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Biomedical subjects

J Hashimoto

Publications and source records attributed to J Hashimoto.

At least 73 records · Page 4Linked to original sources

Cell-cycle-regulated transcription of A- and B-type plant cyclin genes in synchronous cultures.

Synchronously dividing cell cultures of Catharanthus roseus were used to isolate cDNAs for two mitotic cyclins, named CYS and CYM. The deduced protein sequence of CYS is similar to that of A-type cyclins, and CYM belongs to the group of B-type cyclins. In a fashion similar to the pattern of expression seen for A-type and B-type cyclins in mammalian cells, CYS is expressed before CYM in C. roseus cells during the cell cycle. CYS mRNA accumulated at the onset of S phase and disappeared early in the G2 phase, whereas CYM mRNA was detected in the G2 and M phases of the cell cycle. Tobacco homologs of the two genes showed similar cell-cycle dependent expression patterns in synchronous cultures of tobacco BY2 cells. In both systems, CYS was expressed much earlier in the cell cycle than most other plant A-type cyclins, and hence CYS along with the soybean cyc1GM can be classified into a distinct subclass. The activities of CYM and CYS promoters during the cell cycle were analyzed in stably transformed tobacco BY2 cells. Cyclin promoter sequences of 0.5 kb could confer the typical cell-cycle-dependent expression to the beta-glucuronidase (GUS) reporter gene: the CYS promoter directed S-phase-specific expression, whereas the CYM promoter drove M-phase-specific expression. These results indicate the important role of transcriptional regulation in the oscillations of cyclin mRNA levels during the cell cycle.

Cell Cycle↗

Scatter and attenuation correction in technetium-99m brain SPECT.

UNLABELLED: We propose a practical method for scatter and attenuation compensation in 99mTc-ECD brain SPECT using a simultaneous emission CT (ECT) and transmission CT (TCT) acquisition system that includes the following major components: (a) triple-headed SPECT gamma camera equipped with fanbeam collimators; (b) external line sources containing 99mTc placed at the focal lines of the collimators; and (c) scatter correction by the triple-energy-window (TEW) method. METHODS: Projection images were obtained over a 360 degrees rotation scan. After acquisition, scatter correction was performed using the TEW method, which corrected scattered photons pixel by pixel in the projection data. Scatter-corrected ECT images were compensated for attenuation using the TCT images with Chang's iterative method, and were converted to activity concentration (kBq/ml) images by obtaining a cross-calibration scan. After validating this method with phantom studies, it was applied to clinical brain imaging using a combination of 925 MBq 99mTc-ECD as a radiopharmaceutical and 222 MBq 99mTc as an external source. ECT and TCT data were acquired separately or simultaneously. RESULTS: SPECT quantification and image quality were improved by performing this correction. The activity concentration images obtained with the simultaneous acquisition were almost identical to those obtained with the separate acquisition. CONCLUSION: This method was clinically practical and cost-effective for reconstructing quantitative 99mTc brain SPECT images.

Brain↗

Osteoclastogenesis in iliac bone marrow of patients with rheumatoid arthritis.

OBJECTIVE: To investigate osteoclastogenesis in bone marrow cells from patients with various pathogenic backgrounds known to induce osteoporosis, to identify specific factors that may cause generalized osteoporosis in patients with rheumatoid arthritis (RA). METHODS: Bone marrow blood was obtained from 59 women, 36 with RA and 23 without RA. Patients with RA were classified as severe (26) and mild RA (10: 5 patients with and 5 without corticosteroid therapy). The non-RA subjects were divided into 3 groups, premenopausal (7), menopausal (8), and elderly (8). As a marker of bone resorption, the pyridinoline crosslinked telopeptide domain of type I collagen (ICTP) concentration in the bone marrow supernatant was measured by radioimmunoassay. The bone marrow cells were cultured 14 days in the presence or absence of autologous bone marrow supernatant; then the number of tartrate resistant acid phosphatase positive multinucleated cells (TRAP positive MNC) was counted as an indicator of osteoclastogenesis. RESULTS: ICTP concentration of the bone marrow supernatant and the number of TRAP positive MNC showed remarkable enhancement in some patients with severe RA, but these features were not observed in the 3 control groups. CONCLUSION: Increased bone resorption and enhanced osteoclastogenesis were specifically observed in the iliac bone marrow of patients with RA, especially those with severe RA. These phenomena can be considered to accompany generalized osteoporosis in RA.

Adult↗

[Typical normal cases and normal cases with abnormal image pattern in every myocardial SPECT radiopharmaceutical].

