[Therapy of chronic myelogenous leukemia].
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Alkylating Agents↗
Biomedical subjects
S Hashimoto
Publications and source records attributed to S Hashimoto.
[Radiation management of retinoblastoma].
Forty-five patients with retinoblastoma were treated at Keio University Hospital from 1970 to 1990. Thirty-two patients had unilateral lesions and 13 had bilateral lesions. Twenty-nine patients with unilateral and 12 with bilateral lesions underwent enucleation for advanced tumor. As a result, 3 patients with unilateral retinoblastoma and all patients with bilateral disease were treated with radiotherapy (40-50 Gy) combined with or without cryotherapy and/or photocoagulation. One patient with unilateral lesion treated with radiotherapy and chemotherapy had metastases at the first visit to our clinic and was excluded from this analysis. Among 16 eyes (15 patients) treated with radiotherapy, 6 eyes had recurrence and needed retreatment. Cataract occurred in 6 of 12 eyes and good vision was preserved in 5 of 10 eyes in which function could be evaluated.
Child, Preschool↗
[Experimental studies on metastases from an irradiated tumor].
This study was carried out to determine the effect of irradiation of a tumor on the development of lung metastases. SANH, a spontaneous sarcoma, was isotransplanted in the right thighs of C3H mice which were either locally preirradiated (30 Gy: TBR) or non-irradiated. When the tumors had grown to 7 mm in diameter, they received 20-30 Gy of electron beams (RTx). The tumor-bearing legs were amputated at various tumor sizes, and the incidence of metastasis and number of lung nodules were compared in each treatment group. The incidences of metastases from 7 mm tumors in mice with regrowing tumors after RTx (30 Gy) and non-irradiated mice were 28% and 4%, respectively. When tumors grown in preirradiated legs were removed at 7 mm in diameter, the incidence of metastases (58%) was also enhanced by preirradiation of the tumor bed. Seven millimeter tumors that were growing in TBR legs and received RTx (20 Gy) developed a higher incidence (82%) and greater numbers of metastases than either the RTx or TBR groups. To determine the relationship between the interval of tumor bearing and development of metastases, tumors were removed at various intervals after tumor transplantation in 4 groups, namely, non-irradiated, TBR, RTx and TBR with 20 GyRTx. Lung metastases came later but increased steeply in mice given either TBR or RTx, compared with non-irradiated mice. Tumors growing in TBR and receiving RTx (20 Gy) developed many more metastases than any other group.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Biased usage of variable and constant-region Ig genes by IgG+, CD5+ human leukemic B cells.
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Antigens, CD↗
Inhibitory effect of inaperisone hydrochloride (inaperisone), a new centrally acting muscle relaxant, on the micturition reflex.
We examined the effects of inaperisone hydrochloride (inaperisone), a new centrally acting muscle relaxant, on bladder function in anesthetized rats and isolated rat tissues. We also investigated its mechanism of action. When a balloon inserted into the bladder was expanded, rhythmic bladder contractions were observed; inaperisone (4 mg/kg i.v.) abolished these contractions, in both normal and decerebrated rats. The bladder tonus or bladder contraction induced by peripheral stimulation of the pelvic nerve was barely inhibited by inaperisone (4 mg/kg i.v.), but this dose of inaperisone abolished the efferent discharge from the pelvic nerve that accompanied the rhythmic bladder contractions. The doses of intracerebroventricularly (i.c.v.) and intrathecally injected inaperisone which abolished the rhythmic bladder contractions were 10 and 100 micrograms, respectively. The inhibitory effects of inaperisone (4 mg/kg i.v.) were not diminished by naloxone (1 mg/kg i.v.) or by bicuculline (0.5 mg/kg i.v.), but were diminished by phaclofen (30 mg/kg i.v. or 300 micrograms i.c.v.). The specific binding of [3H]baclofen to rat brain synaptosomal membranes was barely inhibited by inaperisone (up to 1 mM). From these results, it is speculated that, among other possible mechanisms, inaperisone inhibits the micturition reflex by acting indirectly on GABAB receptors in the brainstem.
Anesthesia↗
[Percutaneous transluminal angioplasty for stenotic dialysis arterio-venous fistulas].
From December 1982 to January 1991, we performed fistulography on 40 patients who complained functional failure of arterio-venous dialysis fistula. And percutaneous transluminal angioplasty (PTA) was attempted on 15 patients (19 times) who revealed marked fistula stenosis. Initial successful rate was 78.9% and patency rate was 56.2% in the first 6 months. (75% in the first 6 months when angioplasty was initially successful). We describe the method of fistulography and PTA for stenotic dialysis fistulas, and evaluate the usefulness of PTA. And also we introduce our attempts for improving the initial successful rate and patency rate. In conclusion, when dialysis arterio-venous fistula is stenotic but not occlusive, PTA should be considered first before surgical treatment is done.
Adult↗
Neurogenic responses of urethra isolated from the dog.
