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Biomedical subjects

T Sawada

Publications and source records attributed to T Sawada.

At least 235 records · Page 13Linked to original sources

Disseminated retinoblastoma successfully treated with myeloablative chemotherapy--implication for molecular detection of minimal residual disease.

A useful marker for detecting minimal residual disease (MRD) has not been established yet in retinoblastoma. We assessed neuroendocrine protein gene product 9.5 (PGP9.5) expression, one of the markers for detecting MRD in neuroblastoma, in a patient with disseminated retinoblastoma. A 3-year-old boy with disseminated retinoblastoma in multiple bones and marrow was referred to our hospital. He received intensive treatment and has maintained CR for 48 months following myeloablative chemotherapy with hematopoietic stem cell transplantation (SCT). PGP9.5 expression was serially assessed by RT-PCR in peripheral blood mononuclear cells (PBMC), bone marrow cells (BMC) and mobilized peripheral blood stem cells (PBSC). Initially, his BMC consisted of 96% tumor cells which were proved to express PGP9.5 by RT-PCR. Moreover, PBMC were found to be positive for PGP9.5 indicating the presence of tumor cells in the peripheral blood. After intensive chemotherapy, PGP9.5 expression became negative in both PBMC and BMC. Prior to SCT, PBSC and BMC transplants were confirmed negative for PGP9.5 expression. It is suggested that PGP9.5 expression is a useful marker for evaluating therapeutic effects as well as detecting MRD in retinoblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Serum hepatocyte growth factor levels in Henoch-Schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) is the most common form of vasculitis in children. The potential role of hepatocyte growth factor (HGF) in acute immune-mediated vasculitis has not been elucidated. METHODS: Serum HGF levels were determined in patients with HSP. RESULTS: In patients with acute-phase HSP, mean (+/- SD) serum HGF levels were 0.32 +/- 0.14 ng/mL and were significantly higher than those in the control group (0.11 +/- 0.10 ng/mL). This elevation of serum HGF levels recovered to control levels in parallel with improvement of the clinical symptoms. CONCLUSIONS: It is suggested that elevation of serum HGF levels in patients with acute-phase HSP may reflect endothelial cell damage or dysfunction in HSP.

Acute Disease↗

Chimeric cytokine receptor can transduce expansion signals in interleukin 6 receptor alpha (IL-6Ralpha)-, IL-11Ralpha-, and gp130-low to -negative primitive hematopoietic progenitors.

We generated transgenic mice expressing chimeric receptors, which comprise extracellular domains of the human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor and transmembrane and cytoplasmic domains of the mouse leukemia inhibitory factor receptor. In suspension cultures of lineage-negative (Lin(-)), 5-fluorouracil-resistant bone marrow cells of the transgenic mice, a combination of hGM-CSF and stem cell factor (SCF) induced exponential expansions of mixed colony-forming unit. The combination of hGM-CSF and SCF was effective on enriched, Lin(-)Sca-1(+)c-kit(+) progenitors and increased either mixed colony-forming unit or cobblestone area-forming cells. In case of stimulation with hGM-CSF and SCF, interleukin-6 (IL-6) and SCF, or IL-11 and SCF, the most efficient expansion was achieved with hGM-CSF and SCF. When Lin(-)Sca-1(+)c-kit(+)CD34(-) further enriched progenitors were clone sorted and individually incubated in the presence of SCF, hGM-CSF stimulated a larger number of cells than did IL-6, IL-6 and soluble IL-6 receptor (IL-6R), or IL-11. These data suggest the presence of IL-6Ralpha-, IL-11Ralpha-, and gp130-low to -negative primitive hematopoietic progenitors. Such primitive progenitors are equipped with signal transduction molecules and can expand when these chimeric receptors are genetically introduced into the cells and stimulated with hGM-CSF in the presence of SCF.

Animals↗

Adhesion preventive effect of hyaluronic acid after intraperitoneal surgery in mice.

