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Biomedical subjects

Y Yamamura

Publications and source records attributed to Y Yamamura.

At least 145 records · Page 8Linked to original sources

Epidemiology of nonmelanoma skin cancer.

In summary, the cause of NMSC is multifactorial and complex. The interaction among environmental and lifestyle factors along with host factors determines the development and progression of NMSC. Despite the relatively benign nature of NMSC, rising incidence rates in an aging population will result in increased medical costs, morbidity, and mortality. Frequent exposure to UVR, fair skin, and reduced immunity, possibly related to aging, are the major risk factors. Because UVR exposure is responsible for most of the NMSC cases, the key to reducing the number of skin cancers is through prevention, mainly by reducing exposure to sunlight, and further exploration of possible chemopreventive agents. To understand better the complex causes of NMSC and to evaluate prevention strategies, further population-based research is necessary.

Basal Cell Carcinoma↗

Finding association rules on heterogeneous genome data.

A novel approach for discovery of knowledge from genome data, which has been recently watched with interest in the research area of database, is applied to finding unified rules spreading over sequence, structure, and function of protein. As the result of experiments using data extracted from PDB, SWISS-PROT, and PROSITE, some association rules stating sequential/structural/functional aspects of two kinds of endopeptidases were found.

Computer Simulation↗

Mechanisms associated with defective TH1 cytokine production in HIV infection.

Qualitative and quantitative changes in immune functions of different T-cell subsets associated with infection by human immunodeficiency virus type 1 (HIV-1) were analyzed by flow cytometric assessment of intracytoplasmic cytokines. The T(H)1 cytokines, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), were produced by both CD4 and CD8 T-cell subsets. When normal peripheral blood mononuclear cells (PBMC) were activated in culture, both cytokines were produced predominantly by CD4 (CD4) cell and only a minor fraction of normal CD8 cells produced these cytokines. In the cultures of PBMC from HIV-1-infected individuals (HIV+PBMC), more HIV+CD8 cells produced IL-2 and IFN-gamma. Production of IFN-gamma by HIV+CD4 cells was markedly reduced, while IL-2nd tumor necrosis factor-alpha (TNF-alpha) production by HIV+CD4 remained relatively intact until the disease progressed further. Normal CD4 cells which were isolated by using a cell sorter, FACSCalibur was still able to produce IL-2 and TNF-alpha. But for full production of IFN-gamma, normal CD4 required some accessory cells, the identity of which could not yet be established.

CD4-Positive T-Lymphocytes↗

The proliferative response of HIV+ T-cells (CD4+ and CD8+) are severely suppressed via CD28 coactivation.

Several studies have suggested that regulation of expression of the costimulatory molecule CD28 on the T-cell surface may play an important role in AIDS pathogenesis. In a study of T-cells from HIV+ donors, we find that activation with anti-CD3 plus anti-CD28 results in a mitogenic response which was approximately 86% suppressed for both CD4+ and CD8+ T-cells when compared to normal control cells. With PMA costimulation (instead of anti-CD28), the anti-CD3 response was suppressed much less, by 64 and 61%, respectively. With Con A as opposed to CD3 stimulation, the degree of suppression was less with either coactivator but still more severe with CD28 than with PMA coactivation. It has been reported that the CD28 subset of CD8+ T-cells is diminished in HIV+ individuals and could account for these results. It is possible as well that the CD28 costimulatory pathway in the CD4+ T-cells particularly is altered due to intervention by the HIV. While our data do not differentiate between these two possibilities, it show that the immune status is compromised in the HIV+ individual not only in terms of number of CD4+ T-cells, but in their activation response as well.

Adult↗

Pattern of injecting drug uses and HIV-1 infection: analysis from needle exchange program.