Working group of cardiac nuclear medicine was made as a Japanese part of society of international cardiac nuclear medicine under the cooperation between Japanese society of nuclear medicine and Japanese society of cardiology. We investigated typical normal cases and normal cases with abnormal image pattern in every myocardial SPECT radiopharmaceutical as one of the research activity of working group. From 11 faculties, 16 T1 cases, 14 BMIPP cases, 8 MIBG cases, 8 MIBI cases and 14 tetrofosmin cases were submitted as typical normal cases, and 12 T1 cases, 5 BMIPP cases, 12 MIBG cases, 10 MIBI cases and 5 tetrofosmin cases were submitted as normal cases with abnormal image pattern. We summarized the condition of SPECT data acquisition of each faculties. And we added the discussion from literature about how to discriminate normal cases with abnormal image pattern from abnormal cases. In MIBG, patterns of typical normal cases and normal cases with abnormal image pattern were slightly different from other 4 pharmaceuticals. In other 4 pharmaceuticals, diaphragmatic attenuation, breast attenuation, apical thinning and others were presented as normal cases with abnormal image pattern.

3-Iodobenzylguanidine↗

[Can 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) evaluate the renal function without blood sampling?: consensus report from multicenter study].

A multicenter study was undertaken in Japan to evaluate the correlation between the percentage of renal uptake of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) estimated by the count-based gamma camera method and the blood clearance of 99mTc-MAG3. Twenty four centers were enrolled and 172 cases were finally analyzed in this study. The renal clearance of 99mTc-MAG3 (TER) was obtained by using a single blood sample taken at 44 min after injection. Comparison of TER and renal uptake provided a coefficient of correlation of 0.874; suggesting that sufficiently accurate quantification of renal function could be obtained from the renal uptake estimate by the gamma camera method. This study also showed that the comparison of renal function might be feasible among patients under the same protocols, although precise and careful consideration is required in each center.

Adolescent↗

A cDNA cloning of human AEBP1 from primary cultured osteoblasts and its expression in a differentiating osteoblastic cell line.

By comparing lists of 3'-directed partial cDNA sequences (gene signatures) randomly collected from various tissues, genes uniquely expressed in individual tissue can be identified. A full length cDNA clone, corresponding to one such gene signature, unique to human osteoblast and adipose tissue, was isolated. This cDNA clone encodes a 845-amino acid protein that is almost identical to the mouse adipocyte transcription factor AEBP1 except that it has additional 105 amino acids in the N terminus. A northern hybridization showed that in the differentiating murine osteoblastic cell line, AEBP1 is also expressed but that it is shut off in the final calcification phase, suggesting a transcriptional repressive effect on genes for bone formation.

3T3 Cells↗

Circadian blood pressure variation related to morbidity and mortality from cerebrovascular and cardiovascular diseases.

The mortality rate of stroke has decreased dramatically over the past 30 years in Japan, but the prevalence of cerebral infarction has increased, mainly because of the higher incidence of nonfatal cerebral infarction in the elderly. Significant advances in the development of antihypertensive drugs over the last 30 years have contributed to the decrease in stroke mortality, but antihypertensive treatment appears to relate to an increase in the prevalence of cerebral infarction in the elderly. We investigated the risks of low BP levels determined by ambulatory BP monitoring and home BP measurements to clarify the previously reported J-shaped relationships between the incidence of ischemic cardiovascular disease and BP levels after treatment. A long-term prospective study of all causes of mortality and cerebrovascular and cardiovascular mortality has been conducted in Ohasama, Japan, since 1987. Cox proportional hazard model after adjusting for age and sex demonstrated that during a 5-year follow-up period involving 893 of the subjects aged 50 years and over in this cohort, those with the lowest quintile of ambulatory BP levels exhibited a significantly high hazard ratio of cardiovascular as well as all causes of mortality. During the same follow-up period in 1,226 subjects aged 50 years and over, those with the lowest and highest quintiles of home BP levels demonstrated a significantly high hazard ratio of cardiovascular as well as all causes of mortality (i.e., J-shaped relationship). The amplitude of the fall in nocturnal BP obtained by ambulatory BP monitoring correlated positively with the severity of silent cerebrovascular lesions in elderly women, but not in elderly men. These results suggest the significantly high risk associated with low BP levels, which can be determined only by ambulatory and home BP measurements, but not by casual BP measurements.

Age Factors↗

Plant cyclins: a unified nomenclature for plant A-, B- and D-type cyclins based on sequence organization.

