[A case of Sweet syndrome with severe muscular pain].
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Biomedical subjects
Publications and source records attributed to S Asano.
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In 1983, a parvo-like virus (Yamanashi isolate) was newly isolated from silkworm. However, unlike parvovirus, two DNA molecules (VD1 and 2) were always extracted from purified virions. To investigate the structure and organization of the virus genomes, we determined the complete nucleotide sequence of VD2. The sequence consisted of 6031 nucleotides (nts) and contained a large open reading frame (ORF1) with 3513 nts. A smaller open reading frame (ORF2) with 702 nts was found in the complementary sequence. Computer analysis revealed that both ORFs did not code for the major structural proteins (VP1, 2, 3, and 4). These results suggest that VD2 has not enough information to produce progeny virions by itself. Further, the structural importance of the terminal sequence (CTS) common to both VD1 and VD2 was also predicted by a computer analysis.
Immunosuppressants cyclosporin A (CsA), FK506, and KM2210 modulated colony formations of murine hematopoietic progenitor cells. In a 4-h treatment with CsA, 10 micrograms/ml increased the formation of colony-forming units of mixed lineages (CFU-Mix) but decreased the formation of highly proliferative potential colony-forming units (CFU-HPP); 1 microgram/ml of CsA increased the formations of CFU-HPP, CFU-Mix, and colony-forming units of granulocytes/macrophages (CFU-GM); 0.1 microgram of CsA increased the formation of CFU-Mix and burst-forming units of erythroid lineage (BFU-E). Lower doses of CsA appeared to induce an increase in various colony formations. FK506 increased CFU-HPP and CFU-Mix formations at lower doses. Another immunosuppressant, KM2210, increased CFU-HPP and CFU-GM formations but decreased CFU-Mix and BFU-E formations. In a 24-h treatment, 10 micrograms/ml and 1 microgram/ml of CsA inhibited all the colony formations, but 0.1 microgram/ml of CsA increased CFU-Mix, CFU-GM, and BFU-E formations. Similarly, 100 ng/ml and 10 ng/ml of FK506 decreased all the colony formations but 1 ng/ml of FK506 increased CFU-HPP and CFU-GM formations. KM2210 inhibited all the colony formations. These findings showed that lower doses of CsA and FK506 appeared to increase the colony formations, although higher doses of these drugs decreased the colony formations, similar to the findings in a 4-h treatment. On the other hand, KM2210 showed opposing effects on colony formation with 4-h and 24-h treatments.
To clarify the clinicopathological significance of the suppurative lesions without an epithelioid granulomatous response (SLs without Ep) in lymph nodes and their relationship to abscess-forming granulomatous lymphadenitis (AGL) and cat scratch disease (CSD), 10 cases were assessed clinicopathologically and immunohistologically. SLs without Ep were located in the subcapsular sinus, paracortical area and medullary cords, but not in the germinal centers. The microabscesses were surrounded by collections of monocytoid B-lymphocytes (MBLs), histiocytes without epithelioid features, neutrophils, small lymphocytes and small numbers of plasma cells. The majority of the MBLs seen in the SLs without Ep were of the large cell type. The histological triad of toxoplasmic lymphadenitis, i.e., reactive follicular hyperplasia, small clusters of epithelioid cells and aggregates of MBLs, were also seen in all cases. Some of the clinical and pathological findings in our 10 cases were characteristic of CSD, i.e., (1) cat exposure before the lymphadenopathy was in four of the 10 cases, (2) occurrence in autumn and winter months in all cases, (3) typical suppurative granulomas surrounded by palisaded epithelioid cells were in four of the 10 cases, and (4) Warthin-Starry silver stain-positive bacteria were detected in seven of the 10 cases. The results of our study suggest that SLs without Ep are an early stage of CSD.
In summary, we have shown that adenovirus vector efficiently introduced foreign gene into cultured renal cells both of mesangial and tubular origin. Genes transferred were properly expressed to produce the molecules of expected function. It was possible to introduce the gene into nearly 100% of the cells treated. Expression of the gene began as early as 12 hours after the infection, increased until 48 hours and persisted at least up to eight days. Finally, the vector was non-toxic to the cells, as judged from simple toxicity tests. Successful application of adenovirus vector enables for us to study function of pertinent molecules in suitable host cells and opens a new way for examining renal cellular physiology and pathophysiology.
