[Monitoring of therapeutic courses of acute leukemia by application of mathematical models].
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Cell Cycle↗
Biomedical subjects
N Yamaguchi
Publications and source records attributed to N Yamaguchi.
[Megakaryocytic leukemia cell lines and megakaryocytic leukemia].
Using the megakaryocytic leukemia cell lines, K-562 and CMK established from a Down's patient with acute megakaryoblastic leukemia, we studied the changes of antigen expression, cytosolic Ca2+ mobilization, thromboxane (TX) A2 formation and gene expression during megakaryocyte differentiation. We found that thrombospondin synthesis and platelet factor (PF)-4 gene expression were specific for mature megakaryoblasts, whereas collagen unresponsiveness and prostaglandin E1-induced Ca2+ mobilization were noted in immature megakaryoblasts alone. This experiment shows that functional and genetic analysis are useful for characterizing the leukemic megakaryoblastic cells. We analyzed the clinical, hematologic and genetic features of 4 patients with M7, and acute megakaryoblastic transformation of CML, MDS and essential thrombocythemia. In two patients, prednisolone and 6-MP were effective in cytoreduction. In 3 patients with increased platelet counts, normal CFU-Meg formation, the megakaryoblasts with platelet production, or the coexistence of immature megakaryoblasts with mature megakaryocytes were observed, thus indicating that some megakaryoblastic leukemia cells still have the capacity of differentiation. One patient had megakaryoblastic cells with PF-4 gene expression. These clinical findings suggest that the megakaryoblastic leukemia could not be characterized as usual leukemia and a more sensitive marker is required to differentiate leukemic megakaryoblasts from normal megakaryoblasts.
Aged↗
[Morphometric study of the magnocellular basal forebrain system in patients with Alzheimer's disease].
Morphometric study of neurons within the magnocellular basal forebrain system (MBFS) in the three normal controls and three cases with Alzheimer's disease (AD) was studied. Immunocytochemical staining using anti-acetylcholinesterase was performed to identify the measuring areas of the MBFS, and cross sectional areas of all neurons within the MBFS in one preparation was measured making use of cresyl violet staining. About 50% of the entire neuronal cells within the MBFS were decreased and case 2 had neurofibrillary tangles in the substantia innominata. In the septal nucleus neuronal cell depopulation was observed through the all range of the neuronal cell size, and in the diagonal band of Broca neuronal cells of which cross sectional areas were more than 200 microns2 were preferentially decreased and case 3 had inverse increase of the neurons of which cross sectional areas were less than 200 microns2. In the basal nucleus of Meynert in the substantia innominata neurons of which cross sectional areas were more than 250 microns2 were markedly decreased and neurons of which cross sectional areas less than 250 microns2 were well preserved. The large neurons within the basal nucleus and diagonal band of Broca were more affected in AD. In the septal nucleus and diagonal band it was suspected that non-cholinergic neurons were also decreased and these findings suggested that other series of monoamines also bore a relationship to the dementia and neuropsychological symptoms in AD.
Acetylcholinesterase↗
Fluctuation of trypsin-like proteinase activity in the cell cycle of synchronized and growing HeLa cells, and the effect of GMCHA-OPhBut.
HeLa cells synchronized by double-thymidine block were grown in Eagle's minimum essential medium supplemented with 10% calf serum, and the fluctuation of trypsin-like protease activity in the cell cycle was examined. Seven distinct activity peaks were observed in one cell cycle at a cell density of 2%: two peaks in S phase, one peak at the S/G2 boundary, one peak in early M phase and one at the M/G1 boundary, and two peaks in G1 phase. HeLa cells synchronized by a mitotic detachment technique also showed similar results at cell density of 4.8%. The appearance of trypsin-like proteinase activity in the cell cycle was markedly affected by cell density, and no definite peak was observed above 8%. trans-Guanidinomethylcyclohexanecarboxylic and 4-tert-butylphenyl ester (GMCHA-OPhBut), a specific inhibitor for trypsin and a strong inhibitor of HeLa cell growth, had no effect on the various events in the first S, G2 and M phases, such as the incorporation of [methyl-3H]thymidine into DNA, the increase in the cell concentration, and the appearance of trypsin-like proteinase activity, whereas it retarded the onset of the second S phase and the various events in the second S, G2 and M phases for 3 h. In particular, it induced the appearance of a new proteinase peak at the G1/S boundary.