The comparative analysis of a large number of plant cyclins of the A/B family has recently revealed that plants possess two distinct B-type groups and three distinct A-type groups of cyclins. Despite earlier uncertainties, this large-scale comparative analysis has allowed an unequivocal definition of plant cyclins into either A or B classes. We present here the most important results obtained in this study, and extend them to the case of plant D-type cyclins, in which three groups are identified. For each of the plant cyclin groups, consensus sequences have been established and a new, rational, plant-wide naming system is proposed in accordance with the guidelines of the Commission on Plant Gene Nomenclature. This nomenclature is based on the animal system indicating cyclin classes by an upper-case roman letter, and distinct groups within these classes by an arabic numeral suffix. The naming of plant cyclin classes is chosen to indicate homology to their closest animal class. The revised nomenclature of all described plant cyclins is presented, with their classification into groups CycA1, CycA2, CycA3, CycB1, CycB2, CycD1, CycD2 and CycD3.

Amino Acid Sequence↗

Evaluation of SPET quantification of simultaneous emission and transmission imaging of the brain using a multidetector SPET system with the TEW scatter compensation method and fan-beam collimation.

A gamma camera system which is able to acquire simultaneous single-photon emission tomographic (SPET) data and gamma ray transmission computed tomography (TCT) data for brain study using external rod sources and fan-beam collimators was developed and evaluated. Since the three external rod sources were located at the focal points of fan-beam collimators, which also happened to be the apexes of the equilateral triangle defined by the three detectors, simultaneous SPET and TCT scan could be performed using a 120 degrees shared scan. Therefore, the proposed system required less than one-third of the scanning time of a single-head system. Since the combination of rod sources and fan-beam collimators decreased the scatter component in transmission data without a slit collimator for each rod source, the radioactivity of the rod source was less than one-tenth of the previous investigations. For evaluation, we used two isotopes, thallium-201 for TCT and technetium-99m for SPET. The cross-contamination of transmission and emission was well compensated using the triple energy window (TEW) method. In a separate TCT scan, the measured attenuation coefficient of 201Tl for water was 0.19+/-0.01 cm-1, while in a simultaneous scan, it was 0. 20+/-0.01 cm-1. The measured attenuation coefficient for water agreed well with the narrow-beam (theoretical) value of 0.187 cm-1. In SPET images, scatter compensation was also performed using the TEW method and attenuation compensation was done using the measured attenuation map. The results showed the feasibility of simultaneous SPET and TCT scanning using the TEW method to obtain quantitative SPET images.

Brain↗

Augmentation of antitumor effect by combined administration with interleukin-2 and sizofiran, a single glucan, on murine EL-4 lymphoma.

The antitumor effect of the combined administration with recombinant human interleukin-2 (rIL-2) and sizofiran (SPG), a single glucan of Shizophyllum commune Fries, was studied in vivo in C57BL/6 mice intraperitoneally inoculated with EL-4 lymphoma. The effect was evaluated by a) comparing the survival time of the mice, b) analysis of the intraperitoneal cell population in Giemsa-stained specimens, c) surface marker analysis of peritoneal exudative cells with flow cytometry, d) cytotoxic assay of cells against EL-4 and Yac-1 lymphoma, and e) elimination of some cell populations by monoclonal antibodies, to identify the antitumor-effector cells showing cytotoxic activity. The survival of mice given both rIL-2 and SPG was significantly longer than the control mice or those given SPG alone or rIL-2 alone. 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 might be effective in reducing lymphoma cells. The combination of rIL-2 and SPG administration appears to activate the antitumor-immune response at the tumor site more effectively than when either agent was administered alone.

Animals↗

Effect of sizofiran on regional lymph nodes in patients with head and neck cancer.

The immunomodulating effects of preoperative sizofiran (SPG) administration on regional lymph nodes were studied in patients with stage III or IV head and neck cancer, by comparing the immunofunction of peripheral blood. The regional lymph nodes were dissected surgically, and freshly obtained mononuclear cells were studied to investigate the interleukin 2 (IL-2) production, the LAK and NK activities, and the quantitative analysis of the surface phenotype of the mononuclear cells. The results indicated that SPG enhanced immunological activities in the regional lymph nodes, as shown by increased IL-2 production and cytotoxic activities of the effector cells (NK, LAK), and increased helper T lymphocytes (CD4+) in the tumor-uninvolved lymph nodes. The immunofunction following SPG administration was attenuated, but was still augmented in the regional lymph nodes with metastases. Therefore, SPG was found to be a biologic response modifier to enhance the immunofunctions of the regional lymph node in patients with head and neck cancer.

Adjuvants, Immunologic↗

Inhibitory effect of metastasis by combined administration with interleukin-2 and sizofiran, a single glucan--immunohistochemical study.