The effect of ascorbic acid on Ca2+ uptake in cultured rat astrocytes was examined in the presence of ouabain and monensin, which are considered to drive the Na(+)-Ca2+ exchanger in the reverse mode. Ascorbic acid at 0.1-1 mM inhibited Na(+)-dependent Ca2+ uptake significantly but not Na(+)-dependent glutamate uptake in the cells, although the inhibition required pretreatment for more than 30 min. The effect of ascorbic acid on the Ca2+ uptake was blocked by simultaneous addition of ascorbate oxidase (10 U/ml). Na(+)-dependent Ca2+ uptake was also inhibited by isoascorbate at 1 mM but not by ascorbate 2-sulfate, dehydroascorbate, and sulfhydryl-reducing reagents such as glutathione and 2-mercaptoethanol. The inhibitory effect of ascorbic acid was observed even in the presence of an inhibitor of lipid peroxidation, o-phenanthroline, or a radical scavenger, mannitol, and the degrading enzymes such as catalase and superoxide dismutase. On the other hand, the inhibitory effect was not observed under the Na(+)-free conditions that inhibited the uptake of ascorbic acid in astrocytes. When astrocytes were cultured for 2 weeks in a medium containing ascorbic acid, the content of ascorbic acid in the cells was increased and conversely Na(+)-dependent Ca2+ uptake was decreased. These results suggest that an increase in intracellular ascorbic acid results in a decrease of Na(+)-Ca2+ exchange activity in cultured astrocytes and the mechanism is not related to lipid peroxidation.
The effects of nitric oxide (NO)-generating agents on 45Ca2+ uptake in rat brain slices and cultured rat astrocytes were studied in the presence of monensin, which is considered to drive the Na(+)-Ca2+ exchanger in the reverse mode. Sodium nitroprusside (SNP) at > 10 microM increased monensin-stimulated Ca2+ uptake in the slices, although it did not affect high K(-)-stimulated Ca2+ uptake. Another NO donor, 3-morpholinosydnonimine, was effective. The effect of SNP was antagonized by hemoglobin (50 microM), a NO scavenger, and mimicked by 8-bromo-cyclic GMP (100 microM). In rat brain synaptosomes, SNP increased monensin-stimulated Ca2+ uptake, but it did not affect high K(+)-stimulated Ca2+ uptake. 8-Bromocyclic GMP, but not SNP, increased Na(+)-dependent Ca2+ uptake significantly in synaptic membrane vesicles in the absence of monensin. In cultured rat astrocytes, SNP and 8-bromo-cyclic GMP increased Ca2+ uptake in the presence of ouabain and monensin, which were required for the Ca2+ uptake in the cells. These findings suggest that NO stimulates the Na(+)-Ca2+ exchanger in neuronal preparations and astrocytes in a cyclic GMP-dependent mechanism.
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1. 5-Hydroxytryptamine (5-HT) plays a role in the regulation of noradrenergic neurones in the brain, but the precise mechanism of regulation of noradrenaline (NA) release by 5-HT1A receptors has not been defined. The present study describes the effect of a highly potent and selective 5-HT1A receptor agonist, 5-(3-[[(2S)-1,4-benzodioxan-2-ylmethyl)]amino]propoxy)-1,3-b enzodioxole HC1 (MKC-242), on NA release in the hypothalamus using microdialysis in the freely moving rat. 2. Subcutaneous injection of MKC-242 (0.5 mg kg-1) increased extracellular levels of NA and its metabolite, 3-methoxy-4-hydroxyphenylglycol, in the hypothalamus and hippocampus. 3. The 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.2 mg kg-1) and buspirone (3 mg kg-1) mimicked the effect of MKC-242 in increasing NA release in the hypothalamus. 4. The effects of MKC-242 and 8-OH-DPAT in the hypothalamus were antagonized by pretreatment with WAY100135 (10 mg kg-1), a silent 5-HT1A receptor antagonist. 5. Local administration of 8-OH-DPAT (10-100 microM), citalopram (1 microM), a 5-HT reuptake inhibitor, and MDL72222 (10 microM), a 5-HT3 receptor antagonist, into the hypothalamus, had no effect on NA release. 6. Intracerebroventricular injection with 5,7-dihydroxytryptamine caused a marked reduction in brain 5-HT content, but the treatment affected neither basal NA levels nor the MKC-242-induced increase in NA release. 7. The effect of MKC-242 in increasing NA release was not attenuated by repeated treatment with the drug (0.5 mg kg-1, once a day for 2 weeks). 8. The present results suggest that activation of postsynaptic 5-HT1A receptors increases NA release in the hypothalamus.
