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Biomedical subjects

J Hashimoto

Publications and source records attributed to J Hashimoto.

At least 109 records · Page 6Linked to original sources

[Immunotherapy of malignant lymphoma with interleukin-2 and sizofiran--a basic study on EL-4 lymphoma-transplanted mice].

The anti-tumor effects of recombinant human interleukin-2 (rIL-2) and sizofiran (SPG) were evaluated individually and in combination in C57BL/6 mice intraperitoneally inoculated with EL-4 lymphoma. The anti-tumor effects were evaluated by analysis of the intraperitoneal cell population in Giemsa-stained specimens, surface marker analysis of peritoneal exudative cells with flow cytometry, cytotoxic assay of cells against autologous tumor and Yac-1 lymphoma and a negative selection method, to identify the anti-tumor effector cells showing cytotoxic activity. The administration of SPG and/or rIL-2 reduced the lymphoma cells and proliferating lymphocytes, resulting in a decreased tumor/lymphocyte ratio in the order:control mice > SPG-treated mice > rIL-2-treated mice > rIL-2 plus SPG-treated mice. On day 5 after tumor inoculation, elevations in the number of L3T4+, Lyt2+, asialo GM1+ or Mac-1+ were demonstrated in the order:control mice < SPG-treated mice < rIL-2-treated mice < rIL -2 plus SPG-treated mice. The cytotoxic activity of peritoneal exudative cells against autologous tumor and the NK (natural killer) activity were increased in the same order. The anti-tumor effector cells which showed cytotoxic activity against autologous tumor cells were cytotoxic T lymphocytes, NK cells and cytotoxic macrophages. In the mice treated with SPG and rIL-2 plus SPG, especially, cytotoxic macrophages were shown to be the main anti-tumor effector cells. On day 10 after the inoculation, both a marked reduction in Lyt2+ lymphocytes and an elevation of L3T4+ lymphocytes were observed in all groups of mice. NK cells and cytotoxic macrophages were thought to be the main effector cells against autologous tumor, but their cytotoxic activities were lower than those examined on day 5. It was demonstrated that the administration of SPG and/or rIL-2 to the EL-4 lymphoma-bearing mice activated immune response cells in the peritoneal cavity such as T lymphocytes, NK cells or macrophages, which caused a reduction in lymphoma cells. The combination rIL-2 and SPG therapy was shown to activate the anti-tumor immune response at the tumor site more effectively than when either agent was administered alone.

Animals↗

[Exercise and rest myocardial scintigraphy with 201TlCl/99mTc-MIBI dual energy acquisition using triple-energy window scatter correction].

We carried out dual 201Tl/99mTc-MIBI imaging, to reduce the time required for exercise myocardial scintigraphy. We investigated 4 different protocols. In protocol (A), Tl was injected at rest followed by the injection of MIBI at peak exercise. Dual SPECT images were obtained by 201Tl/99mTc simultaneous acquisition. Protocol (B) means reverse either, in which MIBI was injected at rest followed by the administration of Tl at peak exercise. In protocol (C), exercise was performed first with MIBI-injection, and then Tl was injected at rest after one hour later. Simultaneous acquisition was also performed. In protocol (D), after the rest Tl-imaging, MIBI was injected at peak exercise, and then the MIBI-imaging was done. In protocol (A), (B) and (C), simultaneous acquisition was performed using TEW (Triple-Energy Window) scatter correction. Thanks to using dual isotopes, all procedures could be completed within 1-2 hours, which was much shorter than the conventional myocardial perfusion imaging. Scatter correction was useful for accurate diagnoses, when the simultaneous imaging is performed.

Exercise Test↗

[Quantitative evaluation of liver function with 99mTc-GSA scintigraphy using extraction index].

Extraction index (EI5) was introduced to evaluate liver function quantitatively with 99mTc-GSA (GSA) scintigraphy, and it was compared with conventional indices; receptor index (LHL15) and clearance index (HH15). EI5 is expressed as following equation: EI5 = (L5 - L3)/(H3 + H5) * PH/PL where L3, L5: counts at 3 or 5 minutes after the injection in the liver ROI, respectively, H3, H5: counts at 3 or 5 minutes in the heart ROI, respectively; PL, PH: numbers of pixels in the liver- and heart-ROI, respectively. We performed GSA scintigraphy in 40 patients with liver dysfunction and calculated values of the indices. Good correlations were observed between EI5 and liver function tests. Correlation coefficients were almost equal to or higher than those between conventional parameters and liver functional tests. EI5 was thought to be a practical index, and it could be calculated in a short time without aid of computer. Evaluation of local liver function may be possible, because EI5 was corrected with numbers of pixels in the liver- and heart-ROI; which was not considered in the conventional parameters.

