Biomedical subjects

Akira Shimizu

Publications and source records attributed to Akira Shimizu.

At least 19 recordsLinked to original sources

PubMed2006

Thymic rejuvenation and the induction of tolerance by adult thymic grafts.

The thymus, the site of origin of T cell immunity, shapes the repertoire of T cell reactivity through positive selection of developing T cells and prevents autoimmunity through negative selection of autoreactive T cells. Previous studies have demonstrated an important role for the thymus not only in central deletional tolerance, but also in the induction of peripheral tolerance by vascularized renal allografts in juvenile miniature swine recipients. The same protocol did not induce tolerance in thymectomized recipients nor in recipients beyond the age of thymic involution. We subsequently reported that vascularized thymic lobe grafts from juvenile donors were capable of inducing tolerance in thymectomized juvenile hosts. However, the important question remained whether aged, involuted thymus could also induce tolerance if transplanted into thymectomized hosts, which, if true, would imply that thymic involution is not an intrinsic property of thymic tissue but is rather determined by host factors extrinsic to the thymus. We report here that aged, involuted thymus transplanted as a vascularized graft into juvenile recipients leads to rejuvenation of both thymic structure and function, suggesting that factors extrinsic to the thymus are capable of restoring juvenile thymic function to aged recipients. We show furthermore that rejuvenated aged thymus has the ability to induce transplant tolerance across class I MHC barriers. These findings indicate that it may be possible to manipulate thymic function in adults to induce transplantation tolerance after the age of thymic involution.

Aging↗

PubMed2006

Spontaneous large-scale lymphoid neogenesis and balanced autoimmunity versus tolerance in the stomach of H+/K+-ATPase-reactive TCR transgenic mouse.

Autoimmunity is often accompanied by the development of ectopic lymphoid tissues in the target organ, and these tissues have been believed to have close relevance to the severity of the disease. However, the true relationship between the extent of such lymphoid structures and the intensity or type of immune responses mediated by self-reactive T cells has remained unclear. In the present study, we generated transgenic mice expressing TCR from an autoimmune gastritis (AIG)-inducing Th1 cell clone specific for one of the major stomach self-Ags, H(+)/K(+)-ATPase alpha subunit. The transgenic mice spontaneously develop massive lymphoid neogenesis with a highly organized tissue structure in the gastric mucosa, demonstrating Ag-specific, T cell-mediated induction of the lymphoid tissues. Nevertheless, the damage of surrounding tissue and autoantibody production were considerably limited compared with those in typical AIG induced by neonatal thymectomy. Such a moderate pathology is likely due to the locally restricted activation and Th2 skewing of self-reactive T cells, as well as the accumulation of naturally occurring regulatory T cells in the target organ. Altogether, the findings suggest that lymphoid neogenesis in chronic autoimmunity does not simply correlate with the destructive response; rather, the overall activation status of the T cell network, i.e., the balance of self-reactivity and tolerance, in the local environment has an impact.

Adoptive Transfer↗

PubMed2006

Knock-down of 25 kDa subunit of cleavage factor Im in Hela cells alters alternative polyadenylation within 3'-UTRs.

Alternative polyadenylation leads to mRNAs with variable 3' ends. Since a 3'-untranslated region (3'-UTR) often contains cis elements that impact stability or localization of mRNA or translation, selection of poly(A) sites in a 3'-UTR is regulated in mammalian cells. However, the molecular basis for alternative poly(A) site selection within a 3'-UTR has been unclear. Here we show involvement of cleavage factor Im (CFIm) in poly(A) site selection within a 3'-UTR. CFIm is a heterodimeric 3' end-processing complex, which functions to assemble other processing factors on pre-mRNA in vitro. We knocked down 25 kDa subunit of CFIm (CFIm25) in HeLa cells and analyzed alternative poly(A) site selection of TIMP-2, syndecan2, ERCC6 and DHFR genes by northern blotting. We observed changes in the distribution of mRNAs in CFIm25 depleted cells, suggesting a role for CFIm in alternative poly(A) site selection. Furthermore, tissue specific analysis demonstrated that the CFIm25 gene gave rise to 1.1, 2.0 and 4.6 kb mRNAs. The 4.6 kb mRNA was ubiquitously expressed, while the 1.1 and 2.0 kb mRNAs were expressed in a tissue specific manner. We found three likely poly(A) sites in the CFIm25 3'-UTR, suggesting alternative polyadenylation. Our results indicate that alternative poly(A) site selection is a well-regulated process in vivo.

