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Biomedical subjects

Y Yamazaki

Publications and source records attributed to Y Yamazaki.

At least 55 records · Page 3Linked to original sources

A study on angiogenesis-related matrix metalloproteinase networks in primary hepatocellular carcinoma.

Matrix metalloproteinases (MMPs) specially degrade extracellular matrix (ECM) proteins and are involved in tissue remodeling and angiogenesis. Therefore, studies on the role of MMPs in the carcinogenesis, proliferation and infiltration of hepatocellular carcinoma (HCC) may greatly contribute to the development of a new clinically applicable therapeutic approach. In the present study, we immunologically examined the expression rates of various MMPs including MMP-2, 3, 7, 9, membrane type 1-MMP (MT1-MMP), and MT2-MMP in the cancerous and noncancerous areas of resected tumor specimens from 30 patients with primary HCC. The rate of MMP-2 expression was high for both cancerous and noncancerous areas. However, the expression rates of MMP-3, MT1-MMP, and MT2-MMP were significantly higher in cancerous areas than in noncancerous areas. Next, we examined the clinicopathologic features such as the number of tumor nodules, maximal tumor size, presence or absence of capsular infiltration and portal vein invasion, histological grades of HCCs, state of noncancerous areas (chronic hepatitis: CH or liver cirrhosis: LC), and short-term recurrence after resection (within six months). In conclusion, it was found that three main networks of MMPs are predominantly involved in the case of HCC, that is, MMP-2 and MT1-MMP in the carcinogenesis and progression, MMP-7 and MMP-9 in the capsular infiltration and portal vein invasion, as well as MMP-3 and MMP-7 in the progression of HCC. Furthermore, MT1-MMP appeared to be the most important factor in HCC because of its widespread pattern of expression.

Carcinoma, Hepatocellular↗

Impaired interleukin-1beta converting enzyme (ICE) activity in patients with pulmonary tuberculosis.

We measured the activity of IL-1beta converting enzyme (ICE) of monocytes from pulmonary tuberculosis (PTB) patients. Peripheral blood mononuclear cells (PBMCs) and serum were collected from PTB patients (n = 16) and healthy subjects (n = 6). Serum IL-18 levels were significantly higher in PTB patients (515.9 +/- 326.5 pg/ml) than in controls (108.7 +/- 65.2 pg/ml) (P < 0.01), but gradually decreased with tuberculosis therapy. ICE activity was significantly lower in TB patients (65.3 +/- 34.4 vs. 142.2 +/- 75.6 U/mg) (P < 0.05). Serum IL-18 levels inversely correlated with ICE activity (P < 0.05). Altered ICE activity may explain why there is reduced IFN-gamma production from PBMCs; however, serum IL-18 is probably not regulated by ICE in monocytes in TB patients.

Caspase 1↗

Long-term outcome after allogeneic bone marrow transplantation for hematological malignancies with non-remission status. Results of a single-center study of 24 patients.

To investigate the problem of allogeneic bone marrow transplantation (allo-BMT) for advanced stage patients, we retrospectively analyzed 24 consecutive patients who underwent allo-BMT in the non-remission stage. Twenty-four patients (19 males and 5 females) with acute leukemia, chronic myelogenous leukemia, and malignant lymphoma underwent allo-BMT. The patients had a median age of 30 years. There were eight cases of acute myelogenous leukemia (AML), six cases acute lymphocytic leukemia (ALL), nine cases of chronic myelogenous leukemia (CML), and one case of Burkitt's lymphoma. The 3-year overall survival rate was 22.5%, with a median survival time of 206 days in AML, 345 days in ALL, and 363 days in CML. Overall survival was associated with a recovery of platelets of less than 30 days and an acute graft-versus-host disease (acute GVHD) presence of less than grade II ( p=0.042). Fourteen patients died of transplantation-related diseases. Our important problem is to decrease transplantation-related deaths in allo-BMT during the non-remission stage, and longer survival can be expected with better pretreatment and prophylaxis for GVHD. In addition, the selection of the source of hematopoietic stem cell transplantation at an optimal time is considered to be another problem to be approached.

Adolescent↗

Electron cooling of high-energy protons in a multiring trap with a tank circuit monitoring the electron-plasma oscillations.

Electron cooling of energetic protons in a multiring trap was investigated experimentally with a tank circuit monitoring electron-plasma oscillations in the trap. The energy of protons was determined by time-of-flight measurements. It is found that a simple model can explain the qualitative behavior of both electron and proton energy when the initial energy of protons is less than 2 keV. Monitoring the electron-plasma temperature with a tank circuit can be an effective tool when energetic particles are electron cooled in a multiring trap.

Journal Article↗

Sex-role orientation, marital status and mental health in working women.

The objectives of this study were to make a men-women comparison as to the effects of job stress and sex-role orientation on mental health and to determine if marital status modifies effects of job stress and sex-role orientation on mental health in women. Subjects were 644 men and 301 women who were working at two private companies and one national agency. Job contents, sex-role orientation and mental health were measured by the Job Content Questionnaire, the Bem Sex-Role Inventory and the 30-item General Health Questionnaire, respectively. High job demands and femininity in men, masculinity in women predicted poor mental health. The best predictor of poor mental health was consciousness of being a woman in unmarried women, and stress outside the job in married women.

Adolescent↗

Three-dimensional distribution of the clear zone of migrating osteoclasts on dentin slices in vitro.

Osteoclasts are cells that dynamically alternate resorption and migration on bone surfaces, and have the special structure called ruffled borders and clear zones by transmission electron microscopy (TEM). However, TEM features, especially the distribution of the clear zone of osteoclasts during migration, remains unclear. This study aimed to examine osteoclasts cultured on dentin slices by TEM and clarify the features of migrating osteoclasts, especially the three-dimensional distribution of clear zones. Osteoclasts obtained from mice were cultured with dentin slices for 72 h, and then cells were fixed and the tartrate-resistant acid phosphatase (TRAP) activity was detected. Specimens were embedded in Epon, then TRAP-positive cells were serially sectioned by alternating semithin and ultrathin sections. The cells were examined by TEM and the three-dimensional structures were reconstructed by computer. By TEM, most TRAP-positive cells were resorbing osteoclasts with ruffled borders and a clear zone. There were osteoclasts without ruffled borders, and these cells had clear zone-like structures and lamellipodia. The three-dimensional reconstruction showed that resorbing osteoclasts had rounded contours and ring-shaped clear zones encircling ruffled borders, and that osteoclasts without ruffled borders had irregular and flat shapes; the clear zone-like structures showed a dot or patch-like distribution. The presence of lamellipodia of the osteoclasts without ruffled borders shows that the cells are migrating osteoclasts. These results suggest that dot or patch-like distribution is the feature of the clear zone of osteoclasts during migration, and that these structures play the role of focal contacts and adhesion to the dentin surfaces during cell migration.

Acid Phosphatase↗

Eradication of Helicobacter pylori infection induces an increase in body mass index.

BACKGROUND: The relationship between H. pylori infection and body mass indices is controversial. AIM: To investigate the relationship between H. pylori infection and body indices, and to examine the effect of H. pylori eradication therapy on body indices. METHODS: Nine-hundred and thirty-two employees of an industrial corporation were examined for H. pylori infection and body mass indices. Three hundred and two H. pylori-positive cases diagnosed with chronic gastritis by upper gastrointestinal endoscopy or radiography underwent eradication therapy. Body mass indices, serum total cholesterol levels and symptom scores were obtained before and at 12 months after eradication therapy. RESULTS: There was no significant difference in body weight, body mass index (BMI) or serum total cholesterol level between the H. pylori-positive and H. pylori-negative groups. However, body weight and BMI increased significantly 12 months after eradication of H. pylori infection. In contrast, there was no significant difference in body weight and BMI 12 months after eradication therapy in the non-eradication group. Serum total cholesterol levels did not change after eradication therapy in either the eradication or non-eradication groups. CONCLUSION: Eradication of H. pylori infection induced an increase in BMI in industrial workers with chronic gastritis in Japan.

Adult↗

Amelanotic malignant melanomas of the oral mucosa.

Oral amelanotic melanomas are rare and the prognosis is poorer than that of pigmented melanomas because of delays in establishing the correct diagnosis and in the initiation of treatment. Amelanotic forms are also thought to be biologically more aggressive than pigmented melanomas. We have seen three cases of oral amelanotic melanomas since 1970, in two of whom the diagnosis was long delayed. Two lesions were not pigmented but one had slight pigmentation. One patient simultaneously had both an amelanotic and a pigmented melanoma in the oral cavity. Lymph node metastases and distant metastases developed in all patients, two of whom eventually died of the disease. Early diagnosis by histological examination together with immunostaining with S100 and HMB-45 are the keys to improve survival for patients with amelanotic melanoma.

Aged↗

How HIV infected haemophiliacs in Japan were informed of their HIV-positive status.

The purpose of this study is to find out how HIV-infected haemophiliacs were informed and notified of their HIV infection. Self-reporting questionnaires were mailed to approximately 500 patients, about one half of the haemophiliac patients with HIV in Japan. The response rate was about 57% (n=283); and 270 (male=269) patients, apart from secondary and tertiary infected patients, were eligible as subjects for the study. The mean age was 31.2 +/- 9.9 years. Of these subjects, approximately 60% did not receive explanation regarding the risk of HIV infection via unheated blood products. More than 60% did not receive notification until 1990, or five years after the test became available in Japan. Contents of the explanations being given at the time of notifications were poor. In this paper, some problems of notifications of medically induced HIV are discussed, and the lack or delay of explanation/notification is concluded to be a consequence of the paternalistic attitudes of Japanese physicians and the iatrogenic nature of HIV infection.

Adolescent↗

A novel non-viral gene transfer system, polycation liposomes.

To develop a novel non-viral gene transfer system, liposome was modified with cetylated polyethylenimine (PEI). This polycation liposome (PCL) showed remarkable transfection efficiency to COS-1 cells in vitro, in comparison with conventional cationic liposome preparations. Cytotoxicity against COS-1 cells and hemolytic activity of PCL or PCL-DNA complex were quite low in comparison with conventional cationic liposomes. Most conventional cationic liposomes require phosphatidylethanolamine or cholesterol as a component, though PCL did not. Egg yolk phosphatidylcholine- and dipalmitoylphosphatidylcholine-based PCL were as effective as dioleoylphosphatidylethanolamine-based PCL for gene transfer. Furthermore, the transfection efficacy of PCL was enhanced, instead of being diminished, in the presence of serum. Effective gene transfer was observed in all eight malignant and two normal line cells tested as well as in COS-1 cells. The effect of the molecular weight of PEI on PCL-mediated gene transfer was examined, and observed that PEIs with a molecular weight (Mr. Wt.) of 600 and 1800 Da were quite effective but PEI of 25,000 was far less effective. Effectiveness of gene transfer by using PCL was also observed in vivo: GFP and Luciferase genes were effectively expressed in mouse. We also discussed the mechanism of gene transfer by PCL. Taken together, PCL represents a new system useful for transfection and gene therapy.

Animals↗

Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer.

When neural cells were collected from the entire cerebral cortex of developing mouse fetuses (15.5-17.5 days postcoitum) and their nuclei were transferred into enucleated oocytes, 5.5% of the reconstructed oocytes developed into normal offspring. This success rate was the highest among all previous mouse cloning experiments that used somatic cells. Forty-four percent of live embryos at 10.5 days postcoitum were morphologically normal when premature and early-postmitotic neural cells from the ventricular side of the cortex were used. In contrast, the majority (95%) of embryos were morphologically abnormal (including structural abnormalities in the neural tube) when postmitotic-differentiated neurons from the pial side of the cortex were used for cloning. Whereas 4.3% of embryos cloned with ventricular-side cells developed into healthy offspring, only 0.5% of those cloned with differentiated neurons in the pial side did so. These facts seem to suggest that the nuclei of neural cells in advanced stages of differentiation had lost their developmental totipotency. The underlying mechanism for this developmental limitation could be somatic DNA rearrangements in differentiating neural cells.

Animals↗

Use of real-time PCR on blood samples for diagnosis of invasive aspergillosis.

