Evidence against a seronegative HTLV-I carrier rate among children.
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Adolescent↗
Biomedical subjects
M Nakashima
Publications and source records attributed to M Nakashima.
Mouse-human chimeric monoclonal antibody to carcinoembryonic antigen (CEA): in vitro and in vivo activities.
Mouse-human chimeric antibody specific for human carcinoembryonic antigen (CEA) was produced by recombinant DNA techniques. The genes of the mouse variable regions of heavy and light chains were cloned from the mouse hybridoma, 2.7.1G.10., which secreted anti human CEA antibody (IgG1, kappa), and were joined with human gamma 1 and kappa constant genes. The affinity of the resultant chimeric antibody to its relevant antigen was the same as that of the parental mouse monoclonal antibody when analysed by Scatchard plot analysis. The chimeric antibody showed a potent antibody dependent cell-mediated cytotoxicity (ADCC) activity with human peripheral blood mononuclear cells against CEA-positive human adenocarcinoma cells. In vivo imaging analysis revealed that the present chimeric antibody was specifically localized on the tumor site. These results indicate that our mouse-human chimeric antibody is a promising reagent for the diagnosis and therapy of CEA-positive human cancers.
Amino Acid Sequence↗
Selective IgG deficiency with a transcriptional disorder of the gamma switching region gene and the IL-4 gene.
A primary immunodeficiency patient was analysed whose serum IgG and IgE were extremely low but whose IgM and IgA levels were within the normal range or elevated. Southern blot analysis indicated no deletion of structural genes coding for C gamma, C epsilon, or C alpha. The majority of the patient's peripheral B cells expressed IgM and IgD on the surface yet IgG-positive B cells were not detected, suggesting that the defect is in a switch-recombination process from IgM to IgG. The RFLP pattern detected with the S mu and S gamma DNA regions revealed that there was no deletion or large mutation in the switch region DNA. An in vitro IgG production system with pokeweed mitogen showed an abnormality at the transcriptional level and the defects were in both the patient's T and B cells. Addition of recombinant IL-4 (rIL-4) to the normal B cells enhanced IgG production but the patient's B cells did not respond to rIL-4, although the IL-4 receptor was present at the normal level. Messenger RNA and IL-4 protein were not produced in the patient's T cells upon stimulation with phorbol ester and calcium ionophore, whereas IL-2 was normally produced. The patient's lymphocytes showed a proliferative response to various mitogens, including phorbol ester. The transcripts of unrearranged C gamma region genes were not detected in the patient's lymphocytes, suggesting that the chromatin structure of the S gamma region may not be open. These results suggest that the transcriptional defects at the S gamma region gene in B cells and at the IL-4 gene in the T cells may be responsible for the present IgG immunodeficiency. There might be a common transcriptional system operating in a certain step in the activation of both genes.
Adult↗
Comparative effects of antidepressants, amitriptyline, and maprotiline on intraventricular conduction, effective refractory period, and incidence of ventricular arrhythmias induced by programmed stimulation in dog hearts after myocardial infarction.
The effects of amitriptyline and maprotiline, standard tricyclic and tetracyclic antidepressants, on intraventricular conduction, the effective refractory period (ERP), and the incidence of ventricular arrhythmias induced by programmed stimulation were studied and compared in dog hearts after myocardial infarction. Amitriptyline at doses of 1-3 mg/kg significantly slowed ventricular conduction of the infarcted zones in a frequency-dependent and dose-dependent manner. Amitriptyline at doses of 2 and 3 mg/kg slowed conduction slightly in normal zones. The ERP was prolonged by amitriptyline at a dose of 2 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. Maprotiline at doses of 1-3 mg/kg slowed conduction in infarcted zones to a lesser extent as compared with amitriptyline, although severely depressed conduction in the infarcted zone was obviously slowed by maprotiline. Maprotiline did not increase the incidence of ventricular arrhythmias significantly. From the present results, maprotiline appears to have less cardiac toxicity than amitriptyline, although maprotiline produces a slight decrease in conduction of infarcted zones.
Action Potentials↗
The measurement of haloperidol and reduced haloperidol in hair as an index of dosage history.
