Epstein-Barr virus-associated CD3- large granular lymphocyte leukemia presenting with polycranial nerve palsies.
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Adult↗
Biomedical subjects
Y Ohno
Publications and source records attributed to Y Ohno.
Contrasting effects of SM-9018, a potential atypical antipsychotic, and haloperidol on c-fos mRNA expression in the rat striatum.
SM-9018 (cis-2-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl) hexahydro-1 H-isoindole-1,3(2H)-dione HCl) is a potential atypical antipsychotic with high affinity for 5-HT2, dopamine D2 and 5-HT1A receptors. Northern blot analysis was performed to compare the effects of SM-9018 and of haloperidol on the striatal c-fos mRNA expression in rats. Haloperidol (0.3-30 mg/kg, p.o.) markedly increased the striatal c-fos mRNA levels (about eight-fold at 30 mg/kg), the increase being abolished by lesioning of dopamine neurons with 6-hydroxydopamine. In contrast, SM-9018 produced only a slight increase (about two-fold) in c-fos mRNA expression at doses up to 30 mg/kg (p.o.). The 5-HT2 receptor antagonist, ritanserin (0.1-3 mg/kg, i.p.), dose-dependently attenuated the haloperiodol-induced c-fos expression, but the putative 5-HT1A receptor antagonist, NAN-190 (1-(2-methoxyphenyl)-4-(4-(2-phethalimmido)butyl)piperazine HBr; 1-10 mg/kg, i.p.), did not. These findings suggest that SM-9018 is weaker than haloperidol for induction of striatal c-fos mRNA expression, to which the 5-HT2 receptor blocking activity of SM-9018 seems to contribute.
Animals↗
Newly developed ST-T abnormalities on the electrocardiogram and chronologic changes in cardiovascular risk factors.
An ST-T abnormality on an electrocardiogram (ECG) is known to independently predict subsequent morbidity and mortality from cardiovascular diseases. But how ST-T abnormality develops in relation to chronologic changes in cardiovascular risk factors has not been fully discussed. Sixty-eight men whose ECG had been initially normal but who exhibited ST-T abnormality later (ST-T subjects) were identified among 21,579 apparently healthy adults who had undergone comprehensive health examinations for > 10 years. Echocardiography proved that 26 of 29 examinees among ST-T subjects had left ventricular hypertrophy. Antihypertensive drugs were given to 26 of the ST-T subjects. Their cardiovascular risk factors were chronologically reviewed from 10 years before the onset of definite ST-T abnormality, and were compared with those of 68 men whose ECG had remained consistently normal for 10 years (controls). Mean values of systolic and diastolic blood pressure gradually increased over 10 years (from 127/78 to 144/84 mm Hg) among ST-T subjects, but showed little change (from 122/76 to 124/77 mm Hg) during the same period in controls. The time course of blood pressure over 10 years was similar in ST-T subjects, irrespective of final blood pressure level. Mean serum cholesterol and glucose increased over 10 years in both ST-T and control subjects. Uric acid decreased over 10 years (from 6.1 to 5.6 mg/dl) only in ST-T subjects. Multivariate analysis revealed that blood pressure and uric acid before onset of ST-T abnormality were chronologically changed independent of other risk factors. The time course of risk factors may be of great importance in the development of cardiovascular disorders.
Blood Pressure↗
Dopamine and 5-hydroxytryptamine selectively potentiate neuronal type ATP receptor channels.
Dopamine and 5-hydroxytryptamine have been shown to facilitate a cationic current activated by extracellular ATP in rat pheochromocytoma PC12 cells. Effects of these and other modulators were examined by expressing ATP receptor channels in Xenopus oocytes using cDNAs from rat vas deferens ('P2x1-purinoceptor channels') and PC12 cells ('P2x2-purinoceptor channels'). Dopamine and 5-hydroxytryptamine (10 and 100 mu M) facilitated the ATP-activated current mediated through P2x2-purinoceptor channels, but not the current through P2x1-purinoceptor channels. Adenosine (1 mu M) facilitated the current through both P2x1- and P2x2-purinoceptor channels. Cd2+ (1 mM) as well as Zn2+ (10 mu M) selectively potentiated the current through P2x2-purinoceptor channels. The results suggest that (1) the facilitation by dopamine and other modulators also occurs in recombinant ATP-receptor channels, and (2) the selective facilitation by dopamine, 5-hydroxytryptamine and divalent cations of P2x2-purinoceptor channels is attributed to some structural difference of the channels from P2x1-purinoceptor channels.