We developed a new quantitative system for diagnosis of invasive pulmonary aspergillosis (IPA) using real-time automated polymerase chain reaction (PCR). Intra-assay and interassay precision rates for in vitro examination were 2.53% and 2.20%, respectively, and the linearity of this assay was obtained when there were >20 copies/well. We examined 323 samples taken from 122 patients with hematological malignancies, including 33 patients with IPA and 89 control patients. Blood samples were subjected to PCR antigen detection methods, using enzyme-linked immunosorbent assay (ELISA) and determination of plasma (1-->3)-beta-D-glucan (BDG) concentration. The sensitivities of PCR, ELISA, and BDG measurement for diagnosis of IPA were 79%, 58%, and 67%, respectively; the specificities were 92%, 97%, and 84%. Positive findings on PCR preceded those of computed tomography by -0.3+/-6.6 days, those of BDG measurement by 6.5+/-4.9 days, and those of ELISA by 2.8+/-4.1 days. Real-time PCR was sensitive for IPA diagnosis, and quantitation was accurate.

Adolescent↗

Angiogenesis in pancreatic carcinoma: thymidine phosphorylase expression in stromal cells and intratumoral microvessel density as independent predictors of overall and relapse-free survival.

BACKGROUND: Recently, the usefulness of intratumoral microvessel density (IMD) and expression of several angiogenic factors as prognostic indicators have been demonstrated in several human solid tumors. METHODS: One hundred four patients with pancreatic ductal adenocarcinoma were examined retrospectively. The investigated clinicopathologic and immunohistologic data included staining for vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP), basic fibroblast growth factor (bFGF), CD34 (for calculating IMD), p53, and Ki-67. RESULTS: Multivariate analysis for both overall and relapse-free survival revealed two independent variables, IMD and TP staining in stromal cells (TPs, P < 0.02). Whereas the frequency of hepatic metastasis was correlated significantly with cytoplasmic expression of TP or bFGF in tumor cells (TPc, bFGFc), IMD, and p53 status, local recurrence was significantly more common in patients with positive staining for TPs, bFGF in stromal cells (bFGFs), and for the pM category (P < 0.05). TPc, bFGFc, VEGF, and p53 expression correlated with IMD (P < 0.01), although TPs and bFGFs expression did not. VEGF and IMD status correlated with p53 expression (P < 0.001), although TP, bFGF, and Ki-67 status did not. CONCLUSIONS: TPs expression and IMD were revealed to be valuable tools for predicting overall and relapse-free survival in patients with pancreatic adenocarcinoma. Whereas TPc and bFGFc are likely to participate in hepatic metastasis by means of their angiogenic properties, TPs and bFGFs may be related to local tumor progression. Angiogenesis in human pancreatic carcinoma may be dependent on VEGF, TP, and bFGF. p53 abnormality is likely to take part in VEGF-related angiogenesis.

Adenocarcinoma↗

Temporal and spatial distribution of Fos protein in the lumbar spinal dorsal horn neurons in the rat with chronic constriction injury to the sciatic nerve.

The temporal and spatial expression pattern of Fos protein in spinal dorsal horn neurons was examined by immunohistochemistry in rats with chronic constriction injury (CCI) to the sciatic nerve. In normal animals, a few Fos-immunoreactive (-IR) neurons were detected in the dorsal horn of the lumbar spinal cord. Following induction of CCI, a very large number of Fos-IR neurons appeared in the spinal dorsal horn, but a significant number of Fos-IR neurons were also observed in the contralateral dorsal horn where primary afferents of the injured sciatic nerve rarely project. Sham-operated animals also had a significant number of Fos-IR neurons in the dorsal horn bilaterally. The number of Fos-IR neurons reached its maximal level 1 day following placement of the ligatures (PO 1d). The ratio of the number of Fos-IR neurons in the ipsilateral dorsal horn to the contralateral dorsal horn, however, had its peak level 3 days following CCI (3.1-fold increase compared to the contralateral dorsal horn). The number of Fos-IR neurons in the dorsal horn gradually decreased, but increased again around PO 15d. On PO 30d, the number of Fos-IR neurons decreased and became comparable to that in normal animals. The present results indicate that the induction of Fos-IR neurons in the dorsal horn caused by CCI is biphasic and reaches its maximal level on PO 3d, near the time of hyperalgesia onset.