Innovations in methods of combined administration with other BRM or chemotherapeutic drugs have been discussed. We have reported that combined administration with recombinant interleukin-2 (rIL-2) and sizofiran (SPG) is effective in prolonging survival time of C57BL/6 mice intraperitoneally inoculated with EL-4 lymphoma. The immunomechanisms of the combined administration were clarified investigating the intraperitoneal cell population in the primary tumor site, especially the tumor infiltrating lymphocyte (TIL) quantitatively. In the present study, to clarify the antitumor effects of combined administration with rIL-2 and SPG on the metastatic sites, the immunomechanisms of the suppressive effects of combined administration on the metastasis were studied in EL-4 lymphoma cells intraperitoneally transplanted to mice. Inasmuch as EL-4 lymphoma shows rapid hepatosplenic metastasis, we studied the metastatic foci in the liver and the spleen semiquantitatively in investigating the histopathological and immunohistochemical findings of the metastatic foci, especially the TIL. The metastatic foci were stained by hematoxylin-eosin (HE) and monoclonal antibodies (L3T4, Lyt2, asialo GM1, Mac-1, and Ia). The combined administration resulted in: 1) fewer infiltrating tumor cells, 2) more lymphocytic infiltration, and 3) more antitumor effector cells (cytotoxic T cells: Lyt2 and natural killer cells: asialo GM1), macrophages (Mac-1), helper T cells (L3T4), and cells with MHC-class-II antigen (Ia) than did administration of rIL-2 alone or SPG alone, or no administration of these two at all. Combined administration with rIL-2 and SPG appears to activate antitumor-immune response at the metastatic site more effectively than when either agent is administered alone.

Animals↗

Comparison of cationic myocardial perfusion agents: characteristics of accumulation in cultured smooth muscle cells.

The uptake and washout kinetics of two cationic lipophilic 99mTc-labeled myocardial perfusion agents, 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) 99mTc-1,2-bis[bis-2-ethoxyethyl)-phosphino]ethane (99mTc-Tetrofosmin), were studied in cultured smooth muscle cells and compared to the conventional myocardial perfusion agent, 201Tl. Both 99mTc-MIBI and 99mTc-Tetrofosmin had a 4-fold greater uptake then 201Tl, and they were washed out of cells through similar kinetics which had slower rates than 201Tl. Incubation with metabolism inhibitors had a modest influence on the uptake of these two 99mTc-labeled agents, although their extent and inhibited sites were slightly different. Ion transport inhibitors did not affect the uptake of 99mTc-MIBI, although the 99mTc-Tetrofosmin uptake was slightly inhibited when the Ca2+ channel was blocked. Our studies indicate that 99mTc-MIBI and 99mTc-Tetrofosmin were taken up by smooth muscle cells in similar pharmacokinetic patterns, but their accumulation reflected a different meaning for cell viability.

Antimetabolites↗

Role of vasopressin in neurocardiogenic responses to hemorrhage in conscious rats.

Vasovagal reflexes, such as hypotension and bradycardia, are induced by rapid hemorrhage and mimic neurocardiogenic reflexes in mammals. We examined the role of vasopressin in the neurocardiogenic responses to mild, rapid hemorrhage (1 mL/100 g for 30 seconds) and severe hemorrhage (1 mL/100 g body wt for 30 seconds repeated three times at 11-minute intervals) in homozygous Brattleboro and Long-Evans rats. Mild, rapid hemorrhage induced severe bradycardia and hypotension only in Long-Evans rats. Exogenous vasopressin (1.85 pmol/kg per minute for 1 hour) restored both the bradycardic and hypotensive responses in Brattleboro rats. DDAVP, a vasopressin V2-receptor agonist (0.19 pmol/kg per minute for 24 hours), did not affect the cardiovascular responses to hemorrhage in Brattleboro rats, although it maintained urine production within normal limits. However, OPC-31260 (21.6 mumol/kg IV), a vasopressin V2-receptor antagonist, attenuated both the hypotensive and bradycardic responses to hemorrhage in Long-Evans rats. A vasopressin V1-receptor antagonist attenuated bradycardia and delayed the recovery of arterial pressure after hemorrhage but did not affect the hypotension that occurred immediately after hemorrhage in Long-Evans rats. Methylatropine also attenuated both the bradycardic and hypotensive responses induced by hemorrhage, but propranolol had no effect on the cardiovascular responses to hemorrhage in Long-Evans rats. The recovery of arterial pressure after repeated hemorrhage was less adequate in Brattleboro rats than in Long-Evans rats. Our results suggest that the neurocardiogenic responses to hemorrhage, especially hypotension, may be related to vasodilation induced by a V2-receptor-mediated mechanism and by the vagal reflex, both of which are substantiated by the existence of vasopressin. The coexistence of V1- and V2-receptor mechanisms may be necessary for the hypotensive response to hemorrhage. We found that a V2-receptor antagonist attenuated the hypotension mediated by the so-called neurocardiogenic reflex.