Adenosine Triphosphate↗
Teratogenic effects of selenium compounds on cultured postimplantation rat embryos.
Embryonic susceptibility to selenium (Se) teratogenicity was examined in rats using postimplantation embryo culture. Rat embryos at day 9.5 of gestation were cultured by the roller bottle method for 48 hr in the presence of Se compounds. Sodium selenite, sodium selenate, seleno-DL-methionine, and seleno-DL-cystine were embryolethal at 20, 300, 1,000, and 1,000 microM Se, respectively. All of these compounds caused abnormalities such as deformed optic vesicle and swollen rhombencephalon in the viable embryos. These abnormalities were considered to correspond to in vivo malformations caused by Se in hamster fetuses or in bird embryos. These results indicate that rat embryos are susceptible to Se teratogenicity. It seems that there are differences in potency ranking of Se compounds between rat and bird embryos.
Abnormalities, Drug-Induced↗
Granulocyte colony-stimulating factor-induced mobilization of peripheral blood stem cells for autologous and allogeneic transplantation. Fukuoka Bone Marrow Transplantation Group.
Peripheral blood stem and progenitor cells (PBSC and PBPC), which circulate at very low levels during steady-state hematopoiesis, show a transient but marked increase during hematologic recovery from marrow-suppressive chemotherapy. To ensure rapid and sustained hematologic engraftment after autologous PBSC transplantation, sufficient PBSC or PBPC must be infused. To confirm the utility of granulocyte colony-stimulating factor (G-CSF) in chemotherapy-induced PBSC mobilization, we investigated the effect of G-CSF on PBSC mobilization in leukemia and lymphoma patients. The study design was such that PBSC mobilization with and without G-CSF was assessed in the same patients. The results indicate that PBSC mobilization can be enhanced significantly when G-CSF is given during the recovery phase postchemotherapy. Interestingly, progenitor cells of different lineages could be mobilized by G-CSF. We subsequently investigated the effect of increasing G-CSF dose on PBSC mobilization during steady-state hematopoiesis in healthy adult donors. The results indicate that not only committed but also primitive progenitor cells are mobilized into the circulation in a dose-and time-dependent manner when G-CSF at 5, 10, or 15 micrograms/kg was given on each of 5 days and leukapheresis was performed on day 6. From our data we estimate that sufficient PBSC for engraftment after allogeneic PBSC transplantation can be collected on day 5 of administration of G-CSF at 10 micrograms/kg and by 10-1 leukapheresis on days 5 and 6. Furthermore, we found that some G-CSF-mobilized PBSC retained their self-renewal capability. These observations suggest that hematopoietic stem cells for allogeneic PBSC transplantation can be mobilized by short-term administration of relatively high-dose G-CSF.
Animals↗
Solution conformations of KNI-272, a tripeptide HIV protease inhibitor designed on the basis of substrate transition state: determined by NMR spectroscopy and simulated annealing calculations.
KNI-272, a highly selective and potent HIV protease inhibitor containing allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid], named Apns, has been studied in dimethylsulfoxide-d6 by NMR spectroscopy and simulated annealing calculations. 1H and 13C spectra showed the presence of two conformers characterized by the configuration of the imide bond between the Apns and Thz residues, i.e., trans and cis forms, respectively. Rotating frame Overhauser effect spectra revealed that the trans conformer is dominant. The solution structure calculated from the distance information resulting from nuclear Overhauser effects experiments is similar overall to those observed in the solid states, either as a single crystal or as complex with the protease. The results from both molecular dynamics simulations and experimental 13C longitudinal relaxation times indicate that the backbone of KNI-272 has a fairly rigid conformation.
Crystallography, X-Ray↗
Effects of SM-9018, a novel 5-HT2 and D2 receptor antagonist, on electrically-evoked [3H]acetylcholine release from rat striatal slices.