Cell Count↗
Transforming growth factor beta induces IgA production and acts additively with interleukin 5 for IgA production.
Effects of transforming growth factor beta (TGF-beta) on IgA production by LPS-stimulated B cells have been studied. TGF-beta itself could augment polyclonal IgA production in concomitant inhibition of polyclonal IgM and IgG1 production. Furthermore, TGF-beta and IL-5 additively augmented IgA production. TGF-beta exerted its activity early in the culture (by 2 d in a 5-d culture) and IL-5 was required late in the culture. Surface IgA- (sIgA-) B cells responded to TGF-beta for the development of IgA-secreting cells. By contrast, sIgA+ B cells, but not sIgA- B cells, responded to IL-5 for IgA production. These results suggest that TGF-beta has a differential role in the induction of IgA production from IL-5 on murine-activated B cells.
Animals↗
The cloning and sequencing of alpha 1(VIII) collagen cDNAs demonstrate that type VIII collagen is a short chain collagen and contains triple-helical and carboxyl-terminal non-triple-helical domains similar to those of type X collagen.
We have isolated two overlapping cDNA clones covering 2425 base pairs encoding a short type VIII collagen chain synthesized by rabbit corneal endothelial cells. The cDNAs encode an open reading frame of 744 amino acid residues containing a triple-helical domain of 454 residues flanked by 117- and 173-residue amino and carboxyl non-triple-helical domains (called NC2 and NC1, respectively). Based on the identity between the DNA-derived amino acid sequence and the amino acid sequence of a type VIII collagen CNBr peptide obtained from rabbit corneal Descemet's membrane, we conclude that the cDNAs code for a type VIII collagen chain. We give this chain the designation alpha 1(VIII). The alpha 1(VIII) triple-helical domain contains eight imperfections in the Gly-X-Y repeated structure with Gly-X instead of a full triplet. The length of the triple-helical domain and number and relative locations of these imperfections are remarkably similar to those of chicken alpha 1(X) collagen. The amino acid sequence of the carboxyl three-quarters of the NC1 domain has high sequence similarity to that of alpha 1(X) collagen. These data suggest that the triple-helix coding portions and carboxyl three-quarters of the NC1 domains of the alpha 1(VIII) and alpha 1(X) genes have a common evolutionary origin.
Amino Acid Sequence↗
Elevation of intracellular calcium ion by prostaglandin E1 and its inhibition by protein kinase C in a human megakaryocyte leukemia cell line.
In the present study, we examined the effect of prostaglandin E1 (PGE1) on Ca2+ mobilization in a human megakaryocyte (the progenitor of platelets) leukemia cell line, designated as CMK. PGE1 caused a rapid and dose-dependent increase in the intracellular free calcium level ([Ca2+]i) associated with the elevation of cyclic AMP. The PGE1-induced elevation of [Ca2+]i was decreased by the prior addition of ethylene glycol bis(2-aminoethylether)tetraacetic acid to the medium by approximately 25% of the control. This result indicates that the PGE1-induced elevation of [Ca2+]i is due to influx of Ca2+ from the external medium and to mobilization of Ca2+ from intracellular stores. Pretreatment of CMK cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), a stimulus for protein kinase C, further enhanced the PGE1-induced increase in the cellular cyclic AMP level. Inversely, pretreatment of CMK cells with TPA (10 nM), prior to the addition of PGE1, inhibited the PGE1-induced elevation of [Ca2+]i. Dibutyryl cyclic AMP and forskolin did not elevate [Ca2+]i or affect the PGE1-induced Ca2+ mobilization. The inhibitory action of TPA in the PGE1-induced elevation of [Ca2+]i was mimicked by other protein kinase C-activating agents, such as 1-oleoyl-2-acetylglycerol and N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide, and was selectively restored by protein kinase C inhibitors, such as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride. Thus, the inhibitory modulation of TPA on the PGE1-induced elevation of [Ca2+]i is mediated through protein kinase C activation. PGE1 had no inductional effect of megakaryocytic phenotypic changes in CMK cells. The biological role of PGE1, which increased [Ca2+]i and cyclic AMP levels in the CMK cells, remains to be determined.
Alprostadil↗
[Measurement of effective hepatic blood flow using 99mTc-PMT SPECT and single blood sampling].
