the exercise. We showed that plasma concentrations of IL-12 increased significantly immediately after brief anaerobic maximal cycle ergometer exercise (P < 0.01).

Adult↗

PubMed2000

Palmar fasciitis and polyarthritis associated with gastric carcinoma: complete resolution after total gastrectomy.

Palmar fasciitis and polyarthritis (PFA) is a rare paraneoplastic rheumatic syndrome characterized by flexion contractures of both hands and thickening of palmar fascia. Several reports have suggested that this syndrome is a tumor-associated autoimmune disorder. We report a 44-year-old Japanese man who presented with flexion contractures of both hands associated with thickening of palmar fascia and polyarthritis. These clinical pictures were suggestive of PFA associated with occult neoplasm. Upper gastrointestinal endoscopic examination revealed advanced gastric cancer. Resection of the cancer resulted in a gradual resolution of palmar fasciitis and polyarthritis. This clinical course suggests an underlying tumor-related immunologic process in this syndrome.

Adenocarcinoma↗

PubMed2000

The relationship between serum immunoglobulin levels and pulmonary involvement in systemic sclerosis.

OBJECTIVE: To examine the relationship between serum immunoglobulin (Ig) levels and pulmonary function in patients with systemic sclerosis (SSc). METHODS: Twenty-four patients with SSc who had at least 2 sets of pulmonary function tests (PFT) at intervals of more than one year were eligible. Multiple linear regression models were constructed for prediction of the annualized rates of change of forced vital capacity (FVC), carbon monoxide diffusing capacity (DL(CO)), and DL(CO) per unit alveolar volume (K(CO)). RESULTS: The rates of change of FVC and K(CO) correlated with the annualized rate of change of IgG (p < 0.001 and p = 0.005, respectively), and the rate of change of DL(CO) correlated with the serum IgM level at the first PFT (p = 0.020) and with the annualized rate of change of IgG (p = 0.007). CONCLUSION: The rates of change of serum Ig levels are associated with those of pulmonary function in SSc. Use of this model may assist investigation of pulmonary involvement.

Adult↗

PubMed1999

Complete recovery from intractable bulimia nervosa by the surgical cure of primary hyperparathyroidism.

We document here the first case of bulimia nervosa associated with primary hyperparathyroidism. The binge eating and self-induced vomiting that occurred for more than 10 years disappeared completely after the surgical cure of primary hyperparathyroidism. Depressive and anxiety symptoms also improved dramatically. The possible influence of derangement in calcium metabolism on the neurobiochemical mechanism of bulimia nervosa is discussed.

Adult↗

PubMed1999

Relationship between clinical features and binding domains of anti-prothrombin autoantibodies in patients with systemic lupus erythematosus and antiphospholipid syndrome.

Autoantibodies against prothrombin, including lupus anticoagulant antibodies (LAC), have been identified in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). To identify the epitopes of LAC in patients with SLE and APS, we analyzed B cell epitopes of anti-prothrombin Abs. Prothrombin was purified from fresh plasma samples from healthy subjects, and fragmented by thrombin. Two fragments (prethrombin-1, 50 kDa, and fragment-1, 22 kDa) were separated and used for further experiments. The two fragments were coated on irradiated plate and the binding activities of sera from 13 patients with anti-prothrombin Abs (SLE, 7; APS, 4; SLE+APS, 2) were determined by using ELISA. The assay was conducted under the following conditions: use of irradiated plates, and TBS containing Tween-20. We detected two types of anti-prothrombin Abs. The first was anti-prethrombin-1 (n=5) while the other was Ab against fragment-1 (n=8). There were no patients with Abs that showed binding activities to both fragments. A higher proportion of patients with thrombosis were positive for anti-prethrombin-1 Abs (80%) than for anti-fragment-1 Abs (25%). Two patients with anti-prethrombin-1 Ab were positive for LAC and negative for anti-cardiolipin-beta2 glycoprotein I antibody (aCL-beta2GPI). Our results strongly support the notion that both prethrombin-1 and fragment-1 on prothrombin molecule are B cell epitopes.

Antibody Specificity↗

PubMed1999

Detergent and antigen fragility affect the ELISA for measurement of anti-prothrombin autoantibodies.

OBJECTIVE: Some investigators have reported that anti-prothrombin autoantibodies (aPT) in lupus anticoagulant positive sera were detectable by ELISA. Discrepancies in aPT ELISA were observed by some investigators. To clarify this situation, we tested the binding of aPT positive sera to purified prothrombin under various conditions. METHODS: We performed aPT ELISA under different conditions. The variables we tested were: ELISA plate (untreated or gamma irradiated polystyrene plates), buffer (phosphate buffered saline or Tris buffered saline), detergent (presence or absence of Tween-20), and antigen condition (intact or fragmented prothrombin). RESULTS: Anti-PT from patients with lupus or antiphospholipid syndrome were similarly bound to prothrombin with both buffers. Addition of Tween-20 to the buffer increased reactivity in the irradiated plate assay, but decreased reactivity in the untreated plate assay. Reactivities in 90% of lupus sera were decreased by the use of fragmented prothrombin. In contrast, the reactivity of serum from a healthy subject was remarkably increased by antigen fragmentation. CONCLUSION: The discrepant ELISA results in measurement of aPT in the various reports may have been due to the use of detergent in the buffer and condition of the prothrombin used as antigen. In our experiments the best ELISA condition for measurement of aPT was achieved using buffer with Tween-20 detergent, with prothrombin directly coated onto irradiated polystyrene plates.