Adult↗

[Phase I clinical study for 111In-DTPA-IgG].

A phase I study was performed in three health volunteers to evaluate the safety and biodistribution of 111In-DTPA-IgG, a newly developed imaging agent for inflammation/infection. No adverse effect was observed. There were no clinically significant changes in blood chemistry, hematology, and urinalysis parameters, physical examinations or vital signs. 111In-DTPA-IgG in blood exhibited a biexponential disappearance, consisting of a fast component (t1/2 alpha) ranging from 5.72 to 8.51 hours, and a slow component (t1/2 beta) ranging from 34.0 to 35.5 hours. Twelve percent of the injected dose was eliminated in the urine within 72 hours. Dosimetry estimates indicated that up to 80 MBq of 111In-DTPA-IgG can be safely administered to subjects without exceeding generally accepted absorbed dose for other scintigraphic procedures for inflammation/infection. The organs receiving the highest absorbed dose was the liver followed by the kidneys, heart, and lungs. Each of these organs received less than 40 mGy per 80 MBq administered. The safety data and dosimetry estimates indicated that it is safe to proceed with phase II studies with a 40-80 MBq dose of 111In-DTPA-IgG.

Adult↗

[A case of liposarcoma originating from the chest wall].

A 76-year-old woman with a growing tumor of the anterior chest wall was admitted to our hospital. This patient was diagnosed as having the malignant pleomorphic tumor using the needle biopsy and operated on. The operative procedure included wide resection of the tumor, associated excision of the major and minor pectoris muscle. The tumor size measured 10.5 x 5.8 x 5.5 cm and weighed 580 g. Histopathologically the tumor was confirmed to be poorly differentiated liposarcoma. While there was no invasion to the surrounding tissue, the local recurrence and metastasis wasn't confirmed for the past 7 months after the surgery. The major anatomic distribution of liposarcomas were retroperitoneum and lower extremities, and liposarcomas originating from the chest wall having been reported are only 7 cases of in Japan.

Aged↗

Destructive processes of salivary gland parenchyma and development of epimyoepithelial islands assessed by immunohistochemistry.

Thirteen salivary gland lesions showing destructive features and development of epimyoepithelial islands were studied using a panel of monoclonal antibodies to B cell (Dako, CD20 L26), T cell (UCHL1), macrophage histiocyte MH cell (Dako, MAC387), cytokeratin PKK1, KL1, K8.12, actin, vimentin and Von Willebrand factor (v WF). B cells were distributed closely in some limited areas and T cells were scattered throughout the lesion. MH cells were located particularly in the periductal tissue as well as in ducts and acini. Actin staining was positive in myoepithelium around acini but was negative or weak around degenerative acini. Endothelial cells of blood vessels stained strongly with v WF. Cytokeratin KL1 and K8.12 were positive in duct cells of the unaffected area while in the degenerative region they were negative or weak. K8.12 was positive in epimyoepithelial islands, indicating that the epimyoepithelial cells in lymphoepithelial lesions may originate from duct basal cells.

Adult↗

Pressor effect of recombinant human erythropoietin: results of home blood pressure measurements in hemodialysis patients.

We investigated whether the treatment of anemic hemodialysis patients with a low dose of recombinant human erythropoietin (rHEpo) for a short period would increase the blood pressure (BP). Home BP measurements were used to detect minute increases in BP. Fifty-one anemic patients on maintenance hemodialysis with a hematocrit of 25% or less received rHEpo at the dose of 4500 IU/week by the intravenous route for 8 weeks. Overall, rHEpo did not increase the BP whether measured at home or in the clinic (causal BP). Hemoglobin concentration increased significantly from 7.1 +/- 0.7 to 8.8 +/- 0.7 g/dl. Patients were classified into two groups according to the change in mean (M) home BP induced by rHEpo: a pressor group (delta MBP > or = 5 mmHg, n = 17) and a non-pressor group (delta MBP < 5 mmHg, n = 34). The hemoglobin concentration rose significantly in both groups, but there was no change in casual BP. Home blood pressure measurements showed a gradual and continuous rise in BP in the pressor group, but not in the non-pressor group. Patients administered antihypertensive medications before rHEpo treatment accounted for 88% of the former and 50% of the latter groups. Two patients with malignant nephrosclerosis were included in the pressor group. The findings indicate that rHEpo, even given at a low dose for a short period, elevates the BP, as determined by home BP measurement, but not by casual measurements obtained in the clinic.