1. We report a method for measuring the concentrations of haloperidol (HL) and its major active metabolite, reduced haloperidol (RHL), in human scalp hair. 2. Hair samples were obtained from 59 patients who had been taking HL at fixed daily doses for more than 4 months and whose compliance was good. A morning pre-dose plasma sample was also obtained from 48 of these patients. 3. The concentrations of HL and RHL in hair (ng mg-1 hair) correlated significantly both with the daily dose (micrograms kg-1 body weight) of HL (r = 0.682, P less than 0.001 for HL and r = 0.813, P less than 0.001 for RHL, n = 59) and with the trough concentration (ng ml-1) of the corresponding compound in plasma at steady state (r = 0.558, P less than 0.001 for HL and r = 0.563, P less than 0.001 for RHL, n = 48). The correlation coefficients were slightly higher using the sum of the concentrations of both substances in hair (r = 0.829 for the correlation with daily dose and r = 0.609 for that with trough concentration). 4. Hair from other patients, in whom the dosage of HL had been changed within a few months prior to sampling, was sectioned into 1 cm-long portions successively from the roots and the concentrations of both compounds in each portion were measured. Assuming a growth rate of 1-1.5 cm/month, a history of individual dosage could be deduced in all patients from the distribution of the drug and metabolite along the single hair length.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Alterations of responsiveness to adrenoceptor agonists and calcium of non-infarcted hypertrophied muscles from rats with chronic myocardial infarction.
1. The responsiveness of hypertrophied right ventricular muscle from rats with chronic myocardial infarction (MI) was examined. Myocardial infarction was produced by ligating the left coronary artery. The positive inotropic effects of alpha- and beta-adrenoceptor agonists and calcium on the isolated non-ischaemic muscles were determined at one and four weeks after ligation, and were compared with those in sham-operated (SO) rats. 2. The contractile force of electrically-driven right ventricular papillary muscles was measured isometrically. We also determined the change of beating rate of the right atrium in response to a beta-adrenoceptor agonist. 3. Basal contractile force increased at four weeks after ligation. 4. The pEC50 values of the alpha 1-adrenoceptor agonist, methoxamine, and calcium increased at four weeks after ligation, but the pEC50 values of the beta-adrenoceptor agonist, dobutamine did not change. 5. Maximal contractile force did not change with these agonists at either one and four weeks after ligation. 6. Tissues from rats four weeks after MI exhibited slight increases in the Bmax of alpha- but not beta-receptors, without any changes of affinity. 7. The increases in the sensitivity to an alpha 1-adrenoceptor agonist and calcium may be compensatory mechanisms of non-infarcted ventricular tissue which has undergone hypertrophy in chronic MI.
Adrenergic alpha-Agonists↗
Pinacidil inhibits neuromuscular transmission indirectly in the guinea-pig and rabbit mesenteric arteries.
1. Effects of pinacidil were investigated on neuromuscular transmission in smooth muscle tissues of the rabbit and guinea-pig mesenteric arteries by both electrophysiological procedures and a bioassay of noradrenaline (NA) outflows. 2. Pinacidil (over 1 microM) hyperpolarized smooth muscle cell membranes in both tissues, in a concentration dependent manner. Pinacidil hyperpolarized and increased the ionic conductance of smooth muscle membrane more markedly in the rabbit mesenteric artery than in the guinea-pig. The hyperpolarization induced by pinacidil occurred in the presence or absence of endothelial cells and was blocked by glibenclamide. 3. Perivascular adrenergic nerve stimulation produced excitatory junction potentials (e.j.ps) and repetitive stimulation produced a facilitation of e.j.ps in both tissues. Pinacidil (over 1 microM) reduced the amplitude and the decay time of e.j.ps to a consistently greater extent in the rabbit mesenteric artery than in the guinea-pig. However, the facilitation process of e.j.ps was not modified following application of pinacidil (1 microM). The pinacidil-induced inhibition of e.j.ps was prevented by pretreatment with glibenclamide. 4. Pinacidil (30 microM) marginally increased the overflows of NA and its metabolite, 3,4-dihydroxyphenylglycol (DOPEG) released following repetitive perivascular nerve stimulations. 5. Pinacidil (10 microM) partly inhibited the voltage-dependent Ca channel, as estimated from the recovery process following removal of pinacidil, of action potentials evoked on e.j.ps. 6. It is concluded that pinacidil increases ionic conductance and hyperpolarizes smooth muscle cell membranes of the guinea-pig and rabbit mesenteric arteries and as a consequence, inhibits the neuromuscular transmission process occurring on adrenergic nerve stimulation with no reduction in the amount of released transmitter.
Animals↗
Effect of arachidonic acid on the inner ear blood flow measured with a laser Doppler flowmeter.
The present study was undertaken to clarify the effect of arachidonic acid (AA) on the inner ear blood flow of rats as measured with a laser Doppler flowmeter. With the rats under anesthesia with sodium pentobarbital, the middle ear was approached ventrally and a laser Doppler probe was positioned over the lateral wall of the cochlea. Drugs were administered via the subclavicular artery. The dose range of each drug was determined so as not to affect the systemic blood pressure. The AA (20 to 70 micrograms) increased the inner ear blood flow dose-dependently; this effect was abolished by indomethacin (5 mg orally). Both prostaglandin E2 (PGE2; 1 to 50 ng) and CS-570, a PGI2 analogue (12.8 to 25.6 ng) caused a dose-dependent increase in the inner ear blood flow. The response of PGI2 was shorter than that of PGE2. On the other hand, a stable thromboxane A2 (STA2; 30 to 80 ng) decreased the inner ear blood flow dose-dependently. Administration of PGF2 alpha (0.2 to 3 micrograms) showed no effect on the inner ear blood flow. These results indicated that the effect of AA was mediated mainly via PGI2 and PGE2.
Animals↗
[A phase III study of KRN 8601 (rhG-CSF) on neutropenia induced by chemotherapy for malignant lymphoma--a multi-institutional placebo controlled double-blind comparative study].
The clinical usefulness of KRN 8601 (rhG-CSF) was evaluated in patients with neutropenia induced by chemotherapy for non-Hodgkin lymphoma in a double-blind study. The same chemotherapeutic regimens repeated for twice in 3 to 4 weeks interval. During the first cycle of chemotherapy, changes of leukopenia (neutropenia) were observed, and KRN 8601 at a dose of 75 micrograms/body or placebo was started to administer subcutaneously 72 hours after the termination of the second cycle and continued for 14 days. Elevations of nadirs of absolute neutrophil counts (ANC) and significant shorting of neutropenic periods of ANC below 2,000/mm3 were observed with patients given KRN 8601. KRN 8601 is significantly superior over placebo (p less than 0.0001), while overall safety evaluation showed no significant difference between the two groups. All the above results indicate that KRN 8601 is extremely usefull for the neutropenia induced by chemotherapy.
Adult↗
Effect of an aldose reductase inhibitor on altered sympathetic nerve responsiveness of isolated right atria in diabetic rats.
1. To determine the effects of an aldose reductase inhibitor (ARI) on diabetes-induced cardiac sympathetic disturbance, the effects of (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene] rhodamine (ONO-2235), an aldose reductase inhibitor, as well as insulin on the responsiveness to the transmural sympathetic nerve stimulation (TNS) and norepinephrine (NE) of isolated right atria of streptozotocin-induced diabetic rats were investigated. 2. The responsiveness to TNS of 8-week diabetic rats decreased, and those of 12-week diabetic rats severely decreased. The responses to NE also decreased 8 weeks or more after the induction of diabetes. 3. In 8-week diabetic rats, the insulin treatment completely restored the responsiveness to TNS, while ARI treatment partially restored the responsiveness to TNS. In 12-week diabetic rats, the single treatment with insulin or ARI only slightly restored the responsiveness to TNS, while the combination treatment with insulin and ARI almost completely restored the responsiveness to TNS in 12-week diabetic rats. 4. From the present results, the following may be concluded: Sympathetic nerve responses of right atria decreases in diabetic rats, and these changes may be related to hypoinsulinemia and abnormal polyol pathway. Although a serious sympathetic disturbance was only slightly improved by insulin or ARI, the combination of insulin and ARI produced more remarkable improvement of this disturbance.
Aldehyde Reductase↗
[The emotional reaction on other child patients caused by the crying of the uncooperative child patient].
The subjects were a total of 60 children, of which 30 were kindergarteners, and 30 were school age children. Changes in internal behavior were observed when the subjects were stimulated by only visual stimulation (V), only audio stimulation (A) and audio-visual stimulation (AV) of the crying of other child patients for 20 seconds each. The change ratios of the 3 stimuli were analyzed with respect to the plethysmogram (PL), the respiration curve (RC) and the galvanic skin reflex (GSR). The internal changes to the 3 stimuli of the crying were compared with difference in stimulus, age difference, sex difference, the difference of dental anxiety. 1) The change ratios decreased in the following order, AV greater than A greater than V on PL and RC. There were significant differences between V and A, also V and AV on PL and GSR. Based on the standardized score, the score decreased in the following order, AV greater than A greater than V, and there were significant differences between V and A, also V and AV. 2) Comparing age groups, kindergarteners showed larger change ratios than school age children for A and AV by GSR. Based on the standardized score, there were no significant age difference for each stimulation. 3) Comparing sex groups, there was a significant difference for A by PL. According to the standardized score, there was no significant sex difference for each stimulation. 4) There was no significant difference for each stimulation by the dental anxiety degree of the mother.
Age Factors↗
[Comparisons of meter reading values in 5 electronic measuring devices].
The root apex values given in the manufacturers' introductions of 5 electronic measuring devices were compared with the mean values measured by each device in the following cases: a) The tip of file was at the apical constriction in the experimental tooth model. b) The tip of file was between 0 mm and -2.0 mm from the root apex in the vital teeth and the pulpless teeth. In the experimental tooth model, when the tip of file was at the apical constriction, the mean values measured by each device except EM were lower than the root apex values given in the manufacturers' introductions of each device. In the case of the vital tooth, when the tip of file was between 0 mm and -2.0 mm from the root apex, the mean values measured by EM-S II and EM were similar to the values given in the manufacturers' introductions of these devices, but not to those obtained by the other devices. Measurements of the pulpless tooth by each device revealed mean values lower than the values given in manufacturers' introductions for the root apex.
Dental Pulp Cavity↗
[Oral findings of institutionalized handicapped children].
In this study, we investigated the oral conditions of 77 handicapped children (57 boys and 20 girls) and backgrounds of living in an institution. The results were as follows. Among 73 children having permanent dentition, the percentage of subjects with one or more DMF teeth was 94.52%, while DMFT was 7.45. The percentage of teeth treated for dental caries was 57.35%. GI (Gingival Index) was 1.7, and OHI-S was 3.50. The other features observed were attrition of posterior teeth in 25 subjects and crowding in 39. According to the degree of mental retardation, severely retarded children had a lower percentage of teeth treated for dental caries than moderately and mildly retarded children. Additionally, the severely retarded handicapped children who were long-time institutionalized and taking antispastic drugs, had the higher incidence of gingivitis and poor oral hygiene. This study indicated the necessity of a scheduled and active practice in order to improve oral hygiene status and gingival condition, and raise the percentage of teeth treated for dental caries of severely retarded children in an institution.
Child↗
Effects of an aldose reductase inhibitor, ONO-2235, insulin and their combination on the altered responsiveness to the nerve stimulation and agonists of the isolated atria of diabetic rats.