Electrical transmural stimulation evoked contraction and relaxation in isolated urethral circular muscle of the dog. The responses were abolished by tetrodotoxin, indicating their neurogenic origin. The contractile force in the middle urethra was greater than that in the proximal and distal urethra. The contractions were not affected by atropine and propranolol, but were completely inhibited by phenoxybenzamine, prazosin and guanethidine. In preparations contracted with prostaglandin F2 alpha, electrical stimulation induced frequency-dependent relaxation in all urethral portions. Atropine, phenoxybenzamine, prazosin and guanethidine had no effect on the relaxation, while propranolol slightly attenuated the relaxation induced at the highest frequency used (5 Hz). The non-adrenergic, non-cholinergic relaxation was also not affected by ketanserin, methysergide, diphenhydramine, alpha,beta-methylene ATP or capsaicin. Exogenously applied phenylephrine and clonidine both produced contractions but the maximal response to clonidine was much smaller than that to phenylephrine. Acetylcholine produced no or feeble contractions. In the preparations contracted with prostaglandin F2 alpha, isoproterenol and vasoactive intestinal polypeptide (VIP) produced relaxation. These results suggest that the circular muscle of dog urethra is reciprocally innervated by sympathetic adrenergic and non-adrenergic, non-cholinergic nerves, and that the neurogenic responses are markedly affected by muscle tension and the portion of the urethra examined.
Animals↗
Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6.
NF-IL6 was originally identified as a DNA binding protein regulating interleukin-1 (IL-1)-stimulated IL-6 expression. Direct cloning of NF-IL6 showed its homology with C/EBP, a hepatocyte- and adipocyte-specific transcription factor. This study showed that the expression of NF-IL6 messenger RNA (mRNA) increased markedly during the differentiation to a (mRNA) increased markedly during the differentiation to a macrophage lineage in mouse myeloid leukemia cells M1, human histiocytic leukemia cells U937, promyelocytic leukemia cells HL-60, and human peripheral monocytes. Particularly in HL-60 cells that undergo granulocyte or macrophage differentiation depending on inducers, NF-IL6 mRNA was specifically upregulated during macrophage differentiation but not granulocyte differentiation. It was also shown that the functional NF-IL6 protein increased during the differentiation of U937 cells. Furthermore, recombinant NF-IL6 was found to bind to the regulatory regions of the IL-1, tumor necrosis factor, granulocyte colony-stimulating factor, and lysozyme genes, which are expressed in mature macrophages. These results suggest that NF-IL6 may possibly be involved as an important transcription factor in the process of activation and/or differentiation of macrophages.
Animals↗
Possible model for generation of P9 far-field potentials.
The distribution of P9 far-field somatosensory evoked potentials, after stimulation of the median nerve with a knee reference, was examined to determine the mechanism of the generation of P9 potentials. In addition to positive potentials (P9s), we found a negative potential (N9) recorded from the chest ipsilateral to the stimulation. The simulation of the distribution of these P9/N9 potentials by an electrical circuit diagram suggested the validity of this model for generation of the P9s.
Electric Stimulation↗
Cumulative white matter changes in the gerbil brain under chronic cerebral hypoperfusion.
An animal model of chronic brain hypoperfusion has been developed by applying coiled clips to the bilateral carotid artery of Mongolian gerbils. The brain tissue damage was neuropathologically studied after 1, 4, 8, and 12 weeks of hypoperfusion. The hippocampus, basal ganglia, and cerebral cortex of the chronically hypoperfused gerbil showed lesions with various severity which are probably due to ischemic episodes. In the cerebral white matter, however, two types of lesions were observed; one similar to those in the gray matter, and the other observed only in the white matter after more than an 8-week duration of brain hypoperfusion. The lesion specific to the white matter showed rarefaction and gliosis without locally associated ischemic changes. This type of the white matter lesion was never found in the gerbil brain before 8 weeks and, significantly, increased in number and size by 12 weeks post operation. The accumulation of the white matter lesions is characteristic in the gerbil with chronic hypoperfusion. The observed white matter-specific lesion resembles the histological changes in aged brain with cerebrovascular diseases.
Animals↗
Transcatheter hepatic arterial chemoembolization using epirubicin-lipiodol: experimental and pharmacological evaluation.
The experimental and pharmacological characteristics of various formulations of an anticancer agent (epirubicin, EPI) and lipiodol were evaluated in vitro and in vivo. Three forms of EPI-lipiodol, i.e., an oil-in-water type of emulsion (O/W type), a water-in-oil type of emulsion (W/O type), and a suspension (S type), were prepared and investigated for their stability. An O/W-type emulsion using a stock solution of Iopamidol as the solvent for EPI was the most stable form in the stationary state in vitro. In 16 patients with malignant liver tumors (14 hepatocellular carcinomas and 2 liver metastases), the three forms of EPI-lipiodol were injected into the proper hepatic artery. The plasma EPI level was monitored periodically and analyzed pharmacokinetically. No significant difference in the pharmacokinetics of EPI was detected among the O/W, W/O, and S types.
Aged↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