Brief report: severe symptoms of hyperhistaminemia after the treatment of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid)
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Biomedical subjects
Publications and source records attributed to A Aoki.
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The myoendocrine cells of the heart of Hypostomus cordovae (Günther 1880), a teleost fish from South America, were investigated by electron microscopy and immunohistochemistry. By applying antibodies raised against synthetic cardiodilatin 99-126 (CDD/ANP 99-126), a specific labeling of this hormone was found in the heart of this fish, mainly in myoendocrine cells of atrial trabeculae, where specific secretory granules are stored. The distribution of secretory granules exhibited striking seasonal variations. In winter there were fewer differentiated myoendocrine cells, which were easily recognized by the presence of specific secretory granules, most of which occur clustered in perinuclear areas of the cells. By contrast, in summer the majority of the myocardic cells of the atrium are active endocrine cells. They contain abundant secretory granules widely scattered in the cytoplasm, many of them polarized toward the subendocardial aspect of the cell. The secretory granules can be easily differentiated from the Weibel-Palade granules of endothelial cells, the shape, size and content of which were typical at electron-microscopic level. In addition, these endothelial granules did not display CDD immunoreactivity. The presence of cardiodilatin in a fish such as Hypostomus cordovae further supports the view that cardiac hormones are present in many Vertebrates and may preserve analogous roles such as those reported in other species throughout the group.
1. In this report the postnatal differentiation of the hypothalamic ventromedial nucleus (VMN) was studied. The main maturational changes detected at the fine structural level occurred between 10 and 20 days of postnatal life. 2. In 5-day-old rats the majority of neurons was undifferentiated, with rudimentary cytoplasmic organelles. Dendritic profiles presented an empty appearance due to an electron-lucent matrix and scarce content of organelles. 3. At 10 days there was a significant proliferation of cytoplasmic organelles in the perikaryon, mainly of those involved in protein biosynthesis as the rough endoplasmic reticulum (RER) and the Golgi complex. 4. After 20 days of age the VMN neurons acquired the cytological appearance of adult neurons, with well-organized RER, Golgi complexes, and pleomorphic mitochondria. Concurrent with these changes, there was a marked development of other organelles in the neuropil, which was accompanied by an increase in synaptic density and differentiation of their subsynaptic structures.
A graft-versus-host reaction (GVHR) was induced in (B10 x DBA/2)F1 (BDF1) and (BALB/c x A)F1 (CAF1) murine recipients by injection of their parental or B10.D2-derived spleen cells. The incidences of glomerulonephritis and autoantibody production were then correlated. All of the BDF1 mice that received DBA/2 spleen cells (termed DBA/2----BDF1) and 33% of the CAF1 mice that received BALB/c spleen cells (BALB/c----CAF1) developed glomerulonephritis. However, in other combinations (B10.D2----BDF1, A/J----CAF1) no significant glomerular lesions were observed. An analysis of antibodies by ELISA revealed that the groups with renal disease showed a significant polyclonal elevation of IgG class antibodies, including autoantibodies (anti-DNA, anti-MRBC, and NTA) and a conventional antibody (anti-TNP-KLH). No significant IgG class antibody production was observed in the groups that did not develop glomerulonephritis. Thus, it was suggested that an IgM to IgG class switch is important in the development of glomerulonephritis in GVHR. Other factors also appear to be involved. Only 33% of BALB/c----CAF1 developed glomerulonephritis, even though a level of IgG class antibody production was comparable to that observed in DBA/2----BDF1 in which 100% showed severe glomerulonephritis.
Our previous study demonstrated the positive relationship between the gene introduction rate into hematopoietic cell lines by electroporation and the percentage of cells in S-phase. In the present study, granulocyte-macrophage progenitor cells (CFU-C) rich marrow cell fraction were cultured in suspension with IL-3, GM-CSF and G-CSF for 4 days. The number of CFU-C were increased three times after the culture, and 3H-thymidine suicide tests of cultured cells demonstrated that the proportion of CFU-C in S-phase was increased by two to four times. The efficiency of gene transfer into CFU-C with the plasmid pMoZtk (containing the beta-galactosidase gene) by electroporation was nearly doubled by culturing marrow cells with these growth factors. These findings confirm that the introduction rate of the gene into CFU-C by electroporation is more efficient in cell populations with a higher percentage of CFU-C in S-phase.
Severe glomerulonephritis was induced successfully in (B10 x DBA/2)F1 (BDF1) mice by injection of parental DBA/2 lymphoid cells. The mice manifested typical nephrotic syndrome dying around 10 weeks post injection. Electron microscopical examination demonstrated electron dense deposits first in the mesangial matrix, then in the subepithelium compatible with immune complex glomerulonephritis. Subendothelial deposits were not observed. Immunofluorescent study revealed IgG deposition in the capillary wall and IgM in the mesangium early in the process. As the lesion progressed, both IgG and IgM were present in the mesangial area and along the capillary wall. Some glomeruli showed segmental mesangiolysis, suggesting that altered mesangial cells have a role in the development of glomerular change, which together with rise in serum anti-DNA antibody titer suggest that autoantibodies promote the glomerular lesions in this model system.
