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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 757 records · Page 42Linked to original sources

In vitro purging of clonogenic leukemic cells from human bone marrow by heat: simulation experiments for autologous bone marrow transplantation.

In order to apply a simple purging method by heat to autologous bone marrow transplantation (ABMT), we have revaluated the ability to purge clonogenic leukemic cells from the simulated marrow mixture of normal marrow cells and leukemic cell lines (HL-60, Molt-3 and HEL) in vitro by heat, using two different clonogenic assays for normal granulocyte-macrophage progenitors (CFU-GM) and leukemic cell lines. It appeared that in vitro hyperthermia (42 degrees C for 120 min) is able to selectively remove clonogenic leukemic cells from simulated tumor cell-normal marrow mixtures even when leukemic cell concentrations are increased up to 3 x 10(6) cells/ml in vitro, and results in a 4-6 log destruction of clonogenic leukemic cells/ml according to a limiting dilution assay, while leaving half of normal CFU-GM surviving. The hyperthermic purging of clonogenic leukemic cells was not affected in the presence of normal marrow cells in vitro. This high level of clonogenic leukemic cell depletion by heat correlated with that of immunologic and pharmacologic studies. These results suggest that in vitro hyperthermia could be applied effectively and safely for the elimination of residual clonogenic leukemic cells in autologous marrow grafts before ABMT.

Bone Marrow Purging↗

The role of radiotherapy in the treatment of primary mediastinal seminoma.

Nine patients with primary mediastinal seminoma were treated with radiotherapy. All patients achieved complete response on chest radiography. None of the three patients treated with whole mediastinal irradiation relapsed. Four of the six patients with involved-field irradiation had marginal relapses, suggesting the efficacy of the whole mediastinal irradiation.

Adolescent↗

Current status of Image Save and Carry (IS&C) standardization.

Image Save And Carry (IS&C) was planned to be an off-line information system for transmission and exchange of medical images and information between a medical facility's different divisions as well as between other hospitals. The IS&C committee defines file format for magneto-optical disk, the data format and representation, media compatibility and data security and technological assessment. A 'zone management method' which contributes to a rapid access of data in the recording media is used for IS&C file management. The IS&C standard holds as much conformation as possible in order to coordinate with ACR-NEMA (American College of Radiology-National Electrical Manufacturers' Association) and MIPS (Medical Information Processing Systems) standards. The IS&C data format is based upon the ACR-NEMA/MIPS standard. A major difference between the ACR-NEMA/MIPS standard and IS&C standard is that the IS&C standard is expected to serve for recording all kinds of medical information (e.g., diagnostic reports, endoscopic images and electrocardiograms), including X-ray images. Applications to PACS, teaching files, personal electronic health and medical records are promising. The booklet of IS&C standard will be published in the spring of 1992 by the IS&C committee.

Computer Communication Networks↗

Evaluation of the 111In-(Sn)-citrate method to label antibodies for radioimmunotargeting studies.

Monoclonal antibody against carcinoembryonic antigen (CEA) was labeled by the 111In-(Sn)-citrate technique and its characteristics were determined from the point of radioimmunotargeting studies. Antibodies of high specific radioactivity could be labeled with a high labeling yield of greater than 90% without any further purification step, and without loss of immunoreactivity. In biodistribution studies using nude mice bearing CEA-producing tumors, an extremely high tumor-to-blood ratio (40 on day 6) was obtained since 111In in the blood cleared very rapidly, but nonspecific 111In localized in the liver and spleen should be seriously considered.

Animals↗

Mechanism underlying the changes in plasma potassium concentration during infusion of isosmotic nonelectrolyte solution.