Prevention of intraperitoneal adhesion after gynaecological surgery is essential for maintaining postoperative fertility. In this study, the adhesion prevention effect was examined of a hyaluronic acid (HA) solution obtained from the fermentation method and having a molecular weight of 1.9x10(6) with high viscosity. Laparotomy was conducted on female mice 7 weeks old, whose menstrual periods were synchronized by pregnant mare serum gonadotrophin (PMSG) to injure the uterine horn surface. Intraperitoneal adhesions were favourably formed in 91.7% of cases induced with iodine abrasion, compared with 50% induced by electrosurgery. Intraperitoneal administration of HA was evaluated for its effect on the prevention of adhesions made by iodine abrasion. Adhesion prevention effects of HA were observed at concentrations of 0.3, 0.5, 0.75 and 1.0%, among which the most pronounced effect was with the use of a 0.3% solution (92.3% of cases). Compared with the control group adhesion score of 2.0 +/- 0. 8, significant decreases in adhesion scores were observed at all concentrations. HA with a molecular weight of 1.9x10(6) was recognized to have a definitive prevention effect on postoperative adhesions in mice after laparotomy and is considered to be a prospective material for future clinical use.

Animals↗

Carnitine import to isolated hepatocytes and synthesis are accelerated in pivalate-treated rats.

To investigate the effect of pivalate on carnitine import and carnitine synthesis in the liver, we measured carnitine uptake in isolated rat hepatocytes with L-[(14)C] carnitine and concentrations of free carnitine, gamma-butyrobetaine and acylcarnitines using tandem mass spectrometry. Hepatocytes from rats treated with 20 mmol/L of pivalate for 4 wk had greater L-[(14)C] carnitine uptake than those of unsupplemented rats after 5, 10, 30 and 90 min. Addition of 1 mmol/L of pivalate or 1 mmol/L of pivaloylcarnitine to control cell suspensions did not affect L-[(14)C] carnitine uptake. The K(m) values for L-[(14)C] carnitine uptake for pivalate-treated rats were significantly lower than control (2.9 +/- 0.7 mmol/L for pivalate-treated rats, 6.2 +/- 1.1 mmol/L for controls). The concentration of free carnitine was not reduced in the liver of pivalate-treated rats, whereas the concentrations of acetylcarnitine and gamma-butyrobetaine were significantly lower than controls. In the heart and muscle the concentration of free carnitine was significantly lower and that of gamma-butyrobetaine was higher than controls. These results suggest that carnitine transport from plasma into the liver and synthesis in the liver are accelerated in rats with secondary carnitine deficiency induced by the administration of pivalate.

Animals↗

Ultrastructural verification of anchoring role of lamina fibroreticularis of dental basement membrane in odontogenesis.

In a previous study of the developing tooth a characteristic fibrillar layer associated with the basement membrane of the inner enamel epithelium was found to be a highly specialized lamina fibroreticularis of the basement membrane which is unusually rich in basotubules, 10 nm wide microfibril-like structures. In this study this layer was further examined in detail in the hope of ultrastructurally elucidating its role in odontogenesis. Tooth germs of the monkey (Macaca fuscata) were processed for thin section observations. Dental papilla cell processes were inserted into the lamina fibroreticularis and their surface was closely associated with numerous parallel basotubules. With high-resolution observations the space between the surface and nearest basotubules as well as the spaces between neighbouring basotubules were bridged by 1.5-3 nm wide filaments running perpendicular to the axis of basotubules. These results indicate that the processes of dental papilla cells are linked to groups of basotubules by means of 1.5-3 nm wide filaments. Immunoperoxidase staining showed the presence of fibronectin along basotubules as well as within the space between the process and basotubule. This result, together with the comparison of these filaments with microfibril-associated 1.2-3 nm wide fibronectin filaments and the reported abundance of fibronectin in the basement membrane area during odontogenesis, indicates that these 1.5-3 nm wide filaments are composed of fibronectin. After immunostaining for amyloid P component, done with the rat tissue because of the nature of an available antiserum, basotubules in the lamina fibroreticularis were positively stained, as has been shown in basotubules/microfibrils in other locations. Microfibrils function as anchoring rods by interlinking connective tissue components to one another and to the cells. Basotubules, thought to be basement membrane-incorporated microfibrils, in the lamina fibroreticularis in this study are also likely to function as an anchoring device to immobilize dental papilla cells along the basement membrane. Such an arrangement of mesenchymal cells is known to be crucial for the successful differentiation of odontoblasts in the developing tooth.

Animals↗

Preoperative clinical radioimmunodetection of pancreatic cancer by 111 In-labeled chimeric monoclonal antibody Nd2.