1. Electrical stimulation (1 Hz) of striatal slices evoked Ca(+2)-dependent [3H]ACh release, which was inhibited by the D2 agonist quinpirole (QPL). 2. SM-9018 and other neuroleptics antagonized the QPL-induced inhibition of the evoked [3H]ACh release. The relative potencies of the neuroleptics in antagonizing the QPL action were nemonapride > haloperidol approximately equal to SM-9018 > > chlorpromazine > > SCH 23390, and the rank order, except for nemonapride, was consistent with their binding affinities to striatal D2 receptors. 3. SM-9018 was weaker than haloperidol in enhancing the [3H]ACh release evoked by higher frequency (3 Hz) stimulation, the enhancement being abolished by the depletion of endogenous dopamine with reserpine pretreatment. 4. The selective 5-HT2 antagonist LY 53857 significantly attenuated the stimulatory effects of haloperidol on the 3 Hz-evoked [3H]ACh release. 5. These findings suggest that SM-9018 is as potent as haloperidol in antagonizing the QPL action on [3H]ACh release at striatal D2 receptors, but is weaker than haloperidol in enhancing the [3H]ACh release under high-frequency stimulation. The 5-HT2 blocking activity of SM-9018 seems to be involved in the latter effects.
Acetylcholine↗
Serum levels of soluble interleukin-2 receptor in patients with perennial allergic rhinitis before and after immunotherapy.
BACKGROUND: Interleukin-2 receptor (IL-2R) exists in soluble form in sera, and the rate of release of the soluble form of IL-2R (soluble IL-2R) reflects T cell activation in vivo. Since T lymphocytes play a central role in respiratory allergic disorders, the measurement of serum levels of soluble IL-2R may be useful in analyzing the disease state of allergic disorders. OBJECTIVE: To investigate the serum concentrations of soluble IL-2R in 48 patients with perennial allergic rhinitis and 14 nonatopic healthy controls, with special reference to the possible changes following long-term immunotherapy. METHODS: This retrospective study included 48 patients who had had variable periods of long-term immunotherapy with Dermatophagoides farinae extracts. The duration of immunotherapy ranged from 5 to 15 years. Serum samples were collected twice from each patient, before the initiation of immunotherapy and at the time of clinical assessment of immunotherapy. All the serum samples were simultaneously used for determination of soluble IL-2R concentrations, by the use of an enzyme-linked immunosorbent assay. To serve as controls, 14 nonallergic subjects of the same age range and sex were chosen. RESULTS: Patients with allergic rhinitis before immunotherapy had significantly higher serum levels of soluble IL-2R than nonatopic subjects. Elevated serum levels of soluble IL-2R decreased significantly following immunotherapy and the serum levels of soluble IL-2R in patients with allergic rhinitis after immunotherapy were not statistically different from those of nonatopic subjects. In addition, the percent decrease in serum soluble IL-2R correlated significantly with the duration of immunotherapy. CONCLUSIONS: Hyperactivity of helper T cells of atopic patients is altered after long-term immunotherapy, and such immunoregulatory changes could be theoretically involved in the mechanisms of immunotherapy.
Adolescent↗
Generation of human natural killer cells from peripheral blood CD34+ cells mobilized by granulocyte colony-stimulating factor.
We studied the generation of human natural killer (NK) cells from CD34+ cells that were isolated from peripheral blood stem cells (PBSC) mobilized by granulocyte colony-stimulating factor (g-CSF). The isolated CD34+ cells were cultured in the presence of a combination of interleukin-1 (IL-1alpha), IL-2, and stem cell factor for 5 weeks without marrow stroma. We found that the CD34+ cells isolated from G-CSF-mobilized PBSC (G-CSF/PBSC) could differentiate into a population of NK cells which were CD56+(bright)/CD3- and showed morphologic characteristics of large granular lymphocytes. Immunophenotypic analysis of the NK cells thus generated showed that a small proportion of them expressed CD2, CD8 and CD16 surface markers and approximately half of them coexpressed CD7. This NK population exhibited cytotoxic activity against a NK-sensitive cell line, K562. These observations suggest that CD34+ cells from G-CSF/PBSC contain precursors of NK cells that can differentiate into functional NK cells.