Generally, during infusion of an isosmotic nonelectrolyte solution that permeates the cell membrane, plasma K+ concentration ([K+]pl) either does not change or it increases slightly. The mechanism underlying this [K+]pl change has not been clarified. We continuously monitored the [K+]pl and plasma Na+ concentration ([Na+]pl) for 10 min during isosmotic mannitol infusion of 1.6 ml/100 g body weight in rats with intact kidney function (intact mannitol group). In addition, in nephrectomized rats, we compared the [K+]pl change during infusion with isosmotic mannitol (which permeates the cell membrane; mannitol nephrectomized group) with that during infusion with isosmotic sucrose (which does not permeate the cell membrane; sucrose nephrectomized group) to evaluate the effect of cell volume regulation. In the intact mannitol group, [Na+]pl decreased with dilution, and [K+]pl remained relatively constant. In the sucrose nephrectomized group, [K+]pl decreased by the same percentage as [Na+]pl and gradually increased to greater than the control level. In the mannitol nephrectomized group, however, [K+]pl increased immediately after the beginning of the infusion and reached the same level as that in the sucrose nephrectomized group. To confirm that the difference in [K+]pl between the mannitol and sucrose nephrectomized groups was dependent on cell volume regulation, we investigated the changes in mean corpuscular volume of red blood cells, using a Coulter counter. This value remained constant during isosmotic sucrose infusion but increased during isosmotic mannitol infusion, returning to the original volume after the infusion. We kept [HCO3-] and pH constant throughout the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Epithelial-myoepithelial carcinoma of the parotid gland in a child.

A rare case of epithelial-myoepithelial carcinoma of the parotid gland, which occurred in a child, is reported. An 8-year-old boy presented with swelling of the right parotid gland. He underwent total parotidectomy followed by irradiation for a parotid gland tumor. Three years after the operation, a recurrent tumor invading the base of the skull and the brain and metastases in the lung were noted. The patient expired in spite of extirpation of the intracranial recurrent tumor. The resected tumor showed a characteristic histologic feature: double-layered tubular structures composed of inner dark cells (epithelial cells) and outer clear cells (myoepithelial cells). This patient may be the youngest one with the epithelial-myoepithelial carcinoma reported in the literature.

Carcinoma↗

TFIIA induces conformational changes in TFIID via interactions with the basic repeat.

DNA-binding studies with Saccharomyces cerevisiae TFIID point mutants indicated that TFIIA interacts with the basic repeat region of TFIID and induces structural changes. The latter was shown by the ability of TFIIA to compensate for TFIID point mutants defective for DNA binding. Interaction with TFIIA also rendered TFIID binding temperature independent, thus mimicking the effect of removing the nonconserved N terminus of TFIID. In addition, N-terminal truncation of the TFIID point mutants defective for DNA binding mimicked the ability of TFIIA to restore DNA binding of those mutants. Taken together, these results suggest that TFIIA enhances TFIID binding to DNA by eliminating an otherwise inhibitory effect of the nonconserved N terminus of TFIID. Furthermore, analyses of TFIID contact points on DNA and binding studies with TATA-containing oligonucleotide probes showed that TFIIA decreases the effect of sequences flanking the adenovirus major late TATA element on TFIID binding to DNA, suggesting a possible role of TFIIA in allowing TFIID to recognize a wider variety of promoters.

Base Sequence↗

A case of amniotic band syndrome with bilateral epibulbar choristoma.

An autopsy case of amniotic band syndrome with bilateral epibulbar choristoma is described. The left eye reveals a complex choristoma and the right eye a dermis-like choristoma. Both choristomatous lesions included lenticular tissue suggesting that rupture of the amnion, which is the initial event of amniotic band syndrome, might have occurred at about the fourth week of gestation. Since the other systemic manifestations of amniotic band syndrome are considered to be compression deformities of the fetus caused by oligohydramnios or amniotic band, the occurrence of epibulbar choristomas in both eyes in this case suggests that a compression mechanism may play a role in the pathogenesis of epibulbar choristoma.

Adult↗

Elevated mean systemic filling pressure due to intermittent positive-pressure ventilation.

To clarify the effect of intermittent positive-pressure ventilation (IPPV) on systemic circulation, mean systemic filling pressure (Psf) and circulating blood volume were measured together with other hemodynamic parameters of capacitance vessel. Change in circulating blood volume was determined by dilution with 51Cr-labeled erythrocytes. Vascular compliance (Cvas) was measured from the change in Psf caused by a bolus injection of blood. These parameters were measured during both spontaneous respiration and IPPV in male Wistar rats anesthetized with pentobarbital sodium. The shift from spontaneous respiration to IPPV reduced cardiac output (CO) by 20.9%. Psf increased significantly, from 7.1 +/- 1.2 to 8.6 +/- 1.1 mmHg. Central venous pressure (Pcv) also increased significantly. The pressure gradient for venous return decreased by 15.6% (from 6.4 to 5.4 mmHg). The resistance to venous return did not change significantly, but there was a significant increase in total peripheral resistance. Neither Cvas nor circulating blood volume was changed significantly by IPPV. These results indicate that during IPPV the increased Pcv attenuates the pressure gradient for venous return and decreases CO and that the compensatory increase in Psf is caused by a blood shift from unstressed to stressed blood volume.