The present study was carried out with the purpose of evaluating the clinical usefulness of radioimmunodetection (RAID) with 111In-labeled murine/human chimeric monoclonal antibody, Nd2 (c-Nd2) in patients with pancreatic cancer. Nineteen patients suspected to have pancreatic cancer were administered intravenously 74 MBq/2 mg 111In-labeled c-Nd2 in 100 ml of saline containing 2% albumin over 30 min. A scintigram was obtained on the 3rd day after infusion by using single photon emission computed tomography (SPECT) imaging. Of the 14 patients finally diagnosed as having pancreatic cancer on the basis of surgical specimens or progress of disease, specific focal uptake at the site of the tumor was detected in 12 (true positive cases), representing a sensitivity of 85.7% (12/14), and liver metastasis was found in one case with metastasis. Of the 5 patients diagnosed with tumor-forming pancreatitis (TFP), 4 patients demonstrated true negative imaging, but one patient whose tumor demonstrated interesting findings in histology and immunostaining, showed false positive imaging. Of patients investigated for human anti-chimeric antibody (HACA) response, none showed HACA response, and no allergic reaction was seen in any of the patients administered c-Nd2. These results suggest that RAID with 11In-labeled c-Nd2 is useful for differential preoperative diagnosis between invasive pancreatic cancer and TFP.

Aged↗

Detection of borna disease virus-reactive antibodies from patients with psychiatric disorders and from horses by electrochemiluminescence immunoassay.

The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans. We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies. By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosis and 17 with leprosy, there was no positive case except one case each with alcohol addiction, AIDS, and dementia. Although 19 (1.36%) of 1,393 patients with various ocular diseases, 10 (1.09%) of 917 blood donors, and 3 (4.55%) of 66 multitransfused patients were seropositive for BDV-specific antigen, high levels of seroprevalence in schizophrenia patients and young patients (16 to 59 years old) with mood disorders were statistically significant. The immunoreactivity of seropositive sera could be verified for specificity by blocking with soluble p40 and/or p24 recombinant protein. Anti-p24 antibody was more frequent than p40 antibody in most cases, and in some psychotic patients antibody profiles showed only p40 antibody. Although serum positive for both p40 and p24 antibodies was not found in this study, the p40 ECLIA count in schizophrenia patients was higher than that of blood donors. Furthermore, we examined 90 sera from Japanese feral horses. Antibody profiles of control human samples are similar to that of naturally BDV-infected feral horses. We concluded that BDV infection was associated in some way with psychiatric disorders.

Age Distribution↗

Photothermal applications of lasers: study of fast and ultrafast photothermal phenomena at metal-liquid interfaces.

Recent studies on fast (<10 ns) and ultrafast (<10 ps) photothermal and photoacoustic phenomena occurring at solid-liquid interfaces are discussed, including related topics, with emphasis placed on interfaces between aqueous solutions and metals under electrochemical potential control. Details of transient reflecting grating measurements for metal-liquid interfaces are considered as they relate to mesoscopic interface structures and nano-environments. Dependencies of fast photothermal phenomena on the electrochemical potential and types of anions in the solutions are shown. Ultrafast photothermal phenomena observed by transient reflectivity measurements are considered in connection with interface femtochemistry and hot electron reactions. Technical progress in measuring fast and ultrafast photothermal phenomena is reviewed for solid-liquid interfaces, including colloidal solutions.

Journal Article↗

Serum hepatocyte growth factor levels in patients with renal diseases.

The serum levels of hepatocyte growth factor (HGF) were determined in patients with various renal diseases. In patients with acute-phase acute renal failure (ARF) and chronic tubulointerstitial nephritis (chronic TIN), the serum HGF levels were 0.55 +/- 0.24 and 0.44 +/- 0.37 ng/ml (mean +/- SD), respectively, and were significantly higher than that in the control group (0.12 +/- 0.12 ng/ml). The serum HGF level tended to be high also in patients with active-phase steroid-sensitive nephrotic syndrome (SSNS). The serum levels of HGF were not elevated in patients with IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), membranoproliferative glomerulonephritis (MPGN), poststreptococcal acute glomerulonephritis (PSAGN), unilateral renal atrophy, unilateral nephrectomy, or proximal tubular dysfunction. These observations suggest that glomerular disorders cause no apparent elevation of the serum HGF level, and that elevation of the serum HGF level may be associated with tubulointerstitial damage in renal diseases.