Adult↗
Serum level of interleukin-4 in patients with perennial allergic rhinitis during allergen-specific immunotherapy.
Interleukin-4 (IL-4) may play a central role in the IgE synthesis system, the development of Th-2-like cells, and co-ordination as well as the persistence of airway inflammatory process in allergic disorders. Therefore, IL-4 plays a key role in airway allergic disorders. This study aimed at investigating the serum concentrations of IL-4 in patients with perennial allergic rhinitis, with special reference to the possible changes and the clinical relevance following long-term immunotherapy. The study has demonstrated that the serum level of IL-4 in allergic rhinitis patients before immunotherapy is significantly higher than that in non-atopic individuals. However, the serum IL-4 level in allergic rhinitis patients did not decrease following anti-allergic medications but significantly decreased following immunotherapy. The percentage decrease in IL-4 was correlated significantly with the percentage decrease in specific IgE antibodies following long-term immunotherapy. Immunotherapy also significantly decreased specific IgE anti-bodies, but this reduction in specific IgE antibodies was not significantly correlated with the clinical improvement. In contrast, the percentage decrease in serum IL-4 was significantly correlated with the percentage decrease in symptomatic scores. The authors interpret these data to mean that immunotherapy alters T-cell cytokine profiles in the long-term, and a decline of IL-4 following immunotherapy could modulate not only production of specific IgE antibodies but also inflammatory cellular events, leading to symptomatic relief in allergic rhinitis.
Adolescent↗
G-CSF-induced mobilization of peripheral blood stem cells from healthy adults for allogeneic transplantation.
We investigated a dose-escalation effect of G-CSF (5, 10, and 15 micrograms/kg) on mobilization of committed and primitive hemopoietic progenitor cells, including CFU-GM, BFU-E, and long-term culture-initiating cells (LTC-IC) in addition to CD34+ cells and yields of progenitor cells in PBSC harvests obtained by leukapheresis of healthy adult donors. Results indicate that the mobilization of these progenitor cells is both dose and time dependent. Despite the very small number of healthy donors studied, it is estimated from our data that a sufficient number of CD34+ cells for allogeneic PBSC transplant (PBSCT) could be collected using a 5 day administration of 10 micrograms/kg of G-CSF to normal adult donors. Adverse effects include general fatigue and bone pain in most of the donors and fever and headache in some. These symptoms were well tolerated in most instances. Laboratory test abnormalities, including transient thrombocytopenia, increased platelet aggregation, and increased serum levels of some liver enzymes, were induced by G-CSF administration, but all were reversible within a short time. These observations suggest that hemopoietic stem cells for allogeneic PBSCT can be mobilized by short-term administration of a relatively high-dose G-CSF.
Adult↗
Genotypes of sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase II gene in substrains of spontaneously hypertensive rats.
OBJECTIVE: To search for a genetic marker of the sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase (SERCA) II gene in spontaneously hypertensive rats (SHRs) and to investigate differences in blood pressure and intracellular Ca2+ among some substrains of SHRs and Wistar-Kyoto (WKY) rats related to their SERCA II genotypes. DESIGN AND METHODS: The coding region of the SERCA II gene was sequenced in SHRs. Blood pressure and intracellular Ca2+ concentration ([Ca2+]i) in platelets were measured in substrains of SHRs and WKY rats with different SERCA II genotypes. RESULTS: A point mutation that provided restriction fragment length polymorphisms (RFLPs) by HindIII or Saul was found in the SERCA II gene. The polymerase chain reaction (PCR) products were digested by HindIII in SHR substrains and WKY-Kyoto rats, whereas they were digested by Saul in normotensive strains and SHR-Toho. Among SHR-Kyoto, SHR-Toho, WKY-Kyoto and WKY-Charles River, the substrains with the HindIII-digested SERCA II genotype showed slightly but significantly higher systolic blood pressure and augmented agonist-stimulated [Ca2+]i than those with the Saul-digested genotype. CONCLUSIONS: RFLPs were found in the SERCA II gene. In the substrain analysis of SHRs and WKY rats, higher blood pressure and increased [Ca2+]i were associated with the SERCA II genotype digested by HindIII. The SERCA II gene locus has the potential to contribute to the development of hypertension and abnormal intracellular Ca2+ metabolism in SHRs. These RFLPs in the SERCA II gene should be a useful genetic marker.