Contents of exchanged needles/syringes were analyzed to examine: i) the prevalence of HIV-1 infection among injecting drug users (IDU's), and ii) the classes of drugs injected by the population. A needle exchange program in Puerto Rico (PR) was initiated under the auspices of the PR Department of Health and is currently being administered by the Community Research Initiative of Puerto Rico, Inc. Serological tests for human immunodeficiency virus type 1 (HIV-1) were performed with 387 samples with clearly visible amounts of blood, which were chosen randomly from the needle exchange program of the San Juan Metropolitan area on the north coast, and also of the Mayaguez area on the west coast of the island. In addition, 200 syringes without visible amount of blood were also randomly chosen, their contents were extracted with acidified methanol and analyzed by gas chromatography-mass spectrometry (GC/MS) for drug content. One hundred and ninety four of the samples (58%) were confirmed to be positive for HIV-1. Four samples contained heroin alone, 190 were positive for cocaine and 2 indicated simultaneous use of both heroin and cocaine. In contrast to existing literature, based mostly on self-description, which indicates widespread use of heroin and cocaine mixture ("speedball") among IDU's, our physical evidence suggests that a large majority of IDU's in PR currently inject cocaine but not heroin; and also that mixed drug use is rather rare. Reliability of self-described information may need to be re-evaluated.

Gas Chromatography-Mass Spectrometry↗

Effects of acupuncture on behavioral, cardiovascular and hormonal responses in restraint-stressed Wistar rats.

Stress is a well-known entity and may be defined as a threat to the homeostasis of a being. In the present study, we evaluated the effects of acupuncture on the physiological responses induced by restraint stress. Acupuncture is an ancient therapeutic technique which is used in the treatment and prevention of diseases. Its proposed mechanisms of action are based on the principle of homeostasis. Adult male Wistar EPM-1 rats were divided into four groups: group I (N = 12), unrestrained rats with cannulas previously implanted into their femoral arteries for blood pressure and heart rate measurements; group II (N = 12), rats that were also cannulated and were submitted to 60-min immobilization; group III (N = 12), same as group II but with acupuncture needles implanted at points SP6, S36, REN17, P6 and DU20 during the immobilization period; group IV (N = 14), same as group III but with needles implanted at points not related to acupuncture (non-acupoints). During the 60-min immobilization period animals were assessed for stress-related behaviors, heart rate, blood pressure and plasma corticosterone, noradrenaline and adrenaline levels. Group III animals showed a significant reduction (60% on average, P < 0.02) in restraint-induced behaviors when compared to groups II and IV. Data from cardiovascular and hormonal assessments indicated no differences between group III and group II and IV animals, but tended to be lower (50% reduction on average) in group I animals. We hypothesize that acupuncture at points SP6, S36, REN17, P6 and DU20 has an anxiolytic effect on restraint-induced stress that is not due to a sedative action.

Acupuncture Therapy↗

Orally active, nonpeptide vasopressin V2 receptor antagonists: a novel series of 1-[4-(benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepines and related compounds.

This paper describes a novel series of nonpeptide vasopressin V2 receptor antagonists. It has been demonstrated that the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepines and 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-1,5-benzodiazepines show a high affinity for V2 (and V1a) receptors. Among the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepine series, compounds with an alkylamino group on the benzazepine ring have been shown to have oral activity. A lipophilic group at the ortho position on the terminal benzoyl ring is important for both high V2 receptor affinity and oral activity. On the basis of these favorable properties, clinical testing of 31b has begun for use as an oral and iv aquaretic agent.

Administration, Oral↗

Gastric stump carcinoma after partial gastrectomy for benign gastric lesion: what is feasible as standard surgical treatment?

METHOD: Clinicopathological features and prognostic factors were evaluated in 26 cases of stump carcinoma, operated on in the recent 20 years, in search of the standard surgical treatment. BACKGROUND: Stump carcinoma usually emerges more than 20 years after the initial gastrectomy and is often not diagnosed in the early clinical stage, resulting in a significantly low incidence of curative resection compared with primary gastric carcinoma. RESULTS: No improvement in the survival curves for stump carcinoma was observed between the past two decades. Nodal metastases were frequently found within the first tier nodes, and no 5-year survivor was found among the patients with nodal metastasis beyond pN1. CONCLUSIONS: Subtotal gastrectomy might suffice for the treatment of stomal cancer, and most patients might not benefit from extensive lymphadenectomy.

Carcinoma↗

Characterization, molecular cloning and expression of megakaryocyte potentiating factor.