Effective hepatic blood flow (EHBF) was measured from an uptake constant using single blood sampling and 99mTc-PMT hepatobiliary SPECT data. After intravenous injection of 3 mCi (111 MBq) of 99mTc-PMT, serial 1 min SPECT data were obtained for 7 minutes. A time activity curve (TAC) over the heart, that was normalized with the 5 minutes venous sample concentration (%/dose/ml), was used as a blood clearance curve (B(t]. And a TAC of the whole liver, that was normalized with the injected dose of 99mTc-PMT (%/dose), was used as a hepatogram (L(t]. An uptake constant representing EHBF, was estimated from the Rutland's method L. (t)/B(t) was plotted against integral of otB(t)dt/B(t), and the slope of the least square fitted straight line was determined as the uptake constant. In 16 cases, significant correlation was obtained between the 99mTc-PMT hepatic uptake at 5 minutes and the EHBF estimated from the blood clearance (r = 0.85, p less than 0.001). While there was a much better correlation between the EHBF from uptake constant and the EHBF from blood clearance (r = 0.95, p less than 0.001). In conclusion, this analysis for uptake constant of 99mTc-PMT SPECT data enables us to estimate EHBF with single venous sampling and in relatively short acquisition time. This method is thought to be very valuable in clinical practice.
Humans↗
An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters.
An autopsy case of familial juvenile Alzheimer's disease with extensive involvement of the subcortical gray and white matters is reported. A 33-year-old woman showed a progressive dementia and died of cardiac failure at the age of 45. Neurological examination disclosed choreatic movements, myoclonus, rigidity, and generalized convulsion. Gross inspection of the brain showed a diffuse cerebral atrophy and marked degenerations of both the subcortical gray and white matters. Microscopically, numerous and extensive argyrophilic changes such as senile plaques, neurofibrillary tangles, and granulovacuolar degenerations were observed in the brain. The present case was characterized by a severe neuronal loss in the basal ganglia, substantia nigra, dentate nucleus, and thalamus as well as a marked myelin loss and axonal damage in the cerebral white matter. This case suggested a combination of multisystemic degeneration and primary degeneration of the cerebral white matter. The pathological similarity of this case to Creutzfeldt-Jakob disease and Pick's disease is discussed.
Adult↗
Redistribution of haloperidol after electroshock: experimental evidence.
We have previously reported that plasma and red blood cell levels of haloperidol, a neuroleptic agent, significantly increased immediately after electroconvulsive shock therapy (ECT) in schizophrenic patients on long term haloperidol treatment. To elucidate the mechanism of this increase, we attempted to reproduce this phenomenon in female Wistar rats. After 4 successive days of ip administration of haloperidol (10 mg/kg body weight, once daily), rats were given ECT through corneal electrodes on the fifth day (a.c. 50 Herz, 55 mA, 2.0 sec). Haloperidol levels were determined in plasma and other major tissues using a radioreceptor assay for haloperidol distribution before and after ECT at appropriate time intervals. Plasma haloperidol level was significantly increased 1 min after ECT but tended to return to the control level (without ECT) after 5 min. A significant decrease in haloperidol concentration in tissues was not observed in any of the tissues examined including frontal cerebrum, striatum, and muscle tissues (gluteal muscles). However, the relatively high haloperidol level and the large volume of muscle tissues suggested that the muscle could be the source of the transient increase in haloperidol levels in plasma. This conclusion was also supported by the data showing no significant rise of plasma haloperidol level after ETC in rats previously given a muscle relaxant, succamethonium chloride.
Animals↗
Maternal antigenic stimulation actively produces suppressor activity in offspring.
Pregnant B10.A(3R) and B10.A(5R) mice were immunized with heterologous erythrocyte and protein antigens and the active immune responsiveness of their offspring was investigated by the plaque-forming cell (PFC) assay. In offspring derived from mothers which were stimulated with optimal amounts of antigens and which had fully developed antibody-forming cells, there was a clear-cut suppression in development of specific PFC over a significant period after delivery. In order to characterize the suppressor cell population, spleen cells were prepared from offspring whose mothers were immunized and thereafter treated by anti I-Jk or anti I-Jb monoclonal antibody and complement (C') followed by adoptive transfer to normal corresponding mouse strain. Only the group that received 3R spleen cells treated with anti I-Jb monoclonal antibody and C' had no suppressed PFC. To clarify the suppressor site in offspring, precursor B-cells of experimental offspring responded as hapten specific antibody forming cells by employing homologous hapten and heterologous carrier antigens. These results suggest mechanisms for suppression in offspring whose mothers were stimulated during pregnancy.