Adult↗

Transfilter bone induction by Chinese hamster ovary (CHO) cells transfected by DNA encoding bone morphogenetic protein-4.

This study was undertaken to identify the factor responsible for classical transfilter bone induction by a murine osteosarcoma. Chinese hamster ovary (CHO) cells were transfected with the complementary DNA (cDNA) for bone morphogenetic protein-4 (BMP-4) that was purified from a murine (Dunn) osteosarcoma. Diffusion chambers were filled with the cells expressing the gene for BMP-4 and implanted subcutaneously into the flanks of ICR strain nude mice. Ectopic transfilter bone formation was seen consistently on the outer surfaces of the cellulose acetate membranes of chambers containing transfected cells at three weeks after implantation. Bone was not observed on chambers loaded with nontransfected CHO cells. The transfected CHO cells were inoculated into nude mice to form tumors, which were then homogenized, defatted, and bioassayed also in the ICR, nu/nu mice. The cell-free implants consistently elicited new bone and marrow within three weeks, whereas the control implants consisting of nontransfected tumor were not osteoinductive. These experimental results suggest that BMP-4 is one of the molecules responsible for the transfilter bone induction by vital Dunn osteosarcoma cells reported by Heiple and for the ectopic bone induction after implantation of devitalized, freeze-dried Dunn osteosarcoma tissue described originally by Amitani.

Animals↗

[Clinical evaluation of myocardial perfusion imaging with 99mTc-tetrofosmin].

Myocardial perfusion imaging with Tc-99 m-1,2-bis (bis (2-ethoxyethyl) phosphino) ethane (Tc-99 m-tetrofosmin) was performed in 26 patients with ischemic heart disease (IHD) or suspected to have IHD. The agent was administered both at rest and at peak exercise. Exercise and rest studies were performed on the same day or on different days. The injected dose ranged from 296 MBq-740 MBq. Image quality was adequate for diagnosis, and was superior to that of T1-201 scintigraphy. Results from the tetrofosmin imaging corresponded well with findings of T1 scintigraphy, with a segmental concordance of 87%. Sensitivity and specificity were 70% and 93%, respectively. Our results suggested that tetrofosmin could be a promising Tc-99m labeling agent for the evaluation of myocardial perfusion.

Evaluation Studies as Topic↗

Age-specific characteristics of nocturnal blood pressure in a general population in a community of northern Japan.

The age- and gender-specific profile of circadian blood pressure variation was examined by monitoring ambulatory blood pressure (ABP) in 477 untreated subjects in a rural community of northern Japan. Autoregressive spectral analysis demonstrated three major peaks at around 24, 12, and 8 h. We fitted a truncated Fourier series with three harmonics to the blood pressure (BP) data using least squares regression. More than half of the BP and pulse rate periodic curves were bimodal, one-third were trimodal, and the remainder were unimodal. The nadir of BP appeared between 00:00 and 01:30, and that of pulse rate occurred between 00:30 and 02:00. The nadir of systolic and diastolic BP, as well as pulse rate, appeared earlier with increasing age, and the difference between subjects in their 20s and those in their 70s was about 1 h. The amplitude of 24 h BP decreased with increasing age in men, but not in women. This type of information on the circadian BP profile of a general population is useful for the diagnosis and treatment of hypertension.

Adult↗

Characteristics of a community-based distribution of home blood pressure in Ohasama in northern Japan.

