Search PubMed⌕ Search

Biomedical subjects

A Uchida

Publications and source records attributed to A Uchida.

At least 163 records · Page 9Linked to original sources

Blood pressure at health screening as a predictor of coronary heart disease in Kyoto.

AIM: Most epidemiologic studies that have evaluated coronary risk factors have measured either mortality or morbidity of coronary artery disease (CAD) as endpoints. However, earlier detection and elimination of coronary risk factors are crucial. We therefore performed Master's double (i.e. 1.5 min x 2 = 3 min) two-step exercise electrocardiograph (ECG) test in apparently healthy asymptomatic subjects (men, n = 2274; women, n = 959) to elucidate the risk factors for early-stage CAD or silent myocardial ischemia. METHODS: We examined the possible association of blood pressure at health screening and other suspected risk factors with exercise ECG test performance. The ischemic ECG response was determined by (1) > or = 0.5 mm horizontal or sagging S-T segment depression, (2) > or = 2.0 mm J-shaped S-T segment depression, or (3) T inversion in post-exercise ECG. RESULTS: We found that 4.7% of men and 10.6% of women exhibited ischemic responses. Among males, the ischemic responders to the exercise ECG test had higher systolic and diastolic blood pressure. In addition, the male ischemic responders were older, had a higher obesity index, higher serum cholesterol, triglyceride, low-density lipoprotein (LDL)-cholesterol, protein, glucose, and uric acid levels, and a lower serum potassium level than normal responders. In contrast, the female ischemic responders to the exercise ECG test had higher systolic pressure, and higher serum cholesterol, LDL-cholesterol, and protein levels than normal responders. Mean blood pressure was correlated positively with most of the other coronary risk factors, and mild hypertensives and hypertensives had abnormal lipid, glucose, and uric acid levels in both sexes. A comparison of risk factors by age group revealed that only younger and middle-aged ischemic responders had higher blood pressure, serum cholesterol, and glucose levels than normal responders of both sexes, and that in older subjects all the differences between normal and ischemic responders became insignificant. CONCLUSIONS: Elevated blood pressure at health screening, together with abnormal lipid and glucose metabolism, might be risk factors predicting early-stage or silent CAD. The elimination of these risk factors in younger men and women seems to be important.

Adult↗

Moloney murine leukemia virus infection accelerates lymphomagenesis in E mu-bcl-2 transgenic mice.

E mu-bcl-2 transgenic mice bearing the bcl-2 proto-oncogene linked to the immunoglobulin enhancer (E mu) sporadically develop B or T cell lymphomas after a long latent period. To identify genes that play important roles in development of lymphoid malignancies, proviral insertional mutagenesis with Moloney murine leukemia virus (MMuLV) was carried out in two lines of transgenic mice expressing the bcl-2 gene primarily in B or T cells. MMuLV infection of non-transgenic mice induced primarily mature T cell lymphomas. By contrast, infection of newborn E mu-blc-2 mice with the virus accelerated lymphomagenesis, and nearly all of the mice eventually succumbed to clonal pre-B, B, or mainly immature T cell lymphoma, indicating the active contribution of the bcl-2 gene in lymphomagenesis. Southern blot analysis of tumor DNA from MMuLV-infected transgenic mice revealed a proviral insertion at the c-myc gene in 26% (9/35) of tumors, at the pim-1 gene in 6% (2/35) and at the pim-2 (recently renamed tic-1) gene in 23% (8/35). Some tumors carried two activated oncogenes. No insertion was detected at the bmi-1 gene. These data suggest the usefulness of this transgenic system for analysis of lymphomagenesis involving the activated bcl-2 gene.

Aging↗

Young borderline hypertensives are hyperreactive to mental arithmetic stress: spectral analysis of R-R intervals.