Animals↗
Indigenous bacterial flora of medicinal leeches and their susceptibilities to 15 antimicrobial agents.
Surface bacterial flora, as well as homogenates, of medical leeches, Hirudo medicinalis and Hirudinaria manillensis, were surveyed and the susceptibility of these isolates to 15 antimicrobial agents was examined. Aeromonas spp. were isolated from all leeches, and Pseudomonas fluorescens and other glucose-non-fermenting gram-negative rods (NF-GNR) were frequent isolates. Isolates were highly resistant to cephalosporins but susceptible to carbapenems, aminoglycosides and ofloxacin. The results indicate that prophylaxis with antimicrobial agents active against Aeromonas spp. and NF-GNR is necessary to avoid opportunist infections caused by indigenous leech flora during medical leech therapy on immunocompromised patients.
Aeromonas↗
Comparative study of fetal behaviour in a case of monozygotic twins, one being anencephalic.
Fetal behavior in monozygotic twins, one being anencephalic, was serially recorded from 20 to 35 weeks of gestation and analyzed. The commencement of breathing movement was concluded to reflect the development of the medulla oblongata of the fetus.
Adult↗
Evaluation of perospirone (SM-9018), a novel serotonin-2 and dopamine-2 receptor antagonist, and other antipsychotics in the conditioned fear stress-induced freezing behavior model in rats.
We studied the effects of perospirone (SM-9018), a novel serotonin-2 (5-HT2) and dopamine-2 (D2) receptor antagonist (SDA), on conditioned fear stress (CFS)-induced freezing behavior in rats and compared its actions with those of other antipsychotics. Exposure of rats to the environment previously paired with foot shock induced marked freezing behavior, which was reduced by the anxiolytic diazepam (0.1-3 mg/kg, p.o.) or antidepressants, desipramine and imipramine (10-100 mg/kg, p.o.). Perospirone at 0.3-3 mg/kg, p.o. significantly attenuated the CFS-induced freezing behavior in a dose-dependent manner, while the effect was reduced at the higher dose of 6 mg/kg. Other SDA-type antipsychotics, clozapine (1-30 mg/kg, p.o.) and risperidone (0.03-1 mg/kg, p.o.), and selective 5-HT2 antagonists, ritanserin (0.1-1 mg/kg, p.o.) and ketanserin (0.3-1 mg/kg, p.o.), all reduced the freezing behavior with U-shaped dose-response curves. However, neither conventional antipsychotic, haloperidol (0.1-3 mg/kg, p.o.), chlorpromazine (3-100 mg/kg, p.o.), thioridazine (3-100 mg/kg, p.o.), mosapramine (3-100 mg/kg, p.o.) nor tiapride (30-1000 mg/kg, p.o.) reduced the CFS-induced freezing behavior. In addition, subacute treatment of rats with perospirone (1-10 mg/kg/day) or imipramine (30 mg/kg/day) for 2 weeks prevented the induction of the freezing behavior by CFS. These findings suggest that SDA-type antipsychotics including perospirone are effective for the treatment of mood disturbances such as anxiety and depressive mood associated with schizophrenia and have a broader efficacy profile as compared with the conventional antipsychotics.
Animals↗
Unexplained increase in serum corticosteroid-binding globulin levels in a patient with chronic thyroiditis, pituitary adenoma and empty sella.
Unexplained high serum corticosteroid-binding globulin (CBG) concentrations (mean +/- SD, 74.1 +/- 12.1 micrograms/dl; normal women, 32.5 +/- 5.6 micrograms/dl) were found in an unmarried women who was not pregnant or taking exogenous estrogens. She was also found to suffer from subclinical chronic thyroiditis, pituitary adenoma and empty sella. The increased serum CBG concentrations in this patient were not due to any of the factors known to increase CBG. Consistently high basal serum GH levels and unusual GH responses to GH-releasing factor (GRF) and L-dopa were also noted.
Adenoma↗
The possibility of predicting tissue accumulation after repeated dosing using a single-dose tissue distribution study.
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Animals↗