OBJECTIVE: To evaluate the distribution, reference values and day-to-day variation of blood pressure of untreated subjects measured at home. DESIGN: Cross-sectional study of a cohort. SETTING: General community in northern Japan. SUBJECTS: Blood pressure was measured in 871 subjects (mean +/- SD age 46.0 +/- 19.5 years, range 7-98, constituting 38.7% of the local population of Uchikawama region, Ohasama) who were not receiving antihypertensive medication. METHODS: Subjects measured their own blood pressure at home at least three times (mean +/- SD 19.7 +/- 8.4) each morning using a semi-automatic oscillometric blood pressure measuring device. Screening blood pressure was measured once. MAIN OUTCOME MEASURES: Distribution of home blood pressure in the study population as a whole and with respect to age and sex, and the distribution of day-to-day variation of home blood pressure were determined. RESULTS: Mean home blood pressure was 117.3 +/- 13.4/69.3 +/- 9.7 mmHg (95% confidence interval 116.4-118.2/68.7-70.0). The 95th centile value was 143/85 mmHg, mean+SD 131/79 mmHg and mean + 2SD 144/89 mmHg. Mean screening blood pressure was 126.2 +/- 18.9/72.1 +/- 11.7 mmHg (95th centile 159/92 mmHg). Age- and sex-specific 95th centile values as well as mean +/- SD were obtained. Mean+SD, mean + 2SD and the 95th centile values obtained as reference upper limits of home blood pressure from subjects identified as normotensive by screening blood pressure (n = 707) were 125/77, 137/86 and 134/83 mmHg, respectively. Home blood pressure increased gradually with increasing age in both men and women, although blood pressure was significantly higher in men until 50 years of age. Day-to-day variation of home systolic blood pressure also increased with age. CONCLUSION: Since the distribution of home blood pressure values was affected by age and sex, age- and sex-matched reference values for home blood pressure should be established. Home blood pressure values in elderly subjects should be evaluated carefully, since these exhibit greater day-to-day variation.

Adolescent↗

Ambulatory blood pressure of adults in Ohasama, Japan.

We performed a cross-sectional study in a small town in northern Japan to evaluate the distribution, reference values, and daily variation in ambulatory blood pressure. A total of 705 subjects (229 men aged 61.3 +/- 13.4 years [mean +/- SD] and 476 women aged 57.5 +/- 13.3 years; 41.1% of the regional adult population, n = 1716), including those treated with antihypertensive drugs (n = 231, 66.5 +/- 9.5 years) as well as untreated subjects (n = 474, 55.0 +/- 13.5 years), participated in the study. Both ambulatory and screening blood pressures were measured in 659 subjects. Ambulatory blood pressure was measured with an automatic device (Colin ABPM-630). The 24-hour ambulatory blood pressure in the total population was 121.7 +/- 13.0/71.1 +/- 7.6 mm Hg (95th percentile value [95%] = 146/85 mm Hg). The corresponding value in the untreated subjects was 119.4 +/- 12.5/70.1 +/- 7.4 mm Hg (95% = 144/83 mm Hg). The 24-hour average ambulatory blood pressure was 118.0 +/- 11.1/69.4 +/- 6.8 mm Hg (95% = 139/81 mm Hg) in subjects identified as normotensive by their screening blood pressure (n = 448, 57.2 +/- 13.1 years) and 133.6 +/- 14.2/78.9 +/- 8.8 mm Hg in those identified as hypertensive by their screening blood pressure (n = 73, 63.1 +/- 10.6 years). Based on the mean+SD of the 24-hour ambulatory blood pressure in the normotensive subjects by their screening blood pressure (129/76 mm Hg), the 24-hour ambulatory blood pressures in 25 (34.2%) of these 73 hypertensive subjects by screening blood pressure were below this level. Nine (2%) of 448 normotensive subjects by screening blood pressure were above the mean+2 SDs (140/83 mm Hg) of the 24-hour ambulatory blood pressure in the normotensive group by screening blood pressure. Ambulatory and screening blood pressures increased with age. The age-dependent increase in ambulatory blood pressure was less apparent in men. The 24-hour average pulse rate decreased with age. The daily variation in ambulatory blood pressure (standard deviation) increased with age, whereas that of pulse rate decreased with age. Increases in blood pressure variation were observed in nighttime and daytime blood pressure values. The differences between day versus night ambulatory blood pressures decreased with age in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Rest and stress myocardial perfusion imaging on the same day with two injections of 99mTc-tetrofosmin].

99mTc-tetrofosmin myocardial perfusion imagings under different protocols were performed at rest and stress on the same day. In the stress/rest protocol, the exercise study was carried out first, and then the rest one followed. Eight patients were involved in the stress/rest protocol. Seven patients were examined in the reverse, rest/stress protocol. In any protocols, the injection interval was 3 hours, and injection doses in the first and second studies were 370 MBq and 740 MBq, respectively. Myocardial counts were obtained by placing region of interest over the myocardial walls in short axial SPECT images. Based on myocardial counts from the first injection and the wash-out rate of tetrofosmin, we calculated, at the second imaging, counts caused from the first injection. Approximately 20-25% of counts in the second study were found to be caused from the residual radiotracer. The residual radiotracers affected the interpretation of imagings of two patients we examined: one with marked reversible ischemia examined in the stress/rest protocol and the other with mild ischemic change examined in the rest/stress one. Our results suggested that some modifications of studies, such as the increase in the injection intervals or the reduce of the first-to-second dose ratio, might be necessary to conduct the same day protocols.