Animals↗

Effect of probenecid on the pharmacokinetics of DQ-2556, a new 3-quaternary ammonium cephalosporin antibiotic, in humans.

A total of 5 healthy volunteers were enrolled in a crossover study on the dose dependency and the effect of probenecid on pharmacokinetics of DQ-2556. They were administered intravenously 0.5 and 1.0 g of DQ-2556, and 1.0 g of DQ-2556 with oral administration of probenecid. The linearity in pharmacokinetics of DQ-2556 was confirmed up to the dose of 1.0 g. In the case of 1.0 g of DQ-2556 with probenecid treatment, the area under the serum concentration-time curve was larger, and total and renal clearances were less than those in the case of 1.0 g of DQ-2556 alone (by approximately 15% for each parameter, p < 0.01). These results demonstrated that DQ-2556 is secreted in the renal tubule, although it is excreted mainly by the glomerular filtration.

Administration, Oral↗

Evidence for defective transmembrane signaling in B cells from patients with Wiskott-Aldrich syndrome.

B lymphocytes from patients expressing the X chromosome-linked immune deficiency disorder, Wiskott-Aldrich syndrome (WAS), fail to produce antibodies in response to stimulation with polysaccharides and other type-2 T cell-independent antigens. To investigate whether this abnormality reflects a defect in the signal transduction cascade normally triggered by ligation of surface immunoglobulin (sIg) on B cells, we have examined early signaling events induced by anti-Ig antibody stimulation of EBV B lymphoblastoid cell lines from WAS patients and healthy controls. Despite the expression of comparable levels of sIg and sIgM on WAS and control EBV B cells, WAS cells failed to manifest the increased proliferation in response to anti-Ig treatment observed in the control cell lines. WAS and control EBV B cells also differed in the magnitude of the change in cytosolic free calcium ([Ca2+]i) induced by sIg ligation; WAS cells showed either markedly diminished or no changes in [Ca2+]i levels whereas control EBV B cells consistently showed increases in [Ca2+]i. Anti-Ig-induced changes in inositol phosphate release were also markedly reduced in WAS compared with control cells. As protein tyrosine phosphorylation is thought to represent a proximal event in the activation of B cells, inducing increases in [Ca2+]i by virtue of tyrosine phosphorylation of phospholipase C (PLC)-gamma, profiles of protein tyrosine phosphorylation and expression of tyrosine-phosphorylated PLC-gamma 1 were compared between WAS and normal EBV B cells before and after sIg cross-linking. These studies revealed that in addition to defective mobilization of Ca2+, the WAS cells manifested little or no increase in tyrosine phosphorylation of PLC-gamma 1 or other intracellular proteins after sIg ligation. Together these results indicate the association of WAS with a defect in the coupling of sIg to signal transduction pathways considered prerequisite for B cell activation, likely at the level of tyrosine phosphorylation. The abnormalities observed in these early transmembrane signaling events in WAS EBV B cells may play a role not only in the nonresponsiveness of WAS patient B cells to certain T independent antigens, but also in the genesis of some of the other cellular deficits exhibited by these patients.

B-Lymphocytes↗

Novel phenoxyalkylamine derivatives. VII. Synthesis and pharmacological activities of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives.

To find a novel alpha-blocker with high alpha-blocking selectivity against dopamine D2-receptor affinity, we performed structural modification of the alkylene chains and the substituents on two benzene rings of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives. The modification of the alkylene chain between the amino moiety in the center of the molecule and the benzene ring (ring A) was found to be the most significant. 5-[2-[[2-(5-Fluoro-2-methoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide (II-4), which possesses 1-methylethyl as the alkylene chain, exhibited high alpha-blocking selectivity as well as potent alpha-blocking activity.