Antiphospholipid Syndrome↗

PubMed1999

Dieulafoy's lesion of the esophagus as a probable complication of Takayasu's arteritis.

Dieulafoy's lesion is an abnormal submucosal artery in the gastrointestinal tract characterized by massive gastrointestinal bleeding. We describe a patient who developed Dieulafoy's lesion of the esophagus in the course of isolated pulmonary Takayasu's arteritis. Angiographic findings indicated a relationship between pulmonary arterial involvement of Takayasu's disease and Dieulafoy's lesion of the esophagus. This observation represents the first report of the association between Takayasu's arteritis and Dieulafoy's lesion of the esophagus.

Adult↗

PubMed1998

Structure-activity relationships of the 7-substituents of 5,4'-diamino-6,8,3'-trifluoroflavone, a potent antitumor agent.

Recently, we reported that 5,4'-diamino-6,8,3'-trifluoroflavone (1b) exhibits potent antitumor activity against certain types of human cancer cell lines both in vitro and in vivo. Since the antiproliferative activity of 5,4'-diaminoflavone (1a), the lead compound of 1b, was modulated by the addition of apigenin, we hypothesized that the 7-position is important for the interaction with a putative target molecule. On the basis of this hypothesis, the structure-activity relationships of the substituents at the 7-position of 1b were explored. As a result, 7-methyl (7a), 7-hydroxymethyl (7l), 7-(acyloxy)methyl (9a,c,e,g,j), and 7-aminomethyl (12f) derivatives were found to exhibit comparable or superior antitumor activity to compound 1b against MCF-7 cells both in vitro and in vivo (po administration). In particular, compounds 9e,g,j, and 12f were sufficiently water-soluble as compared with 1b which hardly solubilizes in water. A lipophilic 7-(hexanoyloxy)methyl derivative (9c) was also found to exhibit strong antitumor activity especially in vivo. Since the modes of action and the target molecule(s) are unknown, a mechanistic study will be important in the future.

Animals↗

PubMed1998

Systemic lupus erythematosus associated with primary large cell carcinoma of the lung.

The association between systemic lupus erythematosus (SLE) and malignancy has been controversial in the literature. We report a case of lung cancer in a 50-year-old woman with a 4-year history of SLE. She underwent surgery at a pathological stage of T2N2M0, but she eventually died of rapid recurrence of the cancer in the abdomen resulting in massive haemorrhage from the inferior vena cava (IVC). Immunological disorders related to SLE are thought to contribute to rapid progression of the malignancy.

Abdominal Neoplasms↗

PubMed1998

Enhanced interleukin 6 production by cultured fibroblasts from patients with systemic sclerosis in response to platelet derived growth factor.

OBJECTIVE: The pathophysiology of systemic sclerosis (SSc) is poorly understood, but recent studies indicate the involvement of cytokines in the functional changes of SSc fibroblasts. We investigated interleukin 6 (IL-6) production by dermal fibroblasts from patients with SSc. METHODS: Fibroblast cultures were established from affected skin of patients with SSc and from skin of healthy controls. IL-6 in supernatants from cultured fibroblasts was measured using a specific IL-6 ELISA. RESULTS: SSc fibroblasts, starved in serum-free medium, produced only a small amount of IL-6. However, IL-6 production by SSc fibroblasts dramatically increased when the cells were cultured in serum-containing medium. Human whole blood serum was more effective than human platelet-poor plasma derived serum in the enhancement of IL-6 production by SSc fibroblasts. Platelet derived growth factor (PDGF)-AA and PDGF-BB, a major growth factor in serum, induced significant IL-6 production by SSc fibroblasts. In contrast, in normal fibroblasts, much less response to PDGF-BB and almost no response to PDGF-AA were observed. Expression of PDGF receptors on SSc fibroblasts was not significantly different from normal fibroblasts. However, IL-1 receptor antagonist (IL-1ra), when added in the medium, significantly inhibited the PDGF-induced IL-6 production by SSc fibroblasts. CONCLUSION: PDGF stimulates IL-6 production by SSc fibroblasts. The enhanced IL-6 production in response to PDGF is due in part to autocrine IL-1 of SSc fibroblasts. These abnormalities of fibroblasts may play an important role in the inflammatory and immunological processes of SSc.

Adult↗

PubMed1997

Design and synthesis of potent antitumor 5,4'-diaminoflavone derivatives based on metabolic considerations.