Animals↗
Characterization of high-affinity receptors for interleukin 5 on interleukin 5-dependent cell lines.
Interleukin 5 (IL-5) is a glycosylated polypeptide that acts as a key factor for B-cell growth and differentiation. We demonstrated previously that there are two classes (high and low affinity) of IL-5 receptors on murine chronic B-cell leukemic cells (BCL1-B20). Treatment of surface-bound radiolabeled IL-5 with bivalent crosslinkers identified a polypeptide of Mr 92,500. In this study, we analyzed characteristics of high-affinity IL-5 receptors on IL-5-dependent early B-cell lines (T-88 and T88-M), mouse myeloma cells (MOPC-104E), and BCL1-B20 cells. All cell lines had two classes of IL-5 binding sites, but T88-M cells bore the highest number of high-affinity receptors. The number of high-affinity IL-5 receptors on BCL1-B20 cells could be up-regulated 3-fold by lipopolysaccharide and down-regulated by IL-5. Disuccinimidyl tartarate crosslinking of 35S-labeled IL-5 to the receptors on the T88-M and lipopolysaccharide-stimulated BCL1-B20 cells revealed two major 35S-labeled components of Mr 92,500 and Mr 160,000, even when the binding of 35S-labeled IL-5 was carried out under high-affinity conditions (100 pM 35S-labeled IL-5). The Mr 92,500 component, but not the Mr 160,000 component, was detected in the lysates of MOPC-104E and T-88 cells, both of which bore a large number of low-affinity receptors and a limited number of high-affinity receptors. The results suggest that the Mr 92,500 component represents the complex of IL-5 with the low-affinity Mr 46,500 receptor, whereas the high-affinity receptor consists of the Mr 46,500 peptide and an additional peptide.
Adjuvants, Immunologic↗
Mechanisms of the interleukin 5-induced differentiation of B cells.
Interleukin 5 (IL5), a lymphokine produced by T cells, induces differentiation of B cell chronic leukemia BCL1-B20 cells into IgM-producing cells accompanied with growth arrest. To elucidate the intracellular mechanisms, the roles of Ca2+ mobilization and protein phosphorylation in the activation of the cells were examined. F(ab')2 fragment of anti-immunoglobulin (anti-Ig), which cross-links membrane-bound Ig, and calcium ionophore A23187 caused a rapid increase in the intracellular free calcium concentration [( Ca2+]i), whereas these stimulants did not give rise to differentiation of the cells. In contrast, treatment with IL5 did not affect either [Ca2+]i or the rates of Ca2+ uptake from the outside and release from the inside of the cells. Analysis by two-dimensional gel electrophoresis revealed that the in vitro phosphorylation of acidic 80-, 60-, and 45-kDa proteins was induced upon stimulation with IL5. Treatment with IL5 also caused a marked decrease in the in vitro phosphorylation of an acidic 100-kDa protein which was highly phosphorylated in the unstimulated state. Addition of phorbol 12-myristate 13-acetate (PMA) to the culture inhibited IL5-mediated differentiative responses. Therefore, these results suggest that Ca2+ mobilization is not involved but activities of stimulatory and inhibitory kinases may be involved in the IL5-mediated differentiation process.
Animals↗
Characterization of variant gamma-glutamyl transpeptidase produced by pancreatocholangiocarcinoma cell lines in a protein-free, chemically defined medium.
Four pancreatocholangiocarcinoma cell lines (HPC-Y1, HPC-YT, MIA PaCa-2, and HChol-Y1) were established to propagate in a protein-free, chemically defined medium. High gamma-glutamyl transpeptidase (GGTP) activities were showed in their spent media (designated as the secreted (GGTP). Their GGTP activities in the spent media were 125, 85, 110, and 153 IU/L/mg of lyophilized spent media, whereas GGTP activities extracted from their cancer cell lines with bromelain were 105, 37, 86, and 112 IU/L/1 x 10(6) cells, respectively. The chemical characteristics of the GGTPs in the spent media from these cell lines resembled one of the GGTPs, sialic acid-rich GGTP, extracted from normal human pancreas with bromelain treatment as follows: the GGTPs secreted from the cancer cell lines bound to an anion exchange column moved fast on electrophoresis and then showed decreased electrophoretic mobility with neuraminidase treatment, showed a high affinity for concanavalin A and lentil lectin columns, and had an acidic isoelectric point. However, the elution patterns of erythroagglutinating phytohemagglutinin (E-PHA) column chromatography and thermostability tests demonstrated clear differences between the carcinoma GGTPs both in the spent media and cell lines and the sialic acid-rich GGTP of normal pancreas, namely the carcinoma GGTPs treated with neuraminidase showed affinity to E-PHA columns, and, in addition, the GGTPs in the spent media showed an apparent heat resistance at 56 degrees C. These findings indicate that the carcinoma GGTPs have a different oligosaccharide structure from that in normal pancreatic GGTPs.
