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Biomedical subjects

H Nagata

Publications and source records attributed to H Nagata.

At least 109 records · Page 6Linked to original sources

Medical students' perception of inpatients' anxiety, self-esteem, purpose-in-life and health locus of control as compared with nursing practitioners'.

Medical students (fourth-year: n = 67; fifth-year: n = 63) estimated inpatients' feelings of anxiety, self-esteem, purpose-in-life, and multidimensional health locus of control. Their ratings were compared both with the ratings given by the 121 inpatients themselves and with those given by nursing practitioners (nurses and nursing students). Findings showed that the medical students overestimated inpatients' anxiety, while they underestimated the inpatients' purpose-in-life and internal health locus of control. Hence they underestimated, as did the nursing practitioners, the inpatients' positive emotional states and their positive attitude toward their own lives. Fifth-year medical students, with clinical experience, rated the inpatients' score of chance health locus of control higher than did the fourth-year medical students, who had no clinical experience. These findings indicate that medical students, like nursing practitioners, are inclined to pay more attention to inpatients' weaknesses than to their strengths.

Analysis of Variance↗

Antioxidative action of flavonoids, quercetin and catechin, mediated by the activation of glutathione peroxidase.

Antioxidative action of flavonoids have been attracted attention of many investigators and a good deal of studies on it were reported. While their interests were mostly centered to the direct scavenging action of flavonoids against free radicals and active oxygen species, we expected that the interaction of flavonoids and intracellularly occurring antioxidative agents such as glutathione peroxidase (GSH-PO) could synergistically enhance their antioxidative activities. For this purpose, cultured rat hepatocytes (BL-9), which are highly expressing GSH-PO, were employed. One group of the cells were cultured with Se deficient media (Se(-) cells) to diminish the activity and the expression of GSH-PO protein and mRNA, and the other group was cultured with Se supplemented media (Se(+) cells). The oxidative cell damage was induced by the addition of H2O2 and two representative antioxidative flavonoids, quercetin and catechin, were added to the media to test their cytoprotective action. In Se(+) cells, the remarkable cytoprotective activity of those flavonoids were confirmed, whereas none of such activity was evidenced in Se(-) cells. It was proved that the intracellular antioxidative function of flavonoids requires the interaction with GSH-PO, at least in the cells expressing the enzyme. Interestingly, the flavonoid activated GSH-PO clearly, and its mechanism is discussed.

Animals↗

Clinical correlates of the presence of the Asp816Val c-kit mutation in the peripheral blood mononuclear cells of patients with mastocytosis.

BACKGROUND: The Asp816Val mutation in the catalytic domain of the c-kit receptor has been identified in patients with systemic mastocytosis. METHODS: To determine whether this mutation is associated with identifiable clinical patterns of disease and prognosis, a total of 65 patients with mastocytosis were screened for the presence of the Asp816Val mutation in peripheral blood mononuclear cells (PBMCs). RESULTS: By analysis of HinfI digestion products, the authors found that the overall prevalence of this mutation in the current patient series was 25%. The presence of the Asp816Val mutation in PBMCs was observed in 15 adults (of 16 Asp816Val mutation positive patients) and 1 infant, but not in any children with mastocytosis. Patients whose PBMCs were positive for this mutation (category II and a subset of category Ib mastocytosis patients) manifested a more severe disease pattern, with clinical features ranging in severity from early to advanced myelodysplastic or myeloproliferative syndromes. These patients more commonly had osteosclerotic bone involvement (a clinical feature primarily observed in mastocytosis patients with an associated hematologic disorder) as well as immunoglobulin dysregulation and peripheral blood abnormalities. Furthermore, pedigree analysis of three families provided evidence that the mutation was somatic. CONCLUSIONS: Twenty-five percent of all patients with mastocytosis had the Asp816Val mutation in PBMCs; 56% of these patients had evidence of a myelodysplastic or myeloproliferative syndrome, and 44% had been clinically placed in the indolent mastocytosis category, suggesting that the current classification scheme used to assign prognosis may be inadequate. Therefore, determination of the presence or absence of this mutation in PBMCs of mastocytosis patients offers a useful adjunct in determining the extent of workup and assigning prognosis in this complex and heterogeneous disease.

Adolescent↗

Mammalian cytosolic DnaJ homologues affect the hsp70 chaperone-substrate reaction cycle, but do not interact directly with nascent or newly synthesized proteins.