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A human native immunoglobulin liquid preparation for intravenous injection, was used in combination with antibiotics and G-CSF to study its efficacy and safety in 49 patients with severe infections (Granulocyte counts were or= 38 degrees C) which had not responded to antibiotic and G-CSF therapy of a 3-day or more duration. As a result of the Committee judgment, 49 patients were included in this study; 30 (61.7%) were included in efficacy and safety analysis. The analysis of 30 patients consisted of 9 patients (30.0%) with suspected septicemia, 5 (16.7%) with pneumonia, and 4 (13.3%) with septicemia. All patients had severe underlying diseases such as leukemia and malignant lymphoma. Clinical efficacy of Immunoglobulin preparation was judged by the doctors in charge to be "excellent" and "good" in 70.0% of the total cases. The rate of effectiveness was calculated from the results of the Committee judgment was 83.3% when "excellent" and "good" cases were included. No side effects were observed in all cases. Our results suggest that the immunoglobulin in combination with G-CSF is very effective on patients with severe infections.
In order to examine the efficacy of the combination chemotherapy with miconazole and G-CSF, patients with deep mycosis and suspected deep mycosis were divided into 3 groups. Group I: miconazole and G-CSF were administered simultaneously. Group II: miconazole was administered later during G-CSF administration. Group III: only miconazole was administered. Of a total of 117 cases 105 cases were analyzed including group I 37 cases, group II 39 cases and group III 29 cases, excluding 12 dropout and inadequate cases. Of the 105 cases, deep mycosis were 31 and suspected deep mycosis were 74, and underlying diseases were hematological malignancies such as leukemias. Efficacy judged mainly by the change of fever was 62.2% (23/37) in group I, 43.6% (17/39) in group II, and 41.4% (12/29) in group III, respectively. Efficacy was better in the patients whose neutrophil counts increased from less than 500/microliters to more than 500/microliters (group I 75.0%, group II 72.7%) than in the patients whose neutrophil counts were less than 500/microliters throughout the time of miconazole administration (group I 33.3%, group II 33.3%). Adverse effects were minimal in 3 groups (group I 15.4%, group II 17.4%, group III 15.6%). It is concluded that the combination with miconazole and G-CSF is effective in the treatment of deep fungal infections.
The present study was undertaken to determine the localization of cells laden with secretory leukoprotease inhibitor (SLPI) in bronchial/bronchiolar epithelium (B/Br-E) by histochemical techniques to see whether SLPI production occurs in conjunction with pathologic bronchopneumonia. Ten lung were obtained at autopsy from patients between 63 and 100 yr of age, including six with pathologic pneumonia and four without pneumonia. SLPI-laden cells in the B/Br-E corresponded mostly to goblet cells with apparent hyperplasia. A morphometric study performed on the B/Br-E indicated that the percentage of SLPI-laden cells was significantly correlated with the percentage of mucus-containing cells (r = 0.72, p < 0.001). This trend was similar in the bronchi (r = 0.60, p < 0.05) and in the bronchioles (r = 0.90, p < 0.01). The increased percentage of mucus and SLPI-laden cells in the B/Br-E was closely correlated with acute inflammatory changes in the adjacent alveoli, particularly in bronchi rather than in bronchioles. From these observations we conclude that the number of SLPI-laden cells in the airways increases in correlation with goblet cell hyperplasia. In addition, these morphologic changes are associated with the existence of acute inflammatory cell infiltration in the alveolar area.