The glucocorticoid receptor is a member of the steroid and thyroid hormone receptor superfamily and acts as a ligand-activated transcription factor. To reconstitute the molecular mechanisms underlying the cellular response to soluble receptor ligands, we have exploited a cell-free system that exhibits glucocorticoid-induced activation of the latent cytosolic glucocorticoid receptor to an active DNA-binding species. We demonstrate here that cytosol from a rat hepatoma cell, M1.19, contains glucocorticoid receptor-specific immunoreactivities and target DNA-binding activities. Moreover, specific DNA-binding activities of M1.19 cytosol were dose-dependently induced by dexamethasone treatment, and linearly correlated with the hormonal induction of chloramphenicol acetyltransferase activity at the corresponding concentrations. These results indicate that the cytosolic glucocorticoid receptor could be converted in a DNA-binding form under cell-free conditions and the ligand appears to play a crucial role in the direct control of the level of functional activity of a given ligand-receptor complex.
The relationships between the stimulation of prolactin secretion and proliferation of lactotrophs was studied from a multidisciplinary standpoint in three experimental models. Administration of both oestrogen and sulpiride resulted in a significant increase in prolactin secretion and in the lactotroph population. A single injection of 10 micrograms oestradiol benzoate (OB) induced a twofold increase in the proliferation of lactotrophs (morphometrically as volume density), which increased further (2.5-fold) after three OB injections. Parallel changes were observed in the net counts made on lactotrophs sectioned through the nucleus to avoid possible distortions in volume density caused by hypertrophic cytoplasms. Comparable results were obtained with the mitotic index in the same groups of rats exposed to treatment with colchicine. The effect of sulpiride on proliferation of lactotrophs was also significant (1.7-fold) but less pronounced than in rats treated with oestrogens. The treatments with oestrogen and sulpiride did not stimulate lactotrophic activity in a similar way, as judged by the levels of serum prolactin and the storage patterns of small and big prolactin in pituitary glands. Serum prolactin (mean +/- S.E.M.) in control ovariectomized rats was 4.0 +/- 0.9 micrograms/l and one and three injections of OB raised these levels to 14.4 +/- 5.0 and 28.8 +/- 4.6 micrograms/l respectively. The highest levels of serum prolactin were seen in sulpiride-treated rats (467.2 +/- 28.7 micrograms/l). Striking differences occurred in the pituitary contents of big prolactin, the control values increasing from 5.3 +/- 0.5 to 10.2 +/- 1.3 micrograms/mg after one OB injection and to 14.7 +/- 0.7 micrograms/mg after three OB injections.(ABSTRACT TRUNCATED AT 250 WORDS)
A microwell cluster was manufactured with silicone rubber for incubating thin sections for postembedding electron microscopic immunocytochemistry. The small size of the wells requires only minute amounts (as little as 5 microliters) of antisera and other valuable immunoreagents. The capillary action of the wells holds the incubation media and grids in place, even if the cluster is turned upside down, thus facilitating safe transport and storage of the sections to be stained. This silicone rubber microwell cluster can also be used as a die to imprint wells in Parafilm sheets to be used for the same purpose.
The differentiation of endocrine myocardiocytes was investigated in the heart of developing toad Bufo arenarum Hensel, combining ultrastructural and immunocytochemical procedures. The distribution of immuno-reactive atrial natriuretic peptide (ANP) in the whole heart was appraised by light microscopy, applying biotin-streptavidin and immunofluorescence techniques. With the latter procedures ANP was first recognized at embryonic stage 22, in both atrium and ventricle. In the ensuing stages the ANP-reactivity became stronger in the atrium, while it became dimmer in the ventricle. At the end of the larval prometamorphic stage, atrial myocardiocytes acquired almost all the features of adult myoendocrine cells. At electron microscope level, small inclusions, about 110-120 nm in diameter, resembling secretory granules were found in myoendocrine cells beginning at embryonic stage 22. However, no immunogold labeling of ANP occurred until stage 25. The number of secretory granules diminished in the ventricles and increased in the atrium of the larval heart and at the end of the prometamorphic stage the atrial myoendocrine cells presented the ultrastructural characteristics of active secretory cells. The synthesis of ANP in larvae is enhanced at a critical period of development when the developing toad switches from an aquatic environment to terrestrial life. The cardiac hormones seem to play a key role in the regulation of the osmolarity of body fluids at this developmental stage.