Recently, we reported that 5,4'-diaminoflavone (1) exhibits potent and specific growth-inhibitory activity against the estrogen receptor (ER)-positive human breast cancer cell line MCF-7. However, when compound 1 was incubated with S-9 mix, its metabolites were observed. Moreover, addition of S-9 mix to the medium caused the drastic decrease in activity of compound 1. Since the 6-, 8-, and 3'-positions were considered to be metabolized oxidatively in vivo from MO calculations, a series of 5,4'-diaminoflavone derivatives substituted at such putative metabolic positions with various functional groups were synthesized aiming at the metabolically stable derivatives. Among them, 5,4'-diamino-6,8,3'-trifluoroflavone (14d) exhibited strong growth-inhibitory activity against MCF-7 cells even in the presence of S-9 mix. Moreover, orally administered compound 14d completely suppressed the growth of MCF-7 inoculated into nude mice, and the effect was more potent than that of compound 1. In addition to ER-positive breast cancer cells, compound 14d exhibited growth-inhibitory activity against a panel of human cancer cell lines including a part of ER-negative breast, endometrial, ovarian, and liver cancers. From these results, fluorine introduction to the putative metabolic positions of compound 1 was elucidated to be effective in the enhancement of the in vivo antitumor activity, probably due to the block of the metabolic deactivation.

Animals↗

PubMed1996

Novel 5-aminoflavone derivatives as specific antitumor agents in breast cancer.

In the course of our search for new antitumor agents in breast cancer, novel amino-substituted flavone derivatives were synthesized and examined for antitumor activities. Among them, 5,4'-diaminoflavone and some of its congeners showed remarkable antiproliferative activity against the estrogen receptor (ER)-positive and estrogen-responsive human breast cancer cell line MCF-7. The activity was observed irrespective of the presence or absence of estrogen. The 5-aminoflavone derivatives (5-AFs) are not classical anti-estrogens because they did not compete with [3H]estradiol to bind the estrogen receptor. Moreover, 5-AFs showed antitumor activity highly selective to the ER-positive breast cancer cell line, and they showed no effects against the ER-negative human cancer cell lines HeLa S3, WiDr, and MDA-MB-453. Although the mechanism of their selective antitumor activity to ER-positive breast cancer cells is unclear, 5-AFs are expected to be a new type of antitumor agents in breast cancer.

Antineoplastic Agents↗

PubMed1996

Nitric oxide (NO)-releasing pathway of FK409 in the presence of sulfhydryl-bearing compounds.

PURPOSE: We have recently reported that degradation of FK409 with generation of NO is spontaneous and is accelerated in the presence of sulfhydryl-bearing compounds, such as L-cysteine (Cys) and glutathione (GSH). The purpose of the present study is to investigate the NO-releasing pathway of FK409 in the presence of sulfhydryl-bearing compounds. METHODS: The degradation process of FK409 in the presence of Cys or GSH was investigated by means of 1H-nuclear magnetic resonance (NMR) spectroscopy and high-performance liquid chromatography (HPLC). RESULTS: The degradation of FK409 in the presence of Cys was dependent on concentration of Cys, and showed pH-dependency, accelerating with an increase in pH. The 1H-NMR spectra of FK409 with Cys suggested that time-dependent elimination of the hydrogen atom at the alpha-position of the nitro moiety (5-position) was accelerated by Cys in weakly alkaline solution. Cys and GSH were transformed readily, concomitant with FK409 degradation, to give their oxidized forms and probably S-nitrosothiols. CONCLUSION: The effect of sulfhydryl-bearing compounds on FK409 degradation is due to the acceleration of deprotonation of the hydrogen atom at the 5-position by thiolate anion as well as hydroxyl ion. Sulfhydryl-bearing compounds reacted with the released NO resulting in formation of disulfides via intermediate S-nitrosothiols.

Chromatography, High Pressure Liquid↗

PubMed1996

Predicting infection in hospitalized patients with systemic lupus erythematosus.

To identify the risk factors for infection and to develop a model for the prediction of infection in hospitalized patients with active systemic lupus erythematosus (SLE), we carried out a retrospective cohort study with clinical data collected from 121 consecutive patients with active SLE. Seventeen patients had infection within 6 months of beginning steroid therapy for active SLE. Independent multivariate predictors of infection were a decrease in the serum albumin value, an increase in the serum creatinine value, and prednisolone use in a dose of > or = 60 mg/day without methylprednisolone pulse therapy. The error rate of the model by 10-fold cross-validation method was 12%, sensitivity was 65%, specificity was 91%, and positive predictive value was 55%. Four nonsurvivors were correctly discriminated. Use of this model could contribute to earlier diagnosis of infection and may assist decisions regarding empiric antimicrobial administration in patients with SLE.

Adolescent↗

PubMed1996

[A dual occurrence of endometrial and gastric adenocarcinomas in systemic lupus erythematosus].

The association of systemic lupus erythematosus (SLE) and solid tumors is infrequent. Furthermore, there has been no previous description of multiple occurrence of carcinoma in a single patient with SLE. We describe clinical picture of the patient who had dual occurrence of endometrial and gastric adenocarcinomas in addition to clinically active SLE and organ system involvement.

Adenocarcinoma↗