Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 37 records · Page 2Linked to original sources

PubMed1992

A simple elimination of clonogenic tumor cells from human bone marrow in vitro by heat: its application to autologous bone marrow transplantation for B-cell lymphoma.

The application of hyperthermia to the treatment of neoplastic disease has focused on solid tumors. Since the hyperthermic sensitivity of human B-cell lymphoma cells is not known, we have examined the effect of hyperthermia on the growth of B-cell lymphoma cell lines (Raji and Daudi) in vitro to evaluate the ability to purge tumor cells from normal bone marrow by heat, utilizing a limiting-dilution assay to measure log depletion of tumor cells in a 20-fold excess of normal bone marrow. When exposed at 42 degrees C and 43 degrees C for 120 min, both clonogenic Raji and Daudi cells were dramatically decreased (a 4- to 6-log reduction) with exposure time, while leaving over half of the normal granulocyte-macrophage progenitor cells surviving at 42 degrees C and 10% at 43 degrees C. This high level of lymphoma-cell depletion by heat correlated with that obtained in immunologic and pharmacologic studies. These results suggest that in vitro hyperthermia might be applied effectively for the elimination of residual lymphoma cells in autologous marrow grafts before autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma.

Bone Marrow↗

PubMed1992

Pharmacokinetic analysis of antibody localization in human colon cancer: comparison with immunoscintigraphy.

The biodistribution and imaging characteristics of the 111In-labeled anti CEA monoclonal antibody ZCE-025 were studied in five patients with suspicion of colorectal carcinoma. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimen, making a comparison with whole-body imaging with a gamma camera. ZCE-025 localization in tumors was demonstrated by gamma-camera imaging in 4 of the 5 patients, corresponding to surgical findings. Persistent accumulation of 111In in the lymph nodes was observed in one patient, whereas surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon carcinoma. Analysis of individual plasma by size exclusion HPLC showed two radioactivity peaks, labeled antibody and free DTPA. No transchelation of 111In to circulating transferrin was observed. The blood clearance was fitted to a two-compartment equation and its half-lives were found to be 10.8 +/- 8.7 h and 69.5 +/- 21.8 h for t1/2 alpha and t1/2 beta, respectively. Total urinary excretion averaged 0.3% of the injected dose/h with a small patient to patient variation. At 24 hrs postadministration the predominant radiolabeled species in urine was free DTPA. Thereafter, radioactivity in urine was partly present as a low molecular weight catabolic product. No apparent correlation between CEA content and uptake of 111In-ZCE-025 in tumors resected by surgery could be found. How 111In-labeled antibody is accumulated into tumors as well as into some nontumor tissues needs further study.

Aged↗

PubMed1992

Probucol reduces plasma and aortic wall oxysterol levels in cholesterol fed rabbits independently of its plasma cholesterol lowering effect.

To understand further the antiatherogenic mechanism of probucol, the antioxidant effect of this agent was studied on specific cholesterol oxidation products in plasma and aortic wall in equally hypercholesterolemic New Zealand white rabbits. In order to maintain equal plasma total cholesterol levels, five control rabbits (C group) received a 1% followed by a 0.5% cholesterol enriched diet, while the probucol treated rabbits (C+P group) received a graded increase in the cholesterol supplemented diet from 1% to 3%; probucol supplementation was constant at 1%. After 9 weeks of feeding, the plasma oxysterols, cholest-5-ene-3 beta,7 alpha-diol, cholest-5-ene-3 beta,7 beta-diol, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol and 5 alpha-cholestane-3 beta,5,6 beta-triol significantly increased over baseline levels in both experimental groups. However, the increase in all these products in plasma was 20-60% less in the C+P group than the C group (P < 0.05). Furthermore, the C+P aortic wall cholesterol oxide concentrations were 50-90% less than the C group (P < 0.05). The oxysterol pattern of the aortic wall was similar to plasma. Additionally, the aortic wall cholesterol content in the C+P group was 50% less than the C group (P < 0.05). The plasma cholesterol levels were not significantly different at any time point during the study and the cholesterol oxide content in the diets was the same. These results are consistent with the contention that the antioxidant properties of probucol serve as the basis for its antiatherogenic effects in vivo.

Animals↗

PubMed1992

Transient myoclonic state with asterixis in elderly patients: a new syndrome?