Animals↗

Inhibition by green tea catechins of metabolic activation of procarcinogens by human cytochrome P450.

Catechins, major polyphenol constituents of green tea, are potent chemopreventive agents against cancers caused by chemical carcinogens in rodents. The effects of four epicatechin derivatives, epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC) and epicatechin (EC), on the metabolic activation of benzo[a]pyrene (B[a]P), 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) and aflatoxin B(1) (AFB(1)) by human cytochrome P450 (CYP) were examined. B[a]P, PhIP and AFB(1) were activated by respective human CYP1A1, CYP1A2 and CYP3A4 expressed in the membrane fraction of genetically engineered Salmonella typhimurium (S. typhimurium) TA1538 cells harboring the human CYP and human NADPH-CYP reductase (OR), when the membrane fraction was added to S. typhimurium TA98. Galloylated catechins, ECG and EGCG inhibited the mutagenic activation potently, while EGC and EC showed relatively weak inhibitory effects. Catechins also inhibited the oxidations of typical substrates catalyzed by human CYPs, namely ethoxycoumarin O-deethylation by CYP1A1, ethoxyresorufin O-deethylation by CYP1A2 and midazolam 1'-hydroxylation by CYP3A4. The IC(50) values of catechins for the inhibition of human CYP were roughly the same as those seen in the mutagenic activation. EGCG inhibited other forms of human CYP such as CYP2A6, CYP2C19 and CYP2E1, indicating the non-specific inhibitory effects of EGCG toward human CYPs. Furthermore, EGCG inhibited human NADPH-cytochrome CYP reductase (OR) with a K(i) value of 2.5 microM. These results suggest that the inhibition of the enzyme activity of CYP is accounted for partially by the inhibition of OR.

Aflatoxin B1↗

Tight Asp-85--Thr-89 association during the pump switch of bacteriorhodopsin.

Unidirectional proton transport in bacteriorhodopsin is enforced by the switching machinery of the active site. Threonine 89 is located in this region, with its O--H group forming a hydrogen bond with Asp-85, the acceptor for proton transfer from the Schiff base of the retinal chromophore. Previous IR spectroscopy of [3-(18)O]threonine-labeled bacteriorhodopsin showed that the hydrogen bond of the O--D group of Thr-89 in D(2)O is strengthened in the K photocycle intermediate. Here, we show that the strength and orientation of this hydrogen bond remains unchanged in the L intermediate and through the M intermediate. Furthermore, a strong interaction between Asp-85 and the O--H (O--D) group of Thr-89 in M is indicated by a shift in the C==O stretching vibration of the former because of (18)O substitution in the latter. Thus, the strong hydrogen bond between Asp-85 and Thr-89 in K persists through M, contrary to structural models based on x-ray crystallography of the photocycle intermediates. We propose that, upon photoisomerization of the chromophore, Thr-89 forms a tight, persistent complex with one of the side-chain oxygens of Asp-85 and is thereby precluded from participating in the switching process. On the other hand, the loss of hydrogen bonding at the other oxygen of Asp-85 in M may be related to the switching event.

Aspartic Acid↗

Ral promotes anchorage-independent growth of a human fibrosarcoma, HT1080.

Ral has been shown to act downstream of Ras oncoprotein. However, the role of Ral in Ras-induced cellular transformation has not been fully understood. To test the involvement of Ral in Ras-induced anchorage-independent growth, we ectopically expressed Ral mutants in HT1080 cells, whose ability to grow in the absence of anchorage depends on the oncogenic mutation of N-ras. Expression of an activated mutant of Ral resulted in enhanced growth of HT1080 cells in soft agar, whereas a dominant-negative mutant of Ral inhibited their anchorage-independent growth. Moreover, the activated Ral mutant decreased the amount of p27(Kip1) in the absence of adhesion, while the dominant-negative mutant increased it. These results suggest that Ral is involved in the Ras-dependent anchorage-independent growth of HT1080 cells by regulating p27(Kip1).

Base Sequence↗