We examined whether the conditioned media of 64 kinds of cell lines, which have been maintained by a protein-free culture system, could produce megakaryocyte potentiating (Meg-POT) activity. In these cell lines, HPC-Y5, established from human pancreatic cancer, was shown to have the highest level of activity. The megakaryocyte potentiating factor (MPF) was purified from its conditioned medium by a combination of ion-exchange chromatography, gel filtration and reversed-phase HPLC. The purified MPF showed Meg-POT activity almost equal to human (Hu) interleukin 6 (IL-6) in the presence of murine IL-3 in a colony-forming assay with mouse bone marrow cells. The molecular weight of MPF was estimated to be 33 kDa by SDS-PAGE. Glycopeptidase F digestion and amino sugar analysis of the factor demonstrated that MPF is a glycoprotein carrying at least one N-linked sugar chain. The N-terminal amino acid sequence of MPF was determined to be Leu-Ala-Gly-Glu-Thr-Gly-Gln-Glu-Ala-Ala-Pro-Leu-Asp-Gly-Val-Leu-Ala-Asn. The same or homologous amino acid sequence has not been found in known proteins, demonstrating that MPF may be a novel cytokine which has Meg-POT activity. Then, we isolated HuMPF cDNA from an HPC-Y5 cDNA library using polymerase chain reaction and plaque hybridization methods. The HuMPF cDNA encodes a polypeptide consisting of 622 amino acids, including a signal peptide of 33 amino acids, and with a deduced molecular weight of 68 kDa, although HPC-Y5 cells secrete a 33 kDa form of HuMPF. HuMPF cDNA does not show any significant homology with other known sequences. The cDNA was expressed in COS-7 and Chinese hamster ovary (CHO) cells, and Meg-POT activity was detected in their culture supernatant. The COS-7 cells secreted only a 33 kDa recombinant (r)HuMPF, however, an additional 30 kDa form was detected in the culture medium of CHO cells. The 33 kDa rHuMPF from CHO cells showed Meg-POT activity, but not the purified 30 kDa rHuMPF. The difference in structure and activity between the 33 and 30 kDa forms of HuMPF was ascribed to the existence in the 33 kDa form of the C-terminal 25 amino acid residues. The expression of MPF mRNA was examined by Northern blot analysis using labeled MPF cDNA as a probe. MPF mRNA was detected in HPC-Y5 cells, with an approximate molecular size of 2.4 kb. We also examined the expression of the MPF gene in various human tissues, and the 2.4 kb band was detected only in lung. Then, the immunohistocytochemical analysis and in situ hybridization revealed that MPF-producing cells were identified as lung macrophages. MPF may exhibit other biological activities such as regeneration of the lung tissues.

Amidohydrolases↗

Morphological study of cytotoxicity produced by PSK-induced polymorphonuclear leukocytes (PMNs) and Nocardia rubra cell wall skeleton.

The morphologic changes in PMNs induced by an i.p. injection of PSK, a polysaccharide from the mycelia of Coriolus versicolor, and tumor cells undergoing cell death, were evaluated by immunohistochemical staining and electron microscopy. Male C3H/He mice, 8-10 -weeks old, received an i.p. injection of 125 mg/kg of PSK. Their PMNs were obtained 6 h after the PSK injection by peritoneal lavage. N-CWS (Nocardia rubra cell wall skeleton) was added at the start of the chromium release assay using the MM46 mammary carcinoma cell line, which is syngeneic to C3H/He mice, as target cells. During the cytotoxic assay, the cells were fixed at various time points. The MM46 cells expressed ICAM-1 while the PMNs expressed both ICAM-1 and LFA-1 as determined by immunohistochemical staining and immunoelectron microscopy using anti-ICAM-1 and anti-LFA-1 antibodies. PMNs with ruffle-like microvilli adhered to the MM46 tumor cells 30 min after the addition of N-CWS. Immunoelectron microscopic findings suggested that the adhesion molecules were LFA-1 on the PMNs and ICAM-1 on the MM46 tumor cells, but cell fusion between the PMNs and tumor cells was not observed. The MM46 tumor cells gradually lost their microvilli, which showed cell damage, and died 6-7 h after the addition of the N-CWS. This time course of tumor cell death is compatible with the results of the cytotoxic assay. Pretreatment of PMNs by anti-LFA-1 antibody suppressed 1% lysis of MM46 tumor cells from 90% to 10% (p < 0.01). These data suggest that adhesion molecule on the surface of PMNs such as LFA-1 might play an important role on signal transduction of these PMNs cytotoxic function in this experimental system.