To determine the effects of an aldose reductase inhibitor (ARI) on diabetes-induced cardiac autonomic nerves disturbance, we examined the effects of ONO-2235, an ARI, as well as insulin on the responsiveness to the nerve stimulation and agonists of the isolated atria of the streptozotocin-induced diabetic rats. Insulin, 4 U/animal/day, was administered s.c. for 4 weeks before the experiment and ARI (ONO-2235), 40 mg/kg/day, was administered p.o. 3 weeks before the experiment. The transmural nerve stimulation (TNS) of sympathetic nerves and parasympathetic nerve was performed in the presence of atropine and metoprolol plus prazocin, respectively. The positive chronotropic and the inotropic responses of the atria to sympathetic TNS and to norepinephrine decreased in the rats diabetic for 8 and 12 weeks. In the rats diabetic for 8 weeks, the insulin treatment restored completely both the positive chronotropic and the inotropic responses to sympathetic TNS, whereas the ARI treatment partially improved the positive chronotropic response and did not improve the positive inotropic response. In the rats diabetic for 12 weeks, the insulin treatment partially improved the positive chronotropic and the inotropic responses to sympathetic TNS, whereas the ARI treatment only slightly improved the positive chronotropic response and did not improve the positive inotropic response to TNS. The combination treatment with insulin and ARI restored completely both the positive chronotropic and the inotropic responses in the rats diabetic for 12 weeks. In rats diabetic for both 8 and 12 weeks, the decreased positive chronotropic and the inotropic responses to norepinephrine recovered completely with the insulin treatment, but did not with the ARI treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Aldehyde Reductase↗
Characterization of cells cultured from human giant-cell tumors of bone. Phenotypic relationship to the monocyte-macrophage and osteoclast.
Cell culture techniques were used to clarify the histogenesis of giant-cell tumor of bone. Even after passage, nearly all of the mononuclear cells possessed tartrate-resistant acid phosphatase and receptors for eel calcitonin, which are both phenotypic markers for osteoclasts. Eel calcitonin produced an increase in the cyclic adenosine monophosphate (cAMP) content of the mononuclear cells. More than 90% of mononuclear tumor cells expressed monocyte markers; flow cytometric C3b receptor, a macrophage marker, was also detected in a few cells. These findings demonstrate that the mononuclear cells expressed phenotypes of both the osteoclast and monocyte-macrophage and that they originate in a monocyte-macrophage-osteoclast lineage. Giant-cell tumor of bone may thus provide a good model for investigating the mechanism of bone resorption in which cells of osteoclast lineage play a central role.
Biomarkers↗
Increases in alpha-but not beta-adrenoceptors in hypertrophied non-infarcted cardiac muscles from rats with chronic myocardial infarction.
The alteration in adrenoceptors in the hypertrophied right ventricle of the rats with myocardial infarction (Ml) was examined. The density of alpha-1-adrenoceptors increased in four and twelve week old Ml rats but not in one week old Ml rats. The beta-adrenoceptors did not significantly change. It is probable that the increased density of alpha-adrenoceptors may be one of the causes for the increased responsiveness to the alpha-adrenergic agonist in the hypertrophied cardiac muscles of Ml rats.
Animals↗
[Clinical utility of long-term administration of trapidil (MDR-1865) in the treatment of diabetic retinopathy].
In order to investigate the usefulness of prolonged administration of trapidil in the treatment of diabetic retinopathy, a follow-up study was carried out after the end of a placebo-controlled, double-blind study of the drug in case of the trapidil-treated group who continued to be treated with 300 mg/day of trapidil (Rocornal) (TT group) and those of the placebo group who were not given any treatment after the end of the study (PP group). The TT group was significantly superior or tended to be superior to the PP group in improvement of hard exudates, retinal hemorrhages and soft exudates, and also in improvement of capillary microaneurysms on fluorescein fundus angiography. In the course of diabetic retinopathy by the global evaluation of findings in individual cases, the TT group was significantly superior or tended to be superior to the PP group. Photocoagulation was performed on 20 (28%) of 72 eyes of the PP group and 13 (19%) of 68 eyes of the TT group, with the mean interval to photocoagulation being 7.2 months for the PP group and 14.0 months for the TT group. There was a significant difference between the 2 groups in terms of the interval to photocoagulation. Randomized fundus photographic evaluation of the findings by the central evaluation committee showed that the TT group was significantly superior or tended to be superior in improving retinal hemorrhages, soft exudates and leakage of fluorescein dye, and was also significantly superior or tended to be superior in relation to the course of the retinopathy, which was consistent with the evaluation by the attending ophthalmologists.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Merits and demerits of long acting formulation of cardiovascular drugs].
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Administration, Cutaneous↗