Effects of recombinant human erythropoietin (rhEpo) and the combination of recombinant human interleukin-3 (rhIL-3) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) with rhEpo on erythroid colony formation were examined in vitro in 13 patients with aplastic anemia and 16 with myelodysplastic syndromes (MDS). The methylcellulose cultures of marrow cells from normals and the patients yielded no erythroid colonies in the absence of rhEpo. In normals, CFU-E and BFU-E colony formation was significantly increased by adding either rhIL-3 or rhGM-CSF with rhEpo, compared with rhEpo alone, and rhIL-3 was more potent than rhGM-CSF to form colony-forming units and burst-forming units of erythroid (CFU-E) (BFU-E) colonies. By adding rhIL-3 with rhEpo, CFU-E colony formation was increased in half of patients with RA, compared with rhEpo alone, and by rhGM-CSF, in one third. Approximately one third or one fourth of the patients with MDS showed increased BFU-E colonies when rhIL-3 or rhGM-CSF were added to rhEpo. Cultures containing rhIL-3 or rhGM-CSF with rhEpo yielded larger numbers of BFU-E colonies in half of the patients with nonsevere aplastic anemia than those containing rhEpo alone. These observations suggest that the combination of these growth factors, especially rhIL-3 with rhEpo, is applicable to the treatment of anemia in some patients with aplastic anemia and MDS.
The management of late metastases from renal cell carcinoma is often difficult because of multiple organ involvement. We report a case of multiple metastases from renal cell carcinoma in the duodenum, pancreas, intestine, falciform ligament and liver, 18 years after nephrectomy. The patient underwent a total pancreatectomy following a gastroduodenal arterial embolization to control duodenal bleeding, a resection of the ileum and falciform ligament at a second laparotomy and repeated hepatic arterial embolizations to control the growth of liver metastases. Aggressive treatment should be undertaken in cases of late recurrence of renal cell carcinoma after nephrectomy because of the possibly slow-growing biological character of the tumor.
A 57-year-old woman visited to our hospital complaining of paresthesia in the right leg. She had no abnormal physical findings. However, the peripheral blood examination demonstrated 7% basophilia with 8000/microliters WBC count and decreased neutrophil alkaline phosphatase activity (score 37, rate 19%). She was diagnosed as Ph1 chromosome positive CML in early phase by the chromosomal analysis of bone marrow cells. She received subcutaneous injection of natural interferon-alpha at a dosage of 600 x 10(4) IU daily from March 10, 1987. The dosage and administration interval were gradually reduced and prolonged. Since November 1988, weekly injections of 300 x 10(4) IU has been administered as maintenance therapy. Cytogenetic improvement was seen at 4 months after the start of IFN. Disappearance of Ph1 chromosome positive cells was observed on December 11, 1987. It was suggested that the administration of IFN from the early chronic phase played an important role in the control of the disease.
The distribution of lanthanum chloride and horseradish peroxidase within the full-term chorioallantoic placenta of the rat was investigated 1 to 20 min after administration of these tracers into the maternal blood circulation. Both tracers rapidly penetrate trophoblastic layer I and diffuse into the interspace between layers I and II. They are localized in extensive infoldings and caveolae of the outer surface of layer II. The syncytial character of layer II is confirmed at this development stage of the placenta. There is no vesicular uptake or penetration beyond layer II until 20 min after tracer administration. Our results indicate that trophoblastic layer II is the main barrier in the chorioallantoic rat placenta preventing the permeation of macromolecules from maternal to fetal compartments. With freeze-fracturing, particulate strutures of variable arrangement and size are found between adjacent cells of layer I. With goniometric analysis small gaps between the appositions of the membrane are observed. These structures are interpreted as tight and/or gap junctions during stages of assembly or disassembly.
The distribution of horseradish peroxidase and lanthanum chloride within the full term chorioallantoic placenta of the rat was examined after administration of these tracers into the umbilical artery. Both tracers rapidly traverse the capillary endothelium. Transendothelial channels, fenestrations and micropinocytotic vesicles provide the main pathways. Intercellular clefts which are either patent or interrupted by leaky intercellular junctions, also contribute to a rapid passage of low and high molecular weight substances. Deep channel-like invaginations, effecting an increase of the exchange area of layer III, are freely accessible to the tracers from the interspace between the capillary endothelium and trophoblastic layer III. The invaginations, however, are not in continuity with the interspace between layers II and III, verifying the syncytial character of layer III. Neither an uptake of the tracers nor a passage across layer III is observed. The main permeability barrier to feto-maternal transfer within the chorioallantoic placenta is localized in the syncytiotrophoblastic layer III. This layer controls the passage of low molecular weight substances and restricts the penetration of high molecular weight substances.
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