To investigate whether sympathetic tone and its reactivity to stress are increased in borderline hypertension, we compared pressor and autonomic nervous responses to mental arithmetic stress in male borderline hypertensives (BH) and normotensive volunteers (NT). Three age groups, 30, 40 and 50-year-old groups, which included 30 to 39, 40 to 49 and 50 to 59-year-old subjects, were studied. Fractional LF (%LF), fractional HF (%HF) and L/H, obtained from the power spectrum of R-R intervals, were used as indices of autonomic nervous function. Baseline autonomic nervous indices did not differ between NT and BH of any age group. Blood pressure rose higher during mental arithmetic stress in 50 than in 30-year-old NT but not in comparable age groups of BH. Pressor responses were augmented in BH compared to NT only in the 30-year-old group. However, the differences were not significant when pressor responses were expressed as percent increases in blood pressure. Both %L and L/H increased during arithmetic stress. The increase in %L did not differ between NT and BH but that in L/H (% delta L/H) was larger in 50 than in 30-year-old NT. % delta L/H was larger in BH than in NT only in the 30-year-old group. These findings suggest that both pressor and autonomic nervous responses to metal arithmetic stress were altered by aging and augmented in BH compared to NT in the 30-year-old group.

Adult↗

Suppression of pulmonary metastasis by angiogenesis inhibitor TNP-470 in murine osteosarcoma.

We treated a murine osteosarcoma cell line, LM8, which preferentially metastasizes to the lungs, with a new angiogenesis inhibitor, TNP-470, to evaluate the efficacy of this compound in the suppression of pulmonary metastasis of osteosarcoma. In an in vivo experiment, tumor cells were inoculated i.v. into C3H mice, and TNP-470 or vehicle alone (control group) was administered s.c. every day for 3 weeks. In the TNP-470-treated groups, both the number of pulmonary metastatic nodules and the lung wet weight were significantly reduced in a dose-dependent manner. Similarly, vascular density in the metastatic tumors estimated by immunohistochemical staining with anti-von-Willebrand factor antibody as an endothelial marker were significantly reduced. No severe side-effects were found. In an in vitro experiment, viable tumor cells were counted after 3 days' treatment with TNP-470. The 50% inhibitory concentration was 0.6 ng/ml for LM8, which was more sensitive than other tumor cells previously reported. Our results show that TNP-470 suppresses the pulmonary metastasis of LM8 and suggest that both its anti-angiogenic activity and cytostatic activity towards LM8 are responsible for the antitumor effect.

Animals↗

Angiosarcoma in Japan. A review of 99 cases.

BACKGROUND: Angiosarcoma is rare, and information about its clinical features are limited. Therefore, a large scale study of angiosarcoma was performed in Japan. METHODS: Through a nationwide Japanese study, 99 cases of angiosarcoma were collected and their clinicopathologic findings were summarized relative to predisposing risk factors. RESULTS: The patient age at diagnosis was 3-92 years, (mean, 62 years), with a two to one male to female ratio. The head and face were the most common primary site (29 cases); other sites were liver (17); trunk (13): pleural cavity (6), chest wall (2), abdominal wall (2), buttock (2), inguinal region (1); heart (12); and extremities (7). The proven predisposing risk factors included chronic pyothorax for angiosarcoma in the pleural cavity (six), thorotrast in the liver (five), radiotherapy to the abdominal wall and buttock (four), and chronic limb edema of the forearm (one). Irrespective of primary sites, the majority of cases had metastases to lung in 72 cases, bone in 42, liver in 36, regional lymph nodes in 30, and adrenal gland in 24. The 2-year survival rate was 17%. CONCLUSIONS: This study describes a different etiology in the development of angiosarcoma in patients from Japan compared with that of patients from Western countries, though the frequency of angiosarcoma among all soft-tissue sarcomas was similar in both areas. In Japan, chronic pyothorax, radiotherapy, and thorotrast proved to be distinctive causative factors of angiosarcoma.

Adolescent↗

Stimulation of NK-like YT cells via leukocyte function-associated antigen (LFA)-1. Possible involvement of LFA-1-associated tyrosine kinase in signal transduction after recognition of NK target cells.

The YTA-1 anti-LFA-1 alpha mAb activates protein tyrosine kinase (PTK), augments NK cytotoxicity, and induces proliferation of fresh CD3- large granular lymphocytes. We demonstrate here that LFA-1 is physically associated in the YT human NK-like cell line cells with a PTK(s) that is distinct from Src family PTKs such as Lck, Fyn, or Lyn. In vitro kinase assays revealed similar association of protein kinase activity with LFA-1 in normal CD3- large granular lymphocytes. Tyrosine phosphorylation of the proteins associated with LFA-1 drastically increased in YT cells after stimulation with NK-sensitive K562 cells but not with NK-resistant P815 cells. Furthermore, pretreatment of YT cells with TS1/22 anti-LFA-1 alpha and TS1/18 anti-LFA-1 beta mAbs abrogated not only the cytotoxicity against K562 cells but also an increase in tyrosine phosphorylation of LFA-1-associated molecules induced by K562 stimulation. These results provide biochemical evidence that the PTK(s) associated with LFA-1 is involved in the signal transduction that follows the recognition of NK target cells.