Members of the hsp70 family of molecular chaperones interact with and stabilize nascent polypeptides during synthesis and/or translocation into organelles. The bacterial hsp70 homologue DnaK requires the DnaJ cofactor for its reaction cycle with polypeptide substrates. DnaJ stimulates the ATPase activity of the DnaK chaperone and thereby is thought to regulate the affinity of DnaK for its protein target. Herein we have analyzed some of the biochemical properties of two mammalian cytosolic DnaJ homologues, the hdj-1 and hdj-2 proteins. We were particularly interested in examining the proposal that DnaJ homologues are the first molecular chaperones to interact directly with nascent polypeptides. Nascent/newly synthesized proteins, nascent polypeptides released from the ribosome by puromycin, or polypeptides misfolded as a result of incorporation of an amino acid analogue were not found in complexes with either of the two HeLa cell DnaJ homologues. We still were unable to demonstrate any interactions between hdj-1p and nascent/newly synthesized proteins even after chemical cross-linking. We did find that hdj-1p, like bacterial DnaJ, stimulated the ATPase activity of hsp70. Stable complex formation between hsp70 and an unfolded polypeptide substrate in vitro was found to be reduced in the presence of hdj-1p and ATP. Thus, while hdj-1p likely does function as a cofactor for the hsp70 chaperone, having effects on hsp70's ATPase activity and conformation/oligomeric structure and the stability of hsp70-substrate complexes, it was not observed to interact directly with nascent/newly synthesized proteins. Rather, hdj-1p likely serves a regulatory role, governing the reaction cycle of hsp70 with polypeptide substrates.

Bacterial Proteins↗

Application of logistic growth model to pharmacodynamic analysis of in vitro bactericidal kinetics.

A new pharmacodynamic model for the analysis of in vitro bactericidal kinetics was developed based on the logistic growth model, with the bacterial phases divided into two compartments. The model equations are expressed as nonlinear simultaneous differential equations, and the Runge-Kutta-Gill method was adopted to numerically solve the equations in both the simulation and the least squares curve-fitting procedures. The model can describe the initial killing and the regrowth phases and can explain the nonlinear dependence of the killing rate on the drug concentration. The model can also explain the plateau in the bacterial growth curve that is often observed in in vitro experiments. The model was applied to analysis of the in vitro time-killing data of beta-lactam antibiotics, S-4661, meropenem, imipenem, cefpirome, and ceftazidim against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The results of curve-fitting using the least squares program MULTI (Runge) showed good fits for all types of drugs and bacteria. The relationship between the characteristics of the drug-bacteria interactions and the estimated pharmacodynamic parameters is discussed.

Anti-Bacterial Agents↗

Elevated expression of the proto-oncogene c-kit in patients with mastocytosis.

The stem cell factor (SCF)c-kit receptor interaction plays a critical role in the development and survival of mast cells. Several studies have also associated c-kit receptor mutations with the human diseases, mastocytosis and piebaldism. Overexpression of c-kit has been reported to be associated with myeloproliferative disorders and myelodysplastic syndromes. Using peripheral blood mononuclear cells (PBMCs) from 11 patients with indolent mastocytosis (category I), mastocytosis with an associated hematologic disorder (category II), or aggressive mastocytosis (category III); a patient with CMML unassociated with mastocytosis, and PBMCs from 13 normal subjects, we examined the level of expression of c-kit mRNA along with other c-kit isoforms to determine if overexpression of the c-kit receptor was associated with mastocytosis. Using quantitative competitive PCR, c-kit mRNA levels on average were found to be statistically elevated in the five patients with mastocytosis with an associated hematologic disorder and in the patient with aggressive mastocytosis as compared with controls, but not elevated in patients with indolent mastocytosis. The relative mRNA expression for the two c-kit isoforms was not significantly different in the mastocytosis patients compared with controls. This demonstration of the overexpression of c-kit mRNA in mastocytosis, and particularly those patients with clinical evidence of myelodysplastic syndrome, adds evidence to support the conclusion that mastocytosis, at least in some patients, is a feature of myelodysplasia; and suggests that determination of c-kit mRNA expression in PBMCs may provide an additional approach to assessing prognosis.

Adult↗

Analysis of long-term results of our combination therapy for squamous cell cancer of the maxillary sinus.

Seventy-four patients between 1971 and 1982 in Period I and 32 patients between 1982 and 1987 in Period II with maxillary sinus squamous cell cancer were treated by combination therapy consisting of preoperative LINAC X-ray irradiation with 5-flourouracil intra-arterial chemotherapy followed by maxillectomy and primary reconstruction. In Period II, 21 patients received preoperative cisplatinum (CPPP) microcapsule chemoembolization and pepleomycin (PEP) i.m. and or postoperative CDDP i.v. with PEP i.m. in addition to the combination therapy administered in Period I depending on systemic conditions, tumor stage and histopathological type. Five and 10-year crude survival rates were 68.9% and 55.4%, respectively, for Period I and 71.9% and 56.3% for Period II, with no significant difference between the two trials. In 21 selected patients in Period II, who had additional chemotherapy with preoperative CDDP chemoembolization and/or postoperative i.v. infusion of CDDP with pepleomycin i.m., 5 and 10-year survival rates were 85.7% and 61.9%, respectively.

Antineoplastic Agents↗

Analysis of factors affecting long-term treatment results of adenoid cystic carcinoma of the nose and paranasal sinuses.

At Akita University Hospital (from 1971 to 1987) and at Chiba University Hospital (from 1983 to 1988), 17 patients with adenoid cystic carcinoma of the nose and paranasal sinuses were treated by en bloc tumor resection followed by primary reconstruction of the maxilla. Pre- and postoperative radiation was combined in 5 and 6 patients, respectively. Ten-year cancer-free survival rates were 59.3% in the 12 patients with maxillary sinus tumors and 50% in the 4 patients with nasal tumors. One patient with a sphenoid sinus tumor died within 5 years. Ten-year cancer-free survival was affected markedly by grade of tumor extension. Among T1N0M0 and T2N0M0 patients (of which there were 1 and 7, respectively), only 1 died of unrelated causes, and 6 patients survived cancer-free for more than 10 years. However, 4 of the 6 T3N0M0 patients died, and the cause of death was distant metastasis in 2, intracranial tumor extension in 1, and unrelated causes in 1. All 3 T4N0M0 patients died, 2 due to intracranial tumor extension and 1 of unrelated causes. The cause of death was distant metastasis in 3, local recurrence in 3, 2 of whom had intracranial tumor extension, and unrelated causes in 2. Prevention of distant metastasis and intracranial tumor extension was considered to be crucial for improving treatment results after en bloc tumor resection. Preoperative radiation was thought to decrease incidence of distant metastasis. In 5 patients who had preoperative radiation. 4 survived cancer-free for more than 10 years, and only 1 patient died of unrelated cause. However. of the 6 patients who had postoperative radiation, 2 died of distant metastasis and another 2 died of intracranial tumor extension. Of the 6 patients who did not have radiation therapy, the causes of death were local recurrence in 1, distant metastasis in 1 and unrelated causes in 1. Preoperative radiation in 5 patients showed histopathologically moderate or marked degeneration and necrosis of tumors in all patients. Although the number of patients in this study is too small to allow statistical analysis of the data, our present modality of treatment for adenoid cystic carcinoma of the nose and paranasal sinuses is routine combination of preoperative full dose radiation, en bloc tumor resection and primary reconstruction, including en bloc resection of the cranial base in selected T4 patients.

Antineoplastic Agents↗

Enhanced expression of inducible nitric oxide synthase in chronic gastritis with intestinal metaplasia.

Nitric oxide produced by inducible nitric oxide synthase (iNOS) has been claimed to be involved in gastritis; however, its characteristics are largely unknown. We assessed (1) iNOS expression in the human gastric mucosa in chronic gastritis and (2) the cytokines associated with iNOS expression. Gastric biopsy specimens were obtained from patients with chronic gastritis. Total RNA was isolated and reverse transcription-polymerase chain reaction (PCR) was performed semiquantitatively using specific primer sets for iNOS, interleukin (IL)-1beta, IL-8, IL-6, interferon-y, tumor necrosis factor-alpha (TNF-alpha), TNF receptors, IL-6 receptors, and sucrase, respectively. Helicobacter pylori infection was examined by the PCR assay. Reverse transcription-PCR analysis showed that expression of iNOS was detected in 10 of 23 samples. Expression of iNOS mRNA was closely correlated with expression of TNF-alpha and was observed frequently in subjects with intestinal metaplasia. The Helicobacter pylori gene was detected by PCR assay in all iNOS-positive cases. These results indicate that iNOS is predominantly expressed in the gastric mucosa with intestinal metaplasia and H. pylori infection. TNF-alpha is thought to be an important cytokine associated with iNOS expression.