Earlier in vivo experiments suggest that serotonin1A (5-HT1A) agonists are new tools for the treatment of experimental cerebral ischemia. The present study examined this idea in an in vitro system. Incubation of rat brain slices under anoxic conditions for 30 min decreased protein synthesis that was assayed in a normoxic medium by measuring the incorporation of [14C]lysine into trichloroacetic acid-insoluble tissue extracts. The 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino) tetralin (10-100 microM) and buspirone (50 microM) attenuated the anoxia-induced decrease in protein synthesis in the slices. Although the degree of the effect is small, it may be relevant to the neuroprotective effect in the in vivo experiments.
The present study characterizes the neurochemical profile of the newly synthesized compound 5-(3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy)-1,3-be nzodioxole HCl (MKC-242). In in vitro experiments, MKC-242 had high affinity for serotonin1A (5-HT1A) receptors (Ki: 0.35 nM) and moderate affinity for alpha 1-adrenoceptors (Ki: 21 nM), whereas it had no appreciable affinity for any other neurotransmitter recognition sites studied and 5-HT transporter. MKC-242 (0.3-3.0 mg/kg, s.c.; 1-10 mg/kg, p.o.) caused presynaptic 5-HT1A-receptor-mediated responses (decreases in 5-HT turnover and 5-HT release) and postsynaptic 5-HT1A-receptor-mediated responses (hypothermia, an increase in serum corticosterone level and 5-HT1A behavioral syndrome). The effects of MKC-242 on decarboxylase inhibitor-induced 5-hydroxytryptophan accumulation and rectal temperature were blocked by the 5-HT1A-receptor antagonist N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropana mide. The comparative studies on the in vivo responses induced by MKC-242 and the 5-HT1A-receptor full agonist 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) showed that MKC-242 and 8-OH-DPAT had similar efficacy at presynaptic 5-HT1A receptors, whereas the former had less efficacy than the latter at postsynaptic 5-HT1A receptors. Furthermore, MKC-242 partially inhibited forskolin-stimulated adenylate cyclase activity in hippocampal membranes. These findings suggest that MKC-242 acts as a full and partial agonist at pre- and postsynaptic 5-HT1A receptors, respectively, in the central nervous system.
We serially measured the serum levels of soluble interleukin-2 receptor (sIL-2R) and soluble CD8 (sCD8) in 36 patients with malignant lymphoma (33 non-Hodgkin's lymphoma cases and three Hodgkin's disease cases). The level of serum sIL-2R was significantly elevated in patients with active disease (18) compared to those in remission (18), and correlated with the clinical stage of the lymphoma. The temporal profile of the sIL-2R level reliably represented the disease status, which was judged clinically, during the course of the disease. In three patients, the tumor bulk paralleled the sIL-2R level. On the other hand, a less significant correlation was found between the serum sCD8 level and disease activity. The serial measurement of sCD8 appeared to be less useful for monitoring the disease activity, although there was a significant correlation between the sCD8 and sIL-2R levels. This study indicates that serial measurement of the serum sIL-2R level may be useful for monitoring the tumor burden in response to treatment and for early detection of disease progression in malignant lymphoma.
The human tri-thorax gene (HRX) also called ALL-1 (Acute Lymphocytic Leukemia-1) as well as MLL (Myeloid-lymphoid or Mixed-lineage Leukemia) gene, is disrupted in the majority of leukemias with chromosomal abnormalities involving 11q23. The alteration of the gene is related to leukemogenesis of various types such as acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and acute mixed lineage leukemia. The gene is also rearranged in cases of secondary AML developing after exposure to chemotherapeutic agents, especially topoisomerase II inhibitors. In at least one report, genomic analysis of this recombination site showed the breakpoint to be a topoisomerase II binding site and that exposure to the inhibitor could induce the rearrangement. If exposure induces the rearrangement of the gene, secondary ALL as well as secondary AML could occur after exposure to these agents, because the type of leukemias with rearranged HRX gene is not limited to AML. We present here such a case of secondary ALL with this gene rearrangement which occurred during adjuvant chemotherapy for breast cancer. Although less cases of secondary ALL are reported in comparison with those of secondary AML, such case reports have been accumulating. The incidence of this type of leukemia should be clarified in the future.