Antibodies, Monoclonal↗

Inhibition of proliferation and induction of apoptosis by abrogation of heat-shock protein (HSP) 70 expression in tumor cells.

Tumor cells often express elevated levels of heat-shock protein (HSP) 70. The present study was designed to investigate the role of HSP70 in the proliferation and survival of tumor cells in the human system. When Molt-4 and other tumor cells were treated in vitro with HSP70 antisense oligomer, they displayed propidium-iodide-stained condensed nuclei (intact or fragmented). A ladder-like pattern of DNA fragments was observed with HSP70 antisense-oligomer-treated tumor cells in agrose gel electrophoresis, which was consistent with internucleosomal DNA fragmentation. Flow cytometry analysis revealed the hypodiploid DNA peak of propidium-iodide-stained nuclei in the antisense-oligomer-treated cells. The apoptosis induced by HSP antisense oligomer was dose- and time-dependent. The antisense oligomer induced apoptosis mainly in tumor cells at G1 and S phase, resulting in an inhibition of cell proliferation. HSP70 antisense oligomer caused DNA-sequence-specific inhibition of HSP70 expression, which preceded apparent apoptosis. These results indicate that HSP70 antisense treatment inhibits the expression of HSP70, which in turn inhibits cell proliferation and induces apoptosis in tumor cells and suggest that HSP70 is required for tumor cells to proliferate and survive under normal condition.

Apoptosis↗

Monohexosylceramides of larval and adult forms of the tapeworm, Spirometra erinacei.

The occurrence of glycosphingolipids with unique carbohydrate structures in different species of cestode, Platyhelminth, which had been shown previously, prompted us to study the molecular species of the monohexosylceramides (cerebrosides) in the pseudophyllidean cestode, Spirometra erinacei. The purpose of the study was to obtain a basis for future investigations of the physiological role of glycolipids in parasitism. Cerebrosides were isolated from S. erinacei at two growth stages, i.e., from the larval form (plerocercoid) and from the adult tapeworms (intestinal form). The cerebrosides were separated into four subfractions by silica gel column chromatography, and their constituents were analyzed by gas-liquid chromatography, gas chromatography/mass spectrometry, and high-performance liquid chromatography/mass spectrometry. The hexoses of the cerebrosides consisted primarily of galactose in both growth stages, while only a small amount of glucose was detected. The ceramides were composed of sphinganine (d18:0) and phytosphingosine (t18:0) as sphingoid bases, and of nonhydroxy fatty acids ranging from C16 to C30 and hydroxy stearic acid (18h:0). The cerebrosides of adult tapeworms contained more 18h:0 than those of plerocercoids. The combination of hexoses and ceramides in the cerebroside molecules was slightly different in the two growth stages: the glucocerebrosides of plerocercoids contained only d18:0-nonhydroxy fatty acids in their ceramide moieties, whereas those of adult tapeworms contained varying ceramide moieties. Our data indicate that the molecular species of glycolipids present were essentially homeostatic throughout growth in spite of the entirely different environmental conditions, although there were slight differences in the hexose distribution in the two growth stages.

Animals↗

Keloid formation after surgery for release of polysyndactyly of the feet in a child.

Keloid formation on the hands and the feet is very rare but should always be anticipated as a possible complication after surgery. Failure to recognise the potential for keloid may result in a severe deformity that is functionally and cosmetically undesirable. We report severe keloid formation after simple release of polysyndactyly of the feet of a 2-year-old child.

Female↗

Activation of natural killer cells by the mAb YTA-1 that recognizes leukocyte function-associated antigen-1.