Adjuvants, Immunologic↗

In vitro chemosensitivity of human pancreatic cancer cell lines.

CONCLUSION: These results show that eight pancreatic cancer cell lines are broadly sensitive to CDDP, and that chemotherapy for pancreatic cancer may improve the prognosis by more effective drug delivery to cancer cells. BACKGROUND: Chemotherapy for pancreatic cancer does not satisfactorily improve prognosis. The efficacy of chemotherapy depends on choosing sensitive anticancer drugs. METHODS: The in vitro chemosensitivity of eight human pancreatic cancer cell lines was investigated. Growth inhibition was measured by 3H-thymidine incorporation assays for doxorubicin hydrochloride (ADM), mitomycin C (MMC), cisplatin (CDDP), and etoposide (VP-16), and by Alamar Blue assay for (AB assay) 5-fluorouracil (5-FU). The cells were exposed to ADM, MMC, CDDP, and VP-16 for 2 h, and 5-FU for 72 h. From the dose-response curves, the 50% growth inhibition (IC50) level for each drug was estimated. RESULTS: The IC50 after 2 h of exposure of each of the eight kinds of cell lines to each anticancer drug ranged from 0.12-8.2 micrograms/mL for ADM, 0.066-25 micrograms/mL for MMC, 0.57-7 micrograms/mL for CDDP, 0.68-300 micrograms/mL for VP-16. IC50 after 72 h of exposure to 5-FU ranged from 1.8-23 micrograms/mL.

Aged↗

Efficacy of in vitro sensitized cells generated by in vivo priming with OK-432 for adoptive immunotherapy of the poorly immunogenic B16-Bl6 melanoma.

We investigated the efficacy of the streptococcal preparation OK-432 as an adjuvant for in vivo priming in induction of sensitized cells for adoptive immunotherapy of the poorly immunogenic B16-BL6 (BL6) melanoma. C57BL/6 (B6) mice were immunized subcutaneously (s.c.) with 3 x 10(6) viable BL6 tumor cells admixed with various doses of OK-432 ranging from 1 to 100 micrograms in the foot-pad. Draining popliteal lymph nodes (LNs) were harvested 7 days after immunization and LN cells were further sensitized with irradiated tumor cells in the presence of 60-300 IU/ml of IL-2 for 11 days. These in vitro sensitized (IVS) cells (2 x 10(6)) were transferred intravenously (i.v.) to B6 mice bearing 4-day pulmonary metastases established by i.v. injection of 2-4 x 10(5) viable BL6 cells. The mice were also received intraperitoneally (i.p.) 4 x 10(4) IU/day of IL-2 for 4 days after adoptive transfer. Transfer of IVS cells from mice immunized by s.c. injection of tumor cells admixed with 10 micrograms of OK-432 significantly reduced the numbers of BL6 pulmonary metastases compared with that of control IVS' cells without the administration of OK-432 (P = 0.003). These effective IVS cells also significantly prolonged the survival of treated animals (P = 0.003). Functional IVS cells required in vitro stimulation with tumor cells. However, addition of OK-432 in the vaccine resulted in no enhancement of in vitro cytotoxicity and no characteristic change of phenotype of IVS cells. These results suggest that in vivo priming of OK-432 facilitates the sensitization of tumor-reactive T-cells. The procedure of in vivo priming with OK-432 may be beneficial in the adoptive immunotherapy of melanoma.

Animals↗

Concentrations of trichloroethylene and its metabolites in blood and urine after acute poisoning by ingestion.