Adolescent↗

Long-term survivors of advanced neuroblastoma with MYCN amplification: A report of 19 patients surviving disease-free for more than 66 months.

PURPOSE: According to initial reports, stage 4 neuroblastoma patients with amplification of the MYCN proto-oncogene developed progressive disease within 8 months. The prognosis for such patients, however, should now be reevaluated in light of recent results achieved with up-to-date combination chemotherapy. PATIENTS AND METHODS: Patients with stage 3, 4, and 4S neuroblastoma and more than 10 copies of MYCN received induction chemotherapy, which from January 1985 to February 1991 consisted of regimen A(1 )(cyclophosphamide 1,200 mg/m(2) on day 1, vincristine 1.5 mg/m(2) on day 1, pirarubicin 40 mg/m(2) on day 3, and cisplatin 90 mg/m(2) on day 5) and from March 1991 to September 1993 consisted of regimen A(3 )(cyclophosphamide 1,200 mg/m(2) on days 1 and 2, pirarubicin 40 mg/m(2) on day 3, etoposide 100 mg/m(2) on days 1 through 5, and continuous infusion cisplatin 25 mg/m(2) on days 1 through 5). Most of these patients underwent radical surgery to remove the original tumor and local metastases, irradiation, and supralethal preconditioning regimens, followed by blood stem-cell transplantation (SCT). Data on the patients were collected in December 1998, and the factors contributing to disease-free survival were analyzed. RESULTS: During the study period, 66 patients with more than 10 copies of MYCN were treated. Five of nine patients with stage 3 disease, 13 of 55 with stage 4, and one of two with stage 4S survived for at least 66 months. It is interesting that all but one patient who survived for more than 66 months underwent SCT, in contrast with only five of 45 patients who died. CONCLUSION: Not all patients with advanced neuroblastoma who have more than 10 copies of MYCN will die. The requisites for survival in such patients seem to be intensive induction chemotherapy, effective surgery, irradiation, and the use of SCT.

Antineoplastic Combined Chemotherapy Protocols↗

Nasal nocardiosis in a calf.

Nasal nocardiosis was found in a female Japanese Black calf, 11 months of age. Macroscopically, the posterior half of the left nasal passage was completely obstructed by yellowish brown caseous substance and the mucosa was irregularly thickened. In the brain, a few soft brown foci were present in the olfactory bulb and frontal lobe. Microscopically, there were closely packed granulomas in the nasal cavity and brain. The lesions were characterized by a center of cellular debris surrounded by epithelioid macrophages, neutrophils, lymphocytes and multinucleated giant cells of the Langhans type. Special stains revealed the presence of a large number of filamentous branching gram-positive, partially acid-fast organisms in these epithelioid cells and giant cells, and in cellular debris.

Animals↗

Vascular and stromal changes in irradiated and recovering rat thymus.

To analyze the mechanisms responsible for thymocyte proliferation, maturation and migration in the thymus, the rat thymus just after, and recovering from irradiation was studied morphologically. The vascular structures of the rat thymus after a radiation dose of 6 Gy were found to be destroyed on day 3, but had recovered to almost normal by day 7, suggesting that the abrupt recovery of thymus structure after irradiation was due primarily to this change in vascular structure. Furthermore, the epithelial tissues in the thymic cortex appeared to contribute to this abrupt proliferation, and possibly to the abrupt maturation of thymocytes, while medullary epithelial tissues remained sparse and appeared inactive for a relatively long period. These findings are considered important for understanding the interrelationship between thymic epithelial cells and thymocytes with respect to thymocyte proliferation, maturation and migration.

Animals↗

Relationship between coronary blood flow velocity waveform and transmural distribution of myocardial blood flow in coronary artery.