Adult↗

A new operation for producing disease-suppressive compost from grass clippings

This study evaluated the use of grass clippings discharged from golf courses as the raw material for production of a suppressive compost to control Rhizoctonia large-patch disease in mascarene grass. Bacillus subtilis N4, a mesophilic bacterium with suppressive effects on the pathogenic fungus Rhizoctonia solani AG2-2, was used as an inoculum in a procedure developed with the aim of controlling composting temperatures and inoculation timing. The population density of mesophilic bacteria in the raw material was reduced to around 5 log10 CFU/g (dry weight) of composting material in the self-heating reaction at the initial stage of composting by maintaining a temperature of 80 degreesC for 1 day. The inoculum was applied immediately, and the composting material was maintained at 40 degreesC for 3 days. This served both to highly concentrate the suppressive bacterium and to achieve sporulation. The temperature was then raised to 60 degreesC and maintained, enabling hygienic, high-speed composting while maintaining the population density of the suppressive bacterium as high as 8 log10 CFU/g (dry weight) in the compost. The suppressiveness of compost made in this way was confirmed in a turf grass disease prevention assay.

Journal Article↗

Immunohistochemical study of E-cadherin and ZO-1 in allergic nasal epithelium of the guinea pig.

Nasal epithelial damage during allergic inflammation was studied by observing the distribution of cell adhesion molecule E-cadherin and tight junction (zonula occludens) cell-cell contact associated protein ZO-1. The guinea pig model of nasal allergy, sensitized with intraperitoneally administered ovalbumin (OA) and subsequently challenged with OA intranasally, was used. In control epithelium, E-cadherin immunoreactivity was detected continuously along neighboring epithelial cell borders. ZO-1 spot-like immunoreactivity was detected in the apicolateral portion of epithelial cells corresponding to the tight junction (TJ) position, but no changes in immunoreactivity were found between control and challenged epithelia. In the challenged epithelium of sensitized animals, marked infiltration of eosinophils and structural changes, such as widening of the intercellular spaces and detachment of adjacent epithelial cells, were observed concurrently. In addition, spots negative for E-cadherin immunoreactivity were noted in the epithelium, associated with the extracellular deposition of eosinophil granule proteins. Immunoelectron microscopy revealed a decrease or disappearance of E-cadherin immunoreactivity, which took place not only in regions where intercellular spaces were wide and adjacent epithelial cells were detached, but also at the point of contact between infiltrating eosinophils and epithelial cells. Approximately 87% of eosinophils observed in the challenged epithelium were associated with such loss of E-cadherin immunoreactivity. These results suggest that the intimate epithelial cell contact mediated by E-cadherin is loosened as a consequence of eosinophil infiltration, which may trigger the initial step of subsequent epithelial destruction in allergic states.

Animals↗

A remote collaboration system for telemedicine using the Internet.

We have developed a still-image telemedicine system for the Internet. It was implemented with the Java programming language and enables remote collaboration between two or more client computers located anywhere on the Internet. Each client requires only a PC or workstation and a popular Internet browser--no special hardware or software is required. We carried out both local-area and wide-area tests of the system. On a local network, JPEG images at a resolution of 640 x 480 pixels took 2-5 s to display on four different clients (PCs or workstations); at 1000 x 1000 pixels, the images took 10-65 s. We also tested the system between two universities in Japan, one in Italy and one in the USA, using the Internet for communications. Images required 4-20 s for display. The exchange of remote collaboration commands between the four locations was good and the maximum lag in mouse pointer movement was less than 1 s. The system has the potential to solve three problems of conventional telemedicine systems: their cost, the need for high-bandwidth telecommunication and the low compatibility between them.

Computer Communication Networks↗

Nursing practitioners' perception of inpatients' anxiety, self-esteem, purpose-in-life and health locus of control.