The mAb YTA-1, which brightly stains CD3-CD16+ large granular lymphocytes (LGL)/natural killer (NK) cells and CD8+ T cells by immunofluorescence, is specific for leukocyte function-associated antigen (LFA)-1. Some mAbs recognizing the LFA-1 alpha chain (CD11a) or LFA-1 beta chain (CD18) inhibited the binding of YTA-1 to peripheral blood mononuclear cells. YTA-1 mAb could be chemically cross-linked to 170 and 96 kDa molecules, whose molecular weights correspond to those of LFA-1 alpha and beta respectively. YTA-1 bound to COS-7 cells co-transfected with CD11a and CD18 cDNAs, but not to untransfected cells. Reactivities of YTA-1 to K562 cells transfected with LFA-1 alpha and beta (CD11a/CD18) cDNAs and to CHO cells transfected with Mac-1 (CD11b/CD18) or p150, 95 (CD11c/CD18) cDNAs strongly suggest that YTA-1 recognizes either LFA-1 alpha or an epitope formed by a combination of LFA-1 alpha and beta. Treatment of fresh CD3-CD16+ LGL with YTA-1 augmented cytolytic activity and induced proliferation. F(ab')2 fragments of YTA-1 augmented NK cytotoxicity, indicating that the NK activating signal was transmitted through LFA-1 without involvement of Fc gamma receptor III. In contrast, the other mAbs against LFA-1 could not activate NK cells. These results collectively indicate that YTA-1 recognizes a unique epitope of LFA-1, which is involved in activation of fresh NK cells.

Animals↗

Role of nitric oxide in impaired coronary circulation and improvement by angiotensin II receptor antagonist in spontaneously hypertensive rats.

1. To determine whether coronary flow regulation by nitric oxide (NO) is impaired in the hypertensive heart (HTH), coronary perfusion was measured in isolated rat hearts using NO synthesis inhibitor L-NG-monomethyl arginine (L-NMMA) in Wistar-Kyoto (WKY) rat and spontaneously hypertensive rat (SHR) with and without chronic Nomega-nitro-L-arginine-methylester (L-NAME) treatment. Moreover, the effect of angiotensin II receptor antagonist (AT1 receptor antagonist) (TCV-116) on the impaired coronary circulation in HTH was examined. 2. Coronary flow (CF) was decreased in HTH accompanied with cardiac hypertrophy. The decreased response of CF to L-NMMA infusion was diminished in HTH. It is suggested that NO production was reduced in coronary vasculature in HTH. 3. In chronic L-NAME treated SHR, blood pressure and cardiac hypertrophy were accelerated. Although coronary flow resistance (CFR) was increased, the increased response of CFR to L-NMMA infusion was not altered. 4. The AT1 antagonist improved total minimal coronary flow resistance (MCFR) restoring CFR response in SHR, although it did not recover CFR response in chronic L-NAME treated SHR. 5. Taken together the findings suggest that NO production was exhausted in the coronary artery even in the developing stage of hypertension and this exhaustion could contribute to the impairment of coronary circulation of HTH.

Angiotensin II↗

Effects of gamma-linolenic and eicosapentaenoic acids on blood pressure in SHR.

1. The present study was performed to determine whether chronic treatments with gamma linolenic acid (n-6, GLA) or eicosapentaenoic acid (n-3, EPA) would alter serum and red blood cell (RBC) unsaturated fatty acid composition, and to determine whether these treatments would affect blood pressure (BP), serum lipid metabolism and the development of atherosclerosis in spontaneously hypertensive rats (SHR). 2. To compare the effects on atherosclerosis, some SHR were denuded of aortic endothelium so that the development of atherosclerosis would be accelerated. Olive oil (control), GLA or EPA (low dose: 5 mg/day per rat, high dose: 50 mg/day per kg, respectively) was administered intraperitoneally for 6 weeks in SHR. 3. GLA treatments increased GLA and its metabolite, dihomo-GLA, levels in serum but not in RBC, while EPA treatments increased EPA level both in serum and in RBC. 4. The BP of control SHR was further elevated. EPA significantly reduced this elevation of systolic, mean and diastolic pressure within the first week and thereafter, whereas GLA did not affect BP elevation. Neither heart rate or bodyweight gain was affected by these treatments. 5. Serum total cholesterol (TC), triglyceride (TG), and glucose (G) levels and the development of atherosclerosis were unaffected by either GLA or EPA treatment. 6. In summary, chronic EPA but not GLA treatment slightly reduced BP elevation in SHR. Although chronic GLA or EPA treatment increased the respective serum level, these treatments unaltered serum TC, TG and G levels, and could not prevent the development of aortic atherosclerosis in SHR.

Animals↗

Hypothalamic and medullary GABAA and GABAB-ergic systems differently regulate sympathetic and cardiovascular systems.

1. To determine whether hypothalamic and medullary GABA (gamma-aminobutyric acid)B stimulation would affect the sympathetic and cardiovascular activities, and to determine whether these effects would be altered in hypertension, baclofen (a GABAB agonist) was injected into a hypothalamic pressor area (ventromedial hypothalamus, VMH), a depressor area (anterior hypothalamus, AH), or a nucleus tractus solitarius (NTS) in normotensive and spontaneously hypertensive rats (SHR). 2. Intracerebroventricular (ICV) injections of a GABAA agonist (muscimol, 1 mu g) decreased blood pressure (BP) and heart rate (HR). ICV injections of baclofen (2 mu g) elicited biphasic depressor and pressor effects, and these effects were abolished by a pretreatment with saclofen (GABAB antagonist, 100 mu g, icv). 3. Muscimol (400 ng) and baclofen (800 ng) injected into VMH decreased sympathetic nerve activity (SNA), BP and HR to almost similar levels, while saclofen injected into VMH increased HR without affecting BP levels. 4. The same dose of baclofen injected into AH increased BP, but muscimol (AH) did not alter BP. 5. Both muscimol and baclofen injected into NTS increased BP, but its magnitude was larger in baclofen injections. 6. Depressor and sympatho-inhibitory effects of baclofen (VMH) in SHR were larger than those in normotensive Wistar-Kyoto (WKY) rats, while pressor responses elicited by baclofen (AH) did not differ between SHR and WKY. 7. In summary, GABA reduces SNA, BP and HR through both GABAA and GABAB receptors in VMH. In addition, the GABAB system acts on AH and NTS to further regulate the cardiovascular activities. In SHR, GABAB-ergic dysfunction in VMH but not in AH might contribute to the development of hypertension.

Animals↗

Role of baroreflex and central alpha2-adrenergic receptor systems in the diurnal variation of blood pressure and heart rate in normotensive and hypertensive rats.

1. To elucidate whether baroreflex could contribute to manifest the diurnal blood pressure variations (DBPV) in normotension and hypertension, DBPV were recorded continuously via a femoral artery in awake normotensive (NT) rats and spontaneously hypertensive rats (SHR) with and without sinoaortic denervation (SAD). To determine the role of central alpha2-adrenergic receptor system in DBPV in hypertension, guanabentz (0.5-1.0 mu g/kg per min) was infused in SHR. 2. There were no differences in mean arterial pressure (MAP) variability (SD) of MAP of 24 h (MAP -- SD/MAP) and SD of 24 h heart rate (HR -- SD/HR) between SHR and NT. SAD did not elevate MAP and HR in both SHR and NT. 3. However, in SAD rats, MAP -- SD/MAP was significantly greater than those in sham-operated rats in both SHR and NT, while MAP -- SD/MAP and HR -- SD/HR did not show any difference between the two groups even after SAD. On the other hand, SAD did not augment HR -- SD/HR in either strain. 4. During guanabentz infusion, MAP was significantly lowered in sham-operated and SAD -- SHR. Moreover, MAP -- SD/MAP was significantly reduced in sham-operated, but it was not in SAD -- SHR. 5. These findings suggest that baroreflex could suppress tonically the diurnal change of blood pressure in NT and SHR. The regulation of diurnal blood pressure by baroreflex via a central alpha-adrenergic receptor system may be altered in SHR.

Adrenergic alpha-2 Receptor Antagonists↗

Transvaginal ultrasonographic morphology in polycystic ovarian syndrome.

To assess the morphological findings based on transvaginal ultrasound, the ovarian volume and the number and size of small follicles were studied in 47 patients with polycystic ovarian syndrome (PCOS) diagnosed clinically. Thirty normal volunteers served as controls. The mean ovarian volume (10.3 ml) and number of follicles (10.6) in patients with PCOS were significantly higher than those of controls. An ovarian volume > 6.2 ml and follicles > 10 with a diameter of 2-8 mm were the most prominent features in the ovaries of patients with PCOS and 94% of 47 patients with PCOS had at least one of these ultrasonic findings. However, marked asymmetry of the two ovaries was seen in about 50% of patients with PCOS and a considerable overlap existed between controls and patients with PCOS in the ovarian volume and in the number of follicles. Three (6%) patients with normal ovarian volume and normal number of follicles were observed. Therefore, it is difficult to clearly distinguish a patient with PCOS from a normal woman only by transvaginal ultrasonic criteria using the ovarian volume and/or the number of follicles, although these criteria could be clinically useful for the screening of PCOS.

Adult↗

Accumulation of gamma/delta T cells in human dysgerminoma and seminoma: roles in autologous tumor killing and granuloma formation.

The precise biological function of a subset of T cells bearing gamma/delta T cell receptor (TCR) remains poorly understood. The present study demonstrated the presence of gamma/delta T cells in tumor-infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) of human patients with dysgerminoma and seminoma when determined by flow cytometry and in situ immunohistochemical staining. TIL contained a high percentage of gamma/delta T cells, ranging from 17.3 to 35.1%. gamma/delta T cells often accumulated within the granulomatous inflammation of tumor tissues. The majority of gamma/delta T cells were V gamma 9/V delta 2+ cells. Freshly isolated PBL, TIL and purified gamma/delta T cells showed autologous tumor killing (ATK) activity, which could be inhibited by monoclonal antibodies (mAb) against V delta 2. Furthermore, two gamma/delta T cell clones established from TIL showed cytotoxicity against autologous and allogeneic dysgerminoma, while they had low or no lytic effects on other cell types including carcinomas of ovary and tumor cell lines such as K562, Daudi and Molt-4. Lysis of autologous tumor cells by the clone was inhibited completely by anti-V delta 2 mAb and partially by mAb against CD3, LFA-1 alpha and ICAM-1 molecules, while it was resistant to anti-CD8, anti-HLA-ABC and anti-HLA-DR mAb. Supernatants produced by gamma/delta T cell clones induced adhesion, aggregation and increased DNA synthesis of monocytes and some characteristics of activated macrophages or epithelioid cells. Tumor necrosis factor (TNF)-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon (IFN)-gamma were detected in the supernatants of gamma/delta T cell clone. These results suggest that gamma/delta T cells accumulating in dysgerminoma and seminoma exhibit ATK activity through V gamma 9/delta 2 TCR and these gamma/delta T cells also play a role in the formation of granulomatous inflammation, which is associated with human dysgerminoma and seminoma.

Adult↗

[Use of semirigid ureteroscopes for treatment of ureteral calculi].

BACKGROUND: The objective of this study is to evaluate the efficacy of ureteroscopic lithotripsy as the treatment of ureteral stones in the recent era by comparing the result using a semirigid ureteroscope with the result using a conventional ureteroscope. METHODS: Between 1991 and 1994, 136 patients with ureteral calculi underwent transurethral ureteroscopic lithotripsy in our hospital. From July 1991 to March 1993, 14F rigid ureteroscope with the rod lens system was used for 82 patients (group 1), whereas from April 1993 to July 1994 either a 9.5F or 7F semirigid fiberoptic ureteroscope was used for 54 patients (group 2). Insertion of ureteroscopes was performed under continuous irrigation of saline without mechanical dilation of the ureteral orifice in both groups. RESULTS: The rates of complete removal of stone at the first trial were 56.1% in group 1 and 72.2% in group 2 with the overall complete removal rate of 62.5%. The complete removal rates of stones in the upper, middle and lower ureters were 18.2%, 54.8% and 72.4% in group 1 and 14.3%, 72.7% and 88.0% in group 2, respectively. The major reasons for unsuccessful treatments was upward migration of stones during the procedure. As intraoperative complications, ureteral disruption occurred in 1 case in group 1, and ureteral perforation in 5 patients in group 1 (6.1%) and 2 in group 2 (3.8%). Acute bacterial infection with prolonged fever was observed in 3 patients in group 1 and in none in group 2. CONCLUSION: From these results, the new semirigid ureteroscope with fiberoptic imaging bundles made the transurethral lithotripsy a safer and more efficient procedure for the treatment of ureteral calculi especially those in the lower ureters.

Adolescent↗