Adrenergic alpha-Antagonists↗

[Studies on early stage changes of peroxide lipid in isoproterenol-induced myocardial injury].

The amount of peroxide lipid in vivo in the early stage of the experimental model of myocardial infarction in a rat induced by the administration of isoproterenol (Isp) was measured as the value of malonic dialdehyde (MDA). The model of myocardial infarction was made by giving 75 mg/kg of Isp to the rat weighing 270 +/- 10 g. After the administration of Isp, the amounts of lipid in the serum and in the myocardial tissue were measured, and a blood chemistry test (glutamic oxaloacetic dehydrogenase, glutamic pyruvic transaminase, lactate dehydrogenase, free fatty acid, creatine kinase) was simultaneously carried out on the serum. The value of the amount of peroxide lipid in the serum began to elevate 3 h after the administration of Isp and reached a maximum value at 6 h. The value of the amount of peroxide lipid in the tissue began to elevate 30 min after the administration and reached a maximum at 3 h. Each blood chemistry disclosed the elevation 30 min after the administration. As mentioned above, the production of peroxide lipid in vivo on the myocardial disorder in the early stage after the administration of Isp and the biochemical changes showed a significant correlation. From these results it is suggested that the myocardial disorder induced by the administration of Isp has already developed at 30 min after the administration.

Animals↗

In vitro pharmacological profile of the novel alpha 1-adrenoceptor antagonist HSR-175.

The pharmacological profile of HSR-175, a new alpha 1-adrenoceptor antagonist, was studied in vitro and compared with those of other alpha 1-antagonists. HSR-175, prazosin, bunazosin and yohimbine competitively antagonized the contractile responses induced by noradrenaline in the dog mesenteric arteries and the rabbit thoracic aorta. The pA2 values for HSR-175 in the dog mesenteric arteries and the rabbit aorta were 10.38 and 9.63, respectively, which were significantly higher than those for prazosin (8.39 and 8.80), bunazosin (8.44 and 8.75) and yohimbine (7.34 and 6.10). HSR-175 also inhibited the sympathetic adrenergic contraction induced by electrical transmural stimulation in the dog mesenteric arteries, and the inhibitory effect of HSR-175 was more potent than those of prazosin and bunazosin. Although HSR-175 also possessed competitive antagonist properties at pre- and postsynaptic alpha 2-adrenoceptors in the rat vas deferens and the dog saphenous veins, those affinities (pA2 = 6.41 and 7.05) were much lower than those at postsynaptic alpha 1-adrenoceptors. Furthermore, HSR-175 at concentration of 10(-6) M showed no inhibition on the contractile responses to 5-HT, histamine, KCl and angiotensin II in the rabbit thoracic aorta. These results indicate that HSR-175 is a very potent and selective alpha 1-adrenoceptor antagonist.

Adrenergic alpha-Antagonists↗

[Effects of smoking and drinking habits and vitamin A intake on serum concentrations of beta-carotene and retinol].

Serum samples from 341 males aged 10 to 59 years were obtained and stored at -40 degrees C until examined for retinol and beta-carotene concentrations by HPLC, and their relationships to smoking habit, alcohol drinking habit and vitamin A intake were studied. In univariate analysis the serum beta-carotene level was significantly lower in the smokers than in the non-smokers (smokers: 4.6 micrograms/dl, non-smokers: 7.1 micrograms/dl, p less than 0.01) and lower in the drinkers than in the non-drinkers (drinkers: 4.6 micrograms/dl, non-drinkers: 7.3 micrograms/dl, p less than 0.01). The serum retinol level was not different by smoking habit but was higher in the drinkers than in the non-drinkers (drinkers: 80.4 micrograms/dl, non-drinkers: 67.0 micrograms/dl, p less than 0.01). Serum beta-carotene was higher in the group with a greater intake of vitamin A of vegetable origin (6.1 micrograms/dl) than in the group with a smaller intake of it (4.7 micrograms/dl) (p less than 0.01), but serum retinol was not different by the amount of vitamin A intake of animal food origin. To estimate the respective effects and interactions of the above factors on serum beta-carotene and retinol levels by adjusting for the confounding effects of age, serum total cholesterol, HDL-cholesterol and triglyceride, analysis of covariance was performed. For serum beta-carotene, smoking habit (p less than 0.01), drinking habit (p less than 0.01) and the amount of vitamin A intake of vegetable food origin (p less than 0.05) had significant main effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Characteristics of medical institutions visited by 30 intractable disease patients receiving financial aid for treatment].