A 58-year-old man fell into a trichloroethylene reservoir bath head first, during a maintenance degreasing bath and accidentally ingested the solvent. Although he showed deep coma, chemical burns and pneumonia on admission, these symptoms gradually subsided. The concentrations of trichloroethylene (TRI) and its metabolites, trichloroethanol (TCE) and trichloroacetic acid (TCA) in blood and urine were measured during hospitalization. Eight hours after the accident, the concentrations of TRI and its metabolites in serum were 31.4 micrograms/ml TRI, 16.5 micrograms/ml TCE and 79.5 micrograms/ml TCA. The serum TRI concentration decreased to 4.3 micrograms/ml on the following day. Elimination of TCE and TCA from serum occurred biphasically, the estimated half-lives of each metabolites being about 52.6 and 50.4 h in an initial fast phase and 268.3 and 277.2 h in a subsequent slow phase, respectively. Urinary TRI excretion persisted for the first 2 days. The urinary TCE and TCA excretions were longer than that of TRI with a biphasic decrease and the total amount of TCE excreted during the first 2 days was about two times that of TCA. The half-life of urinary TCE excretion (t1/2 25.7 h) was shorter than that of TCA (t1/2 52.1 h) in the fast phase but did no difference during the slow phase, with each half-time being about 166.3 h. The kinetics of TRI metabolites in blood and urine in this case were in slight agreement with the results following inhalation exposure previously reported in the literature.

Accidents, Home↗

Postoperative staging of gastric carcinoma. A comparison between the UICC stage classification and the 12th edition of the Japanese General Rules for Gastric Cancer Study.

BACKGROUND: The feasibility of the latest edition of the Japanese General Rules for Gastric Cancer Study (GRGCS) is evaluated by comparison with the TNM system. METHODS: In a 5-year period from 1985 to 1989, 978 patients with gastric cancer underwent laparotomies at the Dept. of Gastroenterological Surgery, Aichi Centre Centre, Japan. All the patients have now been followed up for 5 years or until death. These patients were retrospectively classified into appropriate clinical stages and residual tumour status on the basis of the GRGCS and the 4th edition of the TNM classification by the UICC, and survival curves for various stages and subgroups were evaluated. RESULTS: The GRGCS classification provided useful information by splitting UICC stage IV into stages IVa and IVb, and R0 into curabilities A and B, both subgroups showing significant differences in the survival curves. CONCLUSIONS: The new edition of the GRGCS can be recommended as a useful staging manual for gastric cancer.

Follow-Up Studies↗

[Bone mineral density of the calcanei dissected from 30 cadavers--correlation of the values measured by the DXA, QCT and USD methods].

The bone mineral density (BMD) of calcanei dissected from 30 cadavers (14 males and 16 females; ages 61 to 100) was measured by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), while the stiffness was measured by ultrasound bone densitometry (USD). There was high correlation between BMD by DXA and average bone density by QCT (R = 0.94), but poor correlation between BMD by DXA and stiffness by USD (R = 0.55). However, the correlation coefficient of stiffness to BMD was much higher in the female calcanei (R = 0.74) than in the male calcanei (R = 0.32). Analyzing the three elements, stiffness, speed of sound (SOS) and broad-band ultrasound attenuation (BUA), it was clear that SOS rather than stiffness correlated strongly to BMD by DXA and to bone density of trabeculated bones by QCT (R = 0.618; 0.699 respectively). The value of BUA shows more relationship to the width of the calcanei than the area of X-ray projection from the side (R = 0.561).

Absorptiometry, Photon↗

Gastric remnant carcinoma after partial gastrectomy for benign and malignant gastric lesions.

BACKGROUND: A retrospective study was designed to evaluate the clinicopathologic characteristics and prognosis of gastric stump carcinoma (GSC) after gastrectomy for gastric adenocarcinoma. STUDY DESIGN: A comparison of the clinicopathologic features was made between 12 cases of GSC and 27 cases of remnant carcinoma (RC) following gastrectomy for adenocarcinoma. The various factors influencing survival of both groups of patients were evaluated separately and by multivariate analysis. RESULTS: Gastric stump carcinoma emerges late after initial gastrectomy and has a significant tendency toward lymph node metastasis. No difference was observed between the survival curves for patients with GSC or RC after gastrectomy for malignancy. Serosal invasion was the factor most affecting survival. CONCLUSIONS: Early diagnosis is most important for management of the disease, and only patients with T2 staged GSC according to the Union Internationale Contre le Cancer classification system might benefit from extensive lymphadenectomies.

Adenocarcinoma↗