Exercise Test↗

Polylactic acid-polyethylene glycol block copolymer. A new biodegradable synthetic carrier for bone morphogenetic protein.

A new biodegradable polymer, a polylactic acid-polyethylene glycol (PLA-PEG) block copolymer, proved to be an effective and suitable carrier for bone morphogenetic protein (BMP). Composites of semipurified BMP and PLA-PEG consisting of a PLA segment with a molecular weight (MW) of 650 d and a PEG segment with a MW of 200 d (PLA-PEG 650-200) were implanted under the fasciae of the dorsal muscles of mice. Three weeks after implantation, the PLA-PEG 650-200/BMP composites were completely absorbed and replaced by newly induced bone with hematopoietic marrow. The composites induced twice as much bone as composites of BMP and a 650-d PLA homopolymer. Results indicate that of all the biodegradable synthetic polymers the authors have tested, PLA-PEG 650-200 is the most suitable and effective BMP carrier. Composites of PLA-PEG 650-200/BMP and hydroxyapatite powder (HAP) also induced ectopic bone formation. Because PLA-PEG 650-200/BMP is viscous and semiliquid and PLA-PEG 650-200/BMP/HAP is doughy and plastic, the former can be used as an injectable osteoinductive material and the latter as a plastic mold.

Animals↗

Purification and characterization of a bone-inducing protein from a murine osteosarcoma (Dunn type).

A protein fraction capable of eliciting cartilage or bone formation in vivo was purified more than 100,000-fold from a murine osteosarcoma (Dunn type). Intramuscular implantation of as little as 20 ng of the purified protein with 2 mg of pure skin collagen consistently induced ectopic new bone formation. The apparent molecular size of the purified protein was 32 kd on sodium dodecylsulfate-polyacrylamide gel electrophoresis. On reduction, the 32-kd protein split into subunits with the same partial amino acid sequences, and these partial sequences were identical to those of human bone morphogenetic protein-2B (BMP-4) which is assumed to be a member of the transforming growth factor-beta superfamily.

Amino Acid Sequence↗

Analysis of carrot genes for proliferating cell nuclear antigen homologs with the aid of the polymerase chain reaction.

We designed a polymerase chain reaction-based strategy to obtain information about the origin and distribution of a newly discovered proliferating cell nuclear antigen (PCNA) homolog. Carrot genomic segments were amplified using degenerate primers for two conserved regions of known PCNA homologs. The genes encoding the larger PCNA as well as typical PCNA contained introns. Thus, unlike processed PCNA pseudogenes in mammals, the larger homolog is not generated through reverse transcription of a typical PCNA mRNA. Moreover, introns of the larger PCNA homolog were positioned at the characteristic sites in plant PCNA genes. Attempts to amplify cDNA for an additional PCNA homolog from mammalian cells have been unsuccessful. These results suggest that the larger PCNA homolog was generated, presumably through gene duplication, after the divergence of the Planta and Animalia.

Amino Acid Sequence↗

Identification of carrot cDNA clones encoding a second putative proliferating cell-nuclear antigen, DNA polymerase delta auxiliary protein.

The proliferating cell-nuclear antigen (PCNA) plays a key role in the control of eukaryotic DNA replication. We have isolated two cross-hybridizing groups of cDNA encoding carrot homologs of PCNA. Sequence analysis and Southern-blot experiments showed that the cDNA were derived from two distinct genes. One corresponded to the typical PCNA, which is known to be highly conserved in eukaryotes from yeast to man; its mRNA is 1.2 kb in size and the calculated molecular mass of the protein is 29 kDa. The other encoded a larger PCNA homolog which has not previously been reported; the mRNA is 1.5 kb in size, the N-terminal three quarters (calculated molecular mass, 29 kDa) of the protein product is 88% identical at the amino acid level to the typical PCNA, but the protein has an extra C-terminal domain of 11 kDa. Both PCNA homologs were apparently coexpressed concomitant with somatic embryogenesis. The mRNA level of the novel homolog is 10-20% that of the typical PCNA in the embryos. The presence of the second putative PCNA may provide new insight into studies on the mechanism of DNA replication in eukaryotes.

Amino Acid Sequence↗