In order to determine the characteristics of medical institutions which patients with 30 intractable diseases visited, we analyzed data of a nationwide survey conducted by the Epidemiology of Intractable Diseases Research Committee in 1989. Each of 47 prefectural governments in Japan reported information of all patients with 30 intractable diseases who received financial aid for the diseases between April 1988 and March 1989. Information collected about each patient consisted of identification numbers, which included the disease code, sex, age, the code of the municipality where the patient lived, the medical institution which treated the patient, etc. Out of 173,637 patients whose information was reported by prefectural governments, we used data of 159,910 patients whose medical institutions were reported completely. The results can be summarized as follow: 1) Of the 159,910 patients, 8.6 percent visited medical institutions outside of the prefectures where the patients lived. Many patients living in prefectures located close to large cities, such as Tokyo, visited medical institutions in large cities. 2) The proportion of patients who visited hospitals of medical schools was 27.9 percent. 3) Patients who were affected by diseases causing physical disabilities such as SMON and malignant rheumatoid arthritis tended to visit medical institutions located in their neighborhoods and were treated in small hospitals or clinics. Old patients had the same tendency as patients with such diseases. 4) Although the number of patients receiving aid in 1988, whose data we analyzed in the current study, was larger than that in 1984, the proportion of patients visiting medical institutions outside of the prefecture where the patients lived, and the proportion of patients visiting hospitals of medical schools were nearly equal to those in 1984.

Adolescent↗

Thyroid hormone, L-T3, stimulates the expression of the angiotensinogen gene in cultured opossum kidney (OK) cells.

Angiotensinogen (ANG) messenger RNA is expressed in opossum kidney (OK) proximal tubular cells. To examine whether thyroid hormone, L-T3, could stimulate the expression of the ANG gene in OK proximal tubular cells, fusion genes, consisting of various lengths of the 5'-flanking region of the rat angiotensinogen gene linked to a human growth hormone reporter gene, were constructed and introduced into OK cells. As a negative control, they were introduced into a nonkidney cell line, a human choriocarcinoma cell line (JEG-3). The level of the expression of fusion genes in these cells were determined by the level of immunoreactive human growth hormone secreted into the culture medium. The expression of ANG-growth hormone (ANG-GH) fusion genes pOGH (ANG N-1498/+18), pOGH (ANG N-688/+18), pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), and pOGH (ANG N-35/+18) was 226-, 4.5-, 1.0-, 12-, and 2.5-fold higher than promoterless pOGH in the expression of growth hormone activity in OK cells. No significant expression of any of these ANG-GH fusion genes over the promoterless pOGH was observed in JEG-3 cells. The addition of L-T3 stimulates the expression of pOGH (ANG N-1498/+18) in a dose-dependent manner with a maximal and half-maximal effect at 10(-7) M and at 10(-8) to 10(-9) M, respectively. Thyroid hormone (10(-7) M) also stimulates the expression of pOGH (ANG N-688/+18) but not pOGH (ANG N-110/+18), pOGH (ANG N-53/+18), or pOGH (ANG N-35/+18).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

Primary non-AIDS related brain lymphoma. Patterns of failure following radiotherapy.

Thirteen patients with primary brain lymphoma (PBL) were treated with radiotherapy. Three patients also had ocular involvement with retinal masses at initial presentation. All but one patient received conventional whole brain irradiation and, in addition, spinal irradiation, intrathecal methotrexate or orbital irradiation were given in two, two and four patients respectively. The radiation doses for involved sites ranged from 40 to 65 Gy, and for prophylactic sites from 30 to 50 Gy. After radiotherapy, all patients had complete regression of the tumor on computed tomography. Nine patients relapsed, 5 of them with brain recurrence. Two patients had ocular recurrence exclusively as their first relapse. The remaining two relapsing patients had bone lesions. One patient died intercurrently. As a result, only three patients are alive and free of disease after 16 to 36 months and all three received some adjuvant treatment in addition to whole brain irradiation.

Adult↗