Acute Disease↗

Transient accumulation of proteins at interrod and rod enamel growth sites.

Conceptually, there should be a brief interval in time when newly secreted proteins "pile up" at secretory sites just outside the membrane of ameloblasts. Indeed, previous cytochemical studies have suggested that glycosylated and/or sulfated glycoproteins accumulate at enamel growth sites. Colloidal gold lectin cytochemistry and immunocytochemistry with antibodies to enamel proteins and phosphoserine, combined with cycloheximide and brefeldin A to inhibit protein synthesis and secretion, were applied to characterize the distribution of newly formed proteins at enamel interrod and rod growth sites. Although enamel growth sites show a "rarefied" appearance, the results indicate that one or more subclasses of enamel proteins accumulate near the cell surface at sites where elongation of enamel crystallites contributes to thickening of the enamel layer. These proteins are glycosylated and/or phosphorylated and, at least in the case of the glycosylated ones, are rapidly processed after they are released extracellularly. In contrast, immunolabeling for amelogenins is generally weaker near the cell surface and more intense at a short distance away from the site where crystallites elongate. The data suggest that the enamel proteins accumulating at growth sites likely belong to the non-amelogenin category and play a transient role in promoting the lengthening of crystallites. It is concluded that areas near the ameloblast membrane where certain enamel proteins accumulate in fact constitute the equivalent of a mineralization front.

Ameloblasts↗

Analysis of circadian variation of blood pressure and heart rate in dexamethasone-induced hypertensive rats.

We studied the effect of the chronic oral administration of dexamethasone (dexa) on arterial blood pressure (BP) in conscious rats. Special attention was paid to the effects of dexa on circadian rhythm of BP. As determined by the tail cuff-method, BP in the dexa-treated group was significantly higher than in the control group 24 h after treatment, then increased gradually, reaching a plateau on the 7th day of treatment. At that time, the difference in BP between the two groups was approximately 30 mmHg. When monitored directly and continuously on day 10, mean arterial pressure (MAP) in the dexa-treated group exceeded that of the control group by approximately 15 mmHg throughout the monitoring period. Thus, the circadian rhythm of MAP was sustained in the dexa-treated group, which was in contrast to the previously reported elimination of circadian rhythm in humans. In addition, the increase in BP may have been overestimated by tail-cuff plethysmography, possibly owing to a hightended cardiovascular reactivity to environmental stimuli in dexa-treated animals.

Administration, Oral↗

[Scatter and attenuation correction for quantitative myocardial SPECT imaging].

We performed scatter and attenuation compensation in 201Tl myocardial SPECT using the triple-energy-window (TEW) scatter correction method and 99mTc transmission scan (TCT). A dual-headed SPECT gammacamera system equipped with parallel-hole collimators was employed for imaging and a sheet source for TCT was attached to the surface of one of the two detectors. Two imaging protocols, a sequential mode and a simultaneous mode, were examined. In the sequential mode, TCT was performed prior to the administration of the tracer and then ECT was carried out. On the other hand, the injection was followed by a simultaneous transmission-emission scan, in the simultaneous mode. Results of phantom studies showed that reconstructed SPECT values of the whole myocardium were almost equal to the true value with errors of less than 5 per cent, and that more homogeneous images were obtained by performing scatter and attenuation correction. We conclude that this correction method was clinically practical and cost-effective because it uses parallel-hole collimators and does not require fan-beam collimators which may produce truncation artifacts.

Heart↗

[A case of multiple pulmonary leiomyomatous hamartoma].

A 45-year-old woman with multiple pulmonary leiomyomatous hamartoma was reported. Multiple round shadows were observed in the chest X-ray film of mass examination. Retrospectively chest X-ray films revealed an increase in size and number of pulmonary nodules in three years. Metastatic pulmonary tumors were suspected. Primary site was unclear. Calcified myoma uteri was recognized. The pathological diagnosis under diagnostic thoracotomy was multiple leiomyomatous hamartoma. After ten months of medical castration using superactive analogue of LHRH (buserelin) by intranasal spray, chest X-ray film showed a slight decrease in size of nodular shadows in the right middle lung field.

Female↗