Adenoma, Bile Duct↗
Signal transduction through interleukin-5 receptors.
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Animals↗
Risk factors for leukemia occurrence among growth hormone users.
A matched case-control study on leukemia occurrence among growth hormone (GH) users was performed to elucidate any risk factor for leukemia. The total doses of GH and administration of other hormones, such as thyroxine, gonadotropin, gonadal hormones, glucocorticoid and anabolic steroid, did not lead to any apparent difference between cases studied and controls. Neither doses of diagnostic X-rays nor therapeutic cranial irradiation was related to leukemia risk. Scintigraphy for thyroid function using radioactive iodide was the only significant risk factor (P = 0.03). Hematological changes and liver function before and one month after GH administration were compared and the cases studied showed more proliferative reaction of white blood cells with rapid increase of neutrophils, but lymphocyte response was variable. Lactic acid dehydrogenase, alkaline phosphatase, glutamic oxalacetic transaminase, glutamic pyruvic transaminase tended to decrease after GH treatment when the patients had shown abnormally increased levels. Other environmental and familial factors did not show any abnormal clusters.
Adolescent↗
Evidence that increases in circulating catecholamines of adrenal origin are not involved in pressor response to bilateral carotid occlusion in anaesthetized dogs.
1. We studied whether or not circulating catecholamines of adrenal origin play a major role in cardiovascular responses evoked by bilateral carotid artery occlusion (3 min) in anaesthetized dogs. 2. In the control group, the following parameters increased significantly (P less than 0.05) during bilateral carotid occlusion: aortic systolic pressure, heart rate, net adrenal catecholamine output, net renal noradrenaline output, and plasma catecholamine concentrations in aortic blood. Similar responses were obtained during the second occlusion performed approximately 25 min after the first occlusion. 3. After functional adrenalectomy (ADRX: diversion of adrenal venous blood flow), the increase in aortic adrenaline concentration observed during bilateral carotid occlusion was abolished. The increase in aortic noradrenaline concentration during the occlusion was significantly attenuated by approximately 60% (P less than 0.01) after ADRX. 4. The increase in net renal noradrenaline output during bilateral carotid occlusion after ADRX was not different from that observed before ADRX. Similarly, the response of aortic systolic pressure and heart rate during the occlusion was unaffected by ADRX. Furthermore, the increase in net adrenal catecholamine output during the occlusion was not affected by ADRX itself. 5. From these results, we conclude that the increase in circulating catecholamines of adrenal origin during bilateral carotid occlusion is not a major determinant for the increases in aortic pressure and heart rate. The results suggest that these cardiovascular responses during the occlusion are mediated principally by neuronal noradrenaline released from peripheral sympathetic nerve terminals.
Adrenal Glands↗
Further postmortem examination of a case of familial ataxia with cerebrospinal fluid abnormality: an electron microscopic study of the intracytoplasmic eosinophilic inclusion bodies in the central nervous system.
As reported previously, the peculiar intracytoplasmic eosinophilic inclusion bodies (IEIBs) extensively appeared in the autopsied brain tissue from a 49-year-old man having familial ataxia with cerebrospinal fluid abnormality, and histochemically showed abundant proteins, but few lipids and carbohydrates. Ultrastructurally, many membrane-bound vacuoles derived from the distended cisterns of rough-surfaced endoplasmic reticulum (RER) appeared in the neurons. They were filled with fine granular, less dense materials. The IEIBs, shown as a homogeneous dense core, were found in some of the vacuoles. Similar vacuoles also appeared in astrocytes, oligodendrocytes, vascular pericytes, ependymal and choroidal epithelial cells. It is suggested that the vacuoles result from the accumulation of metabolic products in the distended RER cisterns of the cells in the central nervous system, presumably representing a genetically determined functional abnormality of the RER in protein synthesis and/or transport.
Astrocytes↗