We report 7 patients who developed acute co-occurrences of fragmentary generalized myoclonus and asterixis. All patients were elderly and had other chronic diseases. This condition appeared acutely, progressed over several hours and then disappeared in 2-3 days with diazepam administration. No sequelae were noted, although most cases developed recurrences. The myoclonus occurred spontaneously and was slightly enhanced by action. The myoclonus was widely distributed but predominated in the neck, shoulder girdle, and upper extremities. Opsoclonus was not noted. Clinically apparent myoclonus was not evoked by sensory stimuli. Asterixis was observed in the upper extremities in all cases. Asterixis-like movements of the protruded tongue were also observed. Neurological findings other than the myoclonus and asterixis were unremarkable. Neither metabolic nor organic abnormalities clearly responsible for this condition were identified. Cerebral potentials preceding the myoclonic jerks recorded in one case suggested that the myoclonus may have been a spontaneous cortical myoclonus. We named this condition a transient myoclonic state with asterixis (TMA). Awareness of this syndrome is clinically important because of its benign nature, although it can recur.

Aged↗

PubMed1992

Losartan, a specific angiotensin II receptor antagonist, increases angiotensin I and angiotensin II release from isolated rat hind legs: evidence for locally regulated renin-angiotensin system in vascular tissue.

The effect of Losartan (10(-9) to 10(-6) M) on angiotensins I and II release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal and bilaterally nephrectomized rats. Losartan increased dramatically both angiotensins I (Ang I) and II (Ang II) release in a dose-dependent fashion; the maximal percent increment in Ang I and Ang II release evoked by Losartan (10(-6) M) was about +380% and +160%, respectively, in normal rat hind legs. In nephrectomized animals, Losartan elicited a marked increase in both peptides dose-dependently. There was a highly positive correlation between the released amounts of Ang I and that of Ang II altered by Losartan in either normal (r = 0.954) or nephrectomized rats (r = 0.923). These results not only confirm the existence of a functional renin-angiotensin system in vascular tissues, but also suggest that the system is regulated by locally generated Ang II.

Angiotensin I↗

PubMed1992

Effects of losartan, a nonpeptide angiotensin II receptor antagonist, on cardiac hypertrophy and the tissue angiotensin II content in spontaneously hypertensive rats.

Losartan, a recently developed nonpeptide angiotensin II (Ang II) receptor antagonist, was administered orally to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Cardiac weight and tissue Ang II, as well as plasma renin activity (PRA) and Ang II, were determined. Treatment with Losartan (10 mg/kg per day) lowered blood pressure markedly. Losartan reduced significantly the left ventricular weight by 11% compared with control rats. The left ventricular Ang II content was lowered by Losartan (18.6 +/- 0.9 pg/tissue; 21.9 +/- 0.9 pg/tissue, control, p less than 0.05), whereas PRA and plasma Ang II concentration were increased by the treatment. With the control and Losartan-treated animals, there was a significant positive correlation between the left ventricular weight and the tissue Ang II content (r = 0.563, p less than 0.05). These results provide evidence that cardiac tissue Ang II, rather than circulating Ang II, plays an important role in the pathophysiology of left ventricular hypertrophy of this animal model of human hypertension.

Analysis of Variance↗

PubMed1992

Role of the central serotonergic system in the anticonflict effect of d-AP159.

d-AP159 is a d-optical isomer, and in rats it has a high affinity for 5-hydroxytryptamine1A (5-HT1A) receptors and potent anticonflict activity, equal to that of buspirone. The anticonflict effects of d-AP159 and buspirone were investigated in animals in which lesions of the serotonergic neurons were caused by intradorsal raphe (d-RA) injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). The anticonflict effect of buspirone, but not that of d-AP159, was attenuated in 5-HT neuron-lesioned rats. The anticonflict effect of d-AP159 injected into various brain sites was also studied. d-AP159 and buspirone microinjected into the d-RA caused significant anticonflict activity in rats. There was a significant anticonflict effect of d-AP159 injected into the amygdala centralis (ACE), but not the dorsal hippocampus (d-HC). The anticonflict effect of d-AP159 injected into the d-RA was antagonized by systemic administration of (-)propranolol but not Ro 15-1788. This effect of d-AP159 injected into the ACE was antagonized by systematic administration of Ro 15-1788 but not (-)propranolol. These results suggest that the d-RA and the ACE play important roles in the anticonflict effects of d-AP159 but that the mechanisms by which this drug acts at these sites are different.

5,7-Dihydroxytryptamine↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