It is important to know the transmural distribution of myocardial blood flow in assessing the severity of ischemia in coronary heart disease. We analyzed the relation between phasic waveform of epicardial coronary flow velocity with a Doppler flow probe in the left anterior descending artery in dogs and regional myocardial blood flow using a colored microsphere technique. Time-velocity integral in an average of 5 cardiac cycles was measured as an index of coronary blood flow during diastole (TVId) and systole (TVIs). The diastolic fraction of coronary blood flow (%DF) was defined as TVId/(TVId + TVIs). Myocardial specimens were divided into inner (subendocardial), middle, and outer (subepicardial) layers, and the inner layer to outer layer myocardial blood flow ratio (endo/epi ratio) was used as an index of transmural distribution of myocardial perfusion. The mean endo/epi ratio and the mean %DF decreased as the pressure gradient increased. There was a moderate but significant correlation (r = 0.57) between the endo/epi ratio and the %DF. In conclusion, analysis of the phasic pattern of coronary blood flow velocity provides some information about the transmural distribution of blood flow in the myocardium. The %DF may be a useful index for evaluating subendocardial ischemia.

Animals↗

Sex differences in susceptibility of ICR mice to oral infection with Corynebacterium kutscheri.

Sex difference in susceptibility to oral infection with Corynebacterium (C.) kutscheri was experimentally studied in ICR mice. Immature (4-week-old) and adult (14-week-old) mice were inoculated with two infecting doses of C. kutscheri, and necropsied for bacteriological and serological survey 4 weeks after the bacterial infection. No macroscopic lesions at necropsy were demonstrated, except for one adult male given 10(9) bacteria. In immature mice, C. Kutscheri isolated from the oral cavity and cecum with FNC agar, were recovered in only 40.0% of female mice but in 90.0% of male mice given 10(6) bacteria (p < 0.05), and in only 55.6% of female mice but in 80.0% male mice given 10(8) bacteria. In adult mice given 10(9) bacteria, the organism were recovered in only 45.5% of female mice but in 90.9% of male mice (p < 0.05), furthermore, the mean number of organisms in the cecum of male mice harboring the organism was significantly higher than that in females (p < 0.01). Castration caused an increase in host resistance in adult male mice. These results indicated that ICR male mice were more susceptible than females, in terms of bacterial colonization in the cecum and the oral cavity, to oral infection with C. kutscheri.

Aging↗

Changes in neoplastic cell features and sensitivity to mitotane during mitotane-induced remission in a patient with recurrent, metastatic adrenocortical carcinoma.

A 58-year-old man had adrenocortical carcinoma in the right adrenal gland. The tumour secreted excessive cortisol and dehydroepiandrosterone-sulphate (DHEA-S), and had invaded the right hepatic lobe and vena cava. Eleven months after surgical tumour resection, the serum DHEA-S levels again increased. Local tumour recurrence and a metastasis was found in the lung. Eleven months after surgery chemotherapy with mitotane (o,p'-DDD) was initiated. Twelve weeks of mitotane reduced serum DHEA-S levels and caused these tumours to disappear. The patient was then treated with low-dose mitotane (1.5-2.0 g/day) for 2 years. Serum levels of mitotane remained at less than 10 microg/ml. Although such low serum levels of mitotane and delayed initiation of mitotane after surgery have been proposed to weaken the antineoplastic effect of mitotane, the patient had a remission for 2 years. However, there was then local re-recurrence with an increase in serum DHEA-S and death 4 months later. The histological features of neoplastic cells were quite different comparing tumour resected at surgery and tumour at autopsy. The latter had more frequent mitotic nuclei. This tumour was initially sensitive to mitotane, but later became insensitive.

Adrenal Cortex Neoplasms↗

The influence of craniofacial form on bite force and EMG activity of masticatory muscles. VIII-1. Bite force of complete denture wearers.

Today, Japan as a society is aging. The average life expectancy of Japanese people is approximately 80 years. One result of this is that preservation of masticatory functions in elderly people has become increasingly important from the viewpoint of quality of life. In the future, the use of dentures in facilitating masticatory functions as a substitute for teeth that are lost during the aging process will assume greater significance. Accordingly, appropriate evaluation and judgment of complete dentures for edentate jaws is crucial. This study was designed to elucidate the effects of the craniofacial form in complete denture wearers on the mode of activity of gnathic functions. First, subjects wearing complete dentures in both the upper and lower jaws were instructed to carry out vertical clenching, and bite force direction was determined. These data were then related to the subject's craniofacial morphology. These results suggest that the bite force direction in complete denture wearers is not affected by gender differences, but is closely associated with lateral craniofacial morphology, and that appropriate setting of occlusal plane and the occluded vertical dimension is extremely important in the preparation of complete dentures.

Aged↗