This study explored how nursing practitioners perceived inpatients' anxiety, self-esteem, purpose-in-life and multidimensional health locus of control. Seventy-three nurses, 60 third-year and 70 first-year nursing students, and 61 control students not majoring in nursing science estimated how inpatients rated these four psychological states. Their ratings were compared with those given by 121 inpatients. Findings showed that the nursing practitioners, as well as the control participants, overestimated inpatients' anxiety, while they underestimated their self-esteem and purpose-in-life. The inpatients' scores for internal locus of control were greater than their scores for the two types of external locus of control (powerful others and chance), and were also greater than the scores given by the nursing practitioners in estimating the patients' perception of internal locus of control. The findings indicate that inpatients have a more positive attitude toward themselves and their own lives, and hence much better mental health, than the nursing practitioners estimate they do.

Adult↗

Decrease in gamma-actin expression, disruption of actin microfilaments and alterations in cell adhesion systems associated with acquisition of metastatic capacity in human salivary gland adenocarcinoma cell clones.

In order to clarify how cytoskeletons and adhesion systems change through acquisition of metastatic capacity in a cancer cell, we examined the expressions of beta- and gamma-actin, the morphology of actin microfilaments and focal contacts, and also the expression of vinculin in a salivary gland adenocarcinoma cell clone cl-1, which acquired metastatic capacity, in comparison with its original clone HSGc lacking metastatic ability. Two-dimensional gel electrophoresis of Triton-insoluble fractions and combined Western blot analysis by immunostaining with anti actin-isoform antibodies showed that the expression of gamma-actin was somewhat lower than that of beta-actin in HSGc, and cl-1 expressed a comparable amount of beta-actin to HSGc, whereas gamma-actin expression by cl-1 was far less than that by HSGc. Northern blot analysis demonstrated that there was little difference in the level of beta-actin mRNA between HSGc and cl-1, while the level of gamma-actin was markedly decreased in cl-1 as compared with HSGc. In terms of morphology, cl-1 cells showed disruption of actin microfilaments and a decrease in the size and number of focal contacts on the cell surface. Furthermore, cl-1 showed decreased expression of vinculin, which became obscured even at the end of actin microfilaments. These results demonstrated that a decrease in gamma-actin, disruption of actin microfilaments, and suppression of focal contacts as well as vinculin take place in the transformation from a non-metastatic condition to a metastatic one in the human salivary gland adenocarcinoma cell clones. Thus, it was strongly suggested that these changes contribute to a decrease in cell adhesiveness and an increase in cell motility, which is probably a major cause for acquisition of metastatic potential.

Actin Cytoskeleton↗

World wide microscope: new concept of internet telepathology microscope and implementation of the prototype.

We defined a new concept of microscope system for telepathology, named World Wide Microscope (WWM), and implemented its prototype. WWM is constructed by the following three units; (1) microscope unit, (2) control unit, and (3) internet unit. The microscope unit is a conventional light microscope equipped with a motor drive X-Y stage and an objective lens revolver, auto focus and auto iris functions, and a CCD camera. The internet unit is a World Wide Web homepage in which a Java applet and a communication server are installed. The applet is implemented several methods that realize to make a PC client on the Internet as a telepathology terminal. The control unit relays request commands generated from the applet to the microscope unit, and captures the microscopic images. We think WWM will probably become the all round telepathology tool of the next generation.

Evaluation Studies as Topic↗

Clinical features of ovarian cancer in Japanese women with germ-line mutations of BRCA1.

We analyzed the clinical features of 25 ovarian cancer patients who were associated with germ-line mutations of BRCA1 from four site-specific ovarian cancer families and seven breast-ovarian cancer families in Japan. The average age at diagnosis was 51.1 years (range, 38-77 years). Histological examination revealed 24 serous cyst adenocarcinomas in 25 patients. In 23 patients with clear clinical records, 3 patients had stage I disease, 17 had stage III disease, and 3 had stage IV disease. Thirteen patients with stage III disease who were treated with cisplatin-containing chemotherapy following tumor reduction surgery showed more favorable outcomes in both the survival rate and disease-free intervals, compared with age- and treatment course-matched controls (5-year survival rate, 0.786 versus 0.303; median disease-free interval, 91.43 versus 40.92 months; P < 0.05 for both, by logarithmic rank test). Our statistical model for the inheritance of susceptibility to ovarian cancer was derived from the analysis of 26 patients and 19 healthy carriers of 12 families. The expected lifetime risk of ovarian cancer is about 80% for women with mutations of BRCA1. These results suggest that the clinical outcome of ovarian cancer with germ-line mutations of BRCA1 appears to be more favorable than that with sporadic cases and that the disease penetrance among pedigrees with germ-line mutations of the BRCA1 gene is substantially high.

Adult↗