3' Untranslated Regions↗

PubMed2006

Proteomics-based approach identifying autoantibody against peroxiredoxin VI as a novel serum marker in esophageal squamous cell carcinoma.

PURPOSE: Detection of novel tumor-related antigens and autoantibodies will aid in diagnosis of early-stage cancer and in development of more effective immunotherapies. The purpose of this study was to identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC) cell line (TE-2) and related autoantibodies in sera from patients with ESCC using a proteomics-based approach. EXPERIMENTAL DESIGN: TE-2 proteins were separated by two-dimensional PAGE, followed by Western blot analysis in which sera of patients with ESCC, healthy controls, and patients with other cancers were tested for primary antibodies. Positive spots were excised from silver-stained gels and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS). RESULTS: Sera from patients with ESCC yielded multiple spots, one of which was identified as peroxiredoxin (Prx) VI by MALDI-TOF/TOF MS. Western blot analysis against recombinant Prx VI showed reactivity in sera from 15 of 30 (50%) patients with ESCC and 2 of 30 (6.6%) healthy individuals. Autoantibody against Prx VI was found in sera from 1 of 30 (3.3%) patients with other types of cancer (colon cancer). CONCLUSION: We have identified for the first time an autoantibody against Prx VI in ESCC patients. The proteomic approach implemented here offers a powerful tool for identifying novel serum markers that may display clinical usefulness against cancer.

Adult↗

PubMed2006

Diffusion dynamics of the li atom on amorphous carbon: A direct molecular orbital-molecular dynamics study.

Direct molecular orbital-molecular dynamics (MO-MD) calculation was applied to diffusion processes of the Li atom on a model surface of amorphous carbon and compared with the diffusion mechanism of Li+ ion. A carbon sheet composed of C96H24 was used as the model surface. The total energy and energy gradient on the full dimensional potential energy surface of the LiC96H24 system were calculated at each time step in the trajectory calculation. The optimized structure, where the Li atom is located at the center of mass of the model surface, was used as the initial structure at time zero. Simulation temperatures were chosen in the range of 200-1250 K. The dynamics calculations showed that the Li atom vibrates around the initial position below 250 K, and it moves above 300 K. At middle temperature, the Li atom translates freely on the surface. At higher temperature (1000 K), the Li atom moves from the center to edge region of the model surface and is trapped in the edge. The activation energy calculated for the Li atom is larger than that for the Li+ ion. This difference is due to the fact that the Li atom diffuses together with an unpaired electron on the carbon surface. The diffusion mechanism of the Li atom was discussed on the basis of the theoretical results.

Journal Article↗

PubMed2006

Odor-driven activity in the olfactory cortex of an in vitro isolated guinea pig whole brain with olfactory epithelium.

We developed a new technique to isolate a whole guinea pig brain with an intact olfactory epithelium (OE) that enables us to access the ventral surface of the brain including olfactory areas with ease during natural odor stimulation. We applied odorants to OE and confirmed that odor-induced local field potentials (LFPs) could be induced in olfactory areas. In the olfactory bulb (OB) and the piriform cortex (PC), odor-induced LFPs consisted of a phasic initial component followed by a fast activity oscillation in the beta range (20 Hz). To understand the neural mechanisms of odor-induced responses especially in the anterior PC, we analyzed odor-induced LFPs, together with unit activity data. We confirmed that the initial component of odor-induced response has a characteristic temporal pattern, generated by a relatively weak direct afferent input, followed by an intra-cortical associative response, which was associated with a phasic inhibition. The beta oscillation might be formed by the repetition of these network activities. These electrophysiological data were consistent with the results of previous studies that used slice or in vivo preparations, suggesting that the olfactory neural network and activities of the brain are preserved in our new in vitro preparation. This study provides the basis for clarifying the sequence of neural activities underlying odor information processing in the brain in vitro following natural olfactory stimulation.

Action Potentials↗

PubMed2006

Detection of eight antibodies in cancer patients' sera against proteins derived from the adenocarcinoma A549 cell line using proteomics-based analysis.

To screen cancer for specific autoantibodies, we applied the approach established by Brichory et al., who reported annexins I and II as specific antigens. Solubilized proteins from a cancer cell line (A549) were separated using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), followed by Western blotting (WB) analysis, in which the sera of individual patients were tested for primary antibodies. We found 11 positive spots on PVDF membrane using a WB/enhanced chemiluminescence detection Kit, and identified eight proteins, such as alpha-enolase, inosine-5'-monophosphate dehydrogenase, aldehyde dehydrogenase, 3-phosphoglycerate dehydrogenase, 3-oxoacid CoA transferase, chaperonin, peroxiredoxin 6 and triosephosphate isomerase, that reacted with these antibodies in patients' sera using MALDI-TOF/TOF. All eight antibodies were not detected in the sera derived from lung tuberculosis and healthy controls.

Adenocarcinoma↗

PubMed2006

Role of the thymus in transplantation tolerance in miniature swine: V. Deficiency of the graft-to-thymus pathway of tolerance induction in recipients of cardiac transplants.

BACKGROUND: We have previously shown that both thymic immigrants (graft to thymus pathway) and thymic emigrants (thymus to graft pathway) are involved in tolerance to renal allografts in miniature swine treated with a short course of calcineurin inhibitors. This study investigates the role of these pathways in cardiac transplant survival in recipients treated with a short course of tacrolimus. METHODS: Eleven animals received two-haplotype fully MHC-mismatched cardiac grafts with a 12-day course of tacrolimus. Recipients were thymectomized on day -21 (n=5) or day 0 (n=3), or were left euthymic (n=3). Two of the day -21 thymectomized animals received a day 0 host-MHC matched thymocyte infusion. RESULTS: Euthymic recipients of cardiac grafts treated with an immunosuppressive regimen identical to that previously shown to induce tolerance in euthymic recipients of renal allografts all rejected their grafts. Although no animal became tolerant, animals that were euthymic or thymectomized on day 0, as well as recipients of day 0 host-type thymocyte infusions following thymectomy on day -21, developed donor-specific hyporesponsiveness and maintained their cardiac grafts for markedly prolonged periods. In contrast, all animals thymectomized on day -21 that did not receive thymocyte infusions developed strong antidonor CTL responses and rejected their grafts by day 35. CONCLUSIONS: The graft-to-thymus pathway that plays an important role in tolerance induction to renal allografts appears to be relatively deficient in recipients of cardiac grafts. Strategies to increase donor antigen migration to the host thymus might therefore assist in tolerance induction to cardiac allografts.

Animals↗

PubMed2006

Isolation of the feline alpha1,3-galactosyltransferase gene, expression in transfected human cells and its phylogenetic analysis.

The enzyme alpha 1,3-galactosyltransferase (alpha1,3-GT), which catalyzes synthesis of terminal alpha-galactosyl epitopes (Gal alpha1,3Gal beta1-4GlcNAc-R), is produced in non-primate mammals, prosimians and new-world monkeys, but not in old-world monkeys, apes and humans. We cloned and sequenced a cDNA that contains the coding sequence of the feline alpha1,3-GT gene. Flow cytometric analysis demonstrated that the alpha-galactosyl epitope was expressed on the surface of a human cell line transduced with an expression vector containing this cDNA, and this alpha-galactosyl epitope expression subsided by alpha-galactosidase treatment. The open reading frame of the feline alpha1,3-GT cDNA is 1,113 base pairs in length and encodes 371 amino acids. The nucleotide sequence and its deduced amino acid sequence of the feline alpha1,3-GT gene are 88-90% and 85-87%, respectively, similar to the reported sequences of the bovine, porcine, marmoset and cebus monkey alpha1,3-GT genes, while they are 88% and 82-83%, respectively, similar to those of the orangutan and human alpha1,3-GT pseudogenes, and 81% and 77%, respectively, similar to the murine alpha1,3-GT gene. Thus, the alpha1,3-GT genes and pseudogenes of mammals are highly similar. Ratios of non-synonymous nucleotide changes among the primate pseudogenes as well as the primate genes are still higher than the ratios of non-primates, suggesting that the primate alpha1,3-GT genes tend to be divergent.

Amino Acid Sequence↗

PubMed2006

Long-term acceptance of fully allogeneic cardiac grafts by cotransplantation of vascularized thymus in miniature swine.

BACKGROUND: We have previously reported the ability of both thymokidney and vascularized thymic lobe (VTL) allografts to induce transplantation tolerance to renal allografts across a full major histocompatibility complex (MHC) mismatch in thymectomized miniature swine. However, whether vascularized thymus is capable of inducing tolerance to less tolerogeneic organs when it is transplanted simultaneously is not yet known. The present study investigates cardiac allograft survival and the mechanism of long-term acceptance in recipient swine following cotransplantation of VTL and cardiac grafts from fully MHC-mismatched donors. METHODS: Animals received a heart graft, a heart graft and a VTL, or a heart graft and a donor thymocyte infusion. Immunosuppressive regimens consisted of 12 or 28 days of tacrolimus. RESULTS: All animals that received a VTL maintained their grafts significantly longer than their counterparts that received only a heart graft, and those receiving 28 days of tacrolimus maintained their heart grafts long-term. Recipients of a donor thymocyte infusion demonstrated slightly prolonged cardiac graft survival but all rejected their grafts, highlighting the importance of thymic stroma. Cytotoxic T-lymphocyte responses against third-party antigens by cells from tolerant animals showed restriction by both self and donor MHC, whereas responses of controls were restricted to self MHC only. The presence of donor dendritic cells in the VTL grafts and results of co-culture assays suggest that both central and regulatory mechanisms were involved in achieving long-term acceptance. CONCLUSION: This is the first demonstration of the long-term acceptance of fully MHC-mismatched cardiac allografts in large animals.

Animals↗

PubMed2006

A transmembrane chemokine, CXC chemokine ligand 16, expressed by lymph node fibroblastic reticular cells has the potential to regulate T cell migration and adhesion.

Stromal cells in lymphoid tissues provide microenvironmental fields required for the triggering of efficient immune responses. Fibroblastic reticular cells (FRCs) are one of the integral constituents of such stromal fields; they construct the reticular network and are considered to regulate immune cells' behavior. However, the factors that mediate the interaction between lymphocytes and FRCs are poorly understood. Here we show that a mouse lymph node (LN)-derived FRC cell line, BLS4, expresses a transmembrane chemokine, CXC chemokine ligand (CXCL) 16, in response to tumor necrosis factor alpha (TNFalpha) and IFNgamma. TNFalpha-induced expression of CXCL16 depends on NFkappaB, p38 MAPK and PKA. Matrix metalloproteinase activity is required for producing soluble CXCL16 in the culture supernatant, likely via shedding at the juxtamembrane region of the extracellular domain. IL-12 enhances the expression of CXCR6 in anti-CD3/CD28-stimulated CD8+ T cells and their adhesion to the BLS4 cell surface in a TNFalpha-dependent fashion. The adherence is significantly inhibited in the presence of both anti-CXCL16 and anti-vascular cell adhesion molecule 1 (VCAM-1) antibodies. CXCL16 expression is also detected in the FRCs in LN sections and in gp38+VCAM-1+ FRCs isolated from LNs. Taken together, these findings suggest that CXCL16 is an important mediator of lymphocyte-stromal interaction within lymphoid tissues.

Animals↗

PubMed2006

Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation.

Studies of the human immune system have been limited by the lack of an appropriate in vivo model. For this reason, efforts have been made to develop murine models with a functional human immune system. We report here that cotransplantation of human fetal thymus/liver tissues and CD34(+) hematopoietic stem/progenitor cells led to the development of sustained human hematopoiesis and a functional human immune system in immunodeficient NOD/SCID mice. The humanized mice showed systemic repopulation with a comprehensive array of human lymphohematopoietic cells, including T cells, B cells, and dendritic cells, and the formation of secondary lymphoid organs. Furthermore, these mice produce high levels of human IgM and IgG antibodies and mediate strong immune responses in vivo as demonstrated by skin xenograft rejection. Thus, the humanized NOD/SCID mice described in this paper provide a powerful model system to study human immune function.

Animals↗

PubMed2006

Choroid plexus ependymal cells host neural progenitor cells in the rat.

We previously demonstrated that choroid plexus epithelial (modified ependymal) cells (CPECs) differentiated into astrocytes after grafting into the spinal cord. In the present study, we examined whether CPECs from rats at postnatal 1 day (P1), 7 day (P7), and 8 weeks (P8W) can function as neural progenitor cells that give rise to neurons and glial cells. Cell spheres were produced in cultures of whole tissue of the choroid plexus from the fourth ventricle of rats at each postnatal period. beta-tubulin class III (Tuj-1), glial fibrillary acid protein (GFAP)-, and O4-positive cells differentiated from cell spheres in the differentiation medium. We produced a monoclonal antibody 3E6 specifically labeling microvilli of CPECs. Using this monoclonal antibody, CPECs were isolated from the choroid plexus of P8W rats by cell sorter (FACS). Immunocytochemistry confirmed that there was no contamination from fibroblasts, endothelial cells, macrophages, or Schwann cells in the FACS-isolated 3E6-labeled cells. Cell spheres formed in the cultures of these 3E6-labeled CPECs. After expansion, these cell spheres gave rise to Tuj-1- (5%), GFAP- (45%), and O4-positive cells (0.16%). The remaining cells (45%) were unlabeled neural or glial markers. Some CPECs of the P8W rat were immunohistochemically stained with lineage-associated markers of Musashi-1 and epidermal growth factor-receptor (EGF-R). In addition, infusion of EGF or fibroblast growth factor-2 (FGF2) into the ventricle increased the number of bromodeoxyuridine (BrdU)-positive cells among CPECs from 0.03% (untreated) to 1.14% (38-fold, EGF) and 1.03% (35-fold, FGF2), respectively. These findings indicate that neural progenitor cells exist among CPECs in the rat.

Animals↗

PubMed2006

In ovo exposure quail assay for risk assessment of endocrine disrupting chemicals.

Although there are in vivo assays using various organisms for the risk assessment of chemicals with endocrine disrupting properties, effective experimental methods for avian species are still under debate. We have developed an in ovo exposure assay using Japanese quail eggs, aimed at assessing disrupting effects on avian reproductive development and function. Hybrid eggs from Brazilian Brown male and White Egg female quails, which can be genetically sexed by their plumage color after hatching, were prepared, and test materials dissolved in olive oil were injected into the air-chamber on day 10 of incubation. After sexual maturation of hatched chicks, we observed egg production by females and the egg quality and male-typical reproductive behavior, and then examined reproductive system morphology and serum steroid concentrations in both sexes. Treatment with a synthetic estrogen, diethylstilbestrol (DES, 0.5-50 ng/g egg), dose-dependently reduced the eggshell thickness and strength of eggs. A few females treated with 5 ng/g DES per egg produced soft-shelled/ unmarked eggs, and all laying females treated with 50 ng/g egg produced eggs completely lacking shells. DES also induced shortening of the left oviduct and abnormal development of the right oviduct in a dose-dependent manner, while testis weight was reduced symmetrically. In addition, 2,2',4',6'-tetrachlorobiphenyl-4-ol (10-1,000 ng/g egg), which previously showed relatively high estrogenic activity in vitro, caused dose-dependent shortening of the left oviduct and reduction in testis weight. The methods for evaluating endocrine disrupting effects and preparing experimental birds proposed in the present study are expected to facilitate assays for avian reproductive toxicology.

Animals↗

PubMed2006

Avian transgenerational reproductive toxicity test with in ovo exposure.

Ecological risk assessment of environmental pollutants requires effective laboratory assays and extrapolation of the resultant data to wild species. Because avian reproductive disorder and accumulation of persistent compounds in wild birds and their eggs have long been observed in polluted regions, we have developed an assay for investigating whether pollutants accumulated in eggs impair the reproduction of the exposed birds and the survival of the next generation using the Japanese quail. A typical estrogenic compound, diethylstilbestrol (DES), dissolved in olive oil was injected into the air-chamber of fertilized eggs on day 10 of incubation. After sexual maturation of hatched chicks, we mated pairs of male and female quails following an observation period of egg production and collected their eggs. The collected eggs were incubated and checked for the fertility and hatchability, and then the hatchlings were raised and observed in growth for 3 weeks. A dosage of 5 ng/g per egg of DES caused eggshell thinning in eggs laid by exposed females and reduction in eggshell strength. DES also induced shortening of the left oviduct and unexpected development of the right oviduct, while testis weight was reduced symmetrically. The ability of quail pairs to produce offspring was significantly diminished by exposure of females to DES independently of exposure of males, which mainly arose from production of abnormal and inviable eggs. Fertility of normal-shelled eggs and hatchability of fertilized eggs were unchanged regardless of treatments. External morphological abnormalities, which were mostly unopened toes of the foot, were frequently observed in hatchlings from exposed males independently of exposure of females. Additionally, we attempted to extrapolate the experimental results to the northern bobwhite and to predict population trends for quails in a polluted habitat using a population projection model composed of a combination of a Leslie matrix and the logistic equation. In the event of accumulation of an estrogenic compound equivalent to a dosage of 5 ng/g DES in quail eggs, the average population size was predicted to decrease by 20.2% after 1 year, to approximately half after 4 years, and to a fifth after 14 years. When observed weakening of individuals and the risk of egg breakage are taken into consideration, the decline in population was further accelerated. The proposed assay appears to be suitable not only for assessing adverse effects of chemicals on avian reproduction but for population projection of affected wild birds.

Abnormalities, Drug-Induced↗

PubMed2006

Pathology of renal xenograft rejection in pig to non-human primate transplantation.

Xenotransplantation has the potential to alleviate the critical shortage of organs for transplantation in humans. Miniature swine are a promising donor species for xenotransplantation. However, when swine organs are transplanted into primates, hyperacute rejection (HAR), acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR), and chronic xenograft rejection prevent successful engraftment. Developing a suitable regimen for preventing xenograft rejection requires the ability to accurately diagnosis the severity and type of rejection in the graft. For this purpose, histopathology remains the most definitive and reliable tool. We discuss here the characteristic features of xenograft rejection in a preclinical pig-to-non-human primate transplantation model. In miniature swine to baboon xenotransplantation, marked interstitial hemorrhage develops in HAR, and renal microvascular injury develops with multiple platelet-fibrin microthrombi in both HAR and AHXR. T-cell-mediated cellular immunity plays an important role in ACXR. Chronic humoral and cellular rejection may induce chronic xenograft rejection, and will be a major cause of graft loss in discordant xenotransplantation.

Acute Disease↗

PubMed2006

Discrepancy of performance among working memory-related tasks in autism spectrum disorders was caused by task characteristics, apart from working memory, which could interfere with task execution.

Working memory performance has been inconsistently reported in autism spectrum disorders (ASD). Several studies in ASD have found normal performance in digit span and poor performance in digit symbol task although these are closely related with working memory. It is assumed that poor performance in digit symbol could be explained by confirmatory behavior, which is induced due to the vague memory representation of number-symbol association. Therefore it was hypothesized that the performance of working memory task, in which vagueness did not cause confirmatory behavior, would be normal in ASD. For this purpose, the Advanced Trail Making Test (ATMT) was used. The performance of digit span, digit symbol and ATMT was compared between ASD and normal control. The digit span, digit symbol and ATMT was given to 16 ASD subjects and 28 IQ-, age- and sex-matched control subjects. The scores of these tasks were compared. A significantly lower score for ASD was found only in digit symbol compared with control subjects. There were no significant difference in digit span and working memory estimated by ATMT. Discrepancy of scores among working memory-related tasks was demonstrated in ASD. Poor digit symbol performance, normal digit span and normal working memory in ATMT implied that ASD subjects would be intact in working memory itself, and that superficial working memory dysfunction might be observed due to confirmatory behavior in digit symbol. Therefore, to evaluate working memory in ASD, tasks that could stimulate psychopathology specific to ASD should be avoided.

Adult↗

PubMed2006

[Effective measurement of coronary flow velocity reserve (CFVR) with transthoracic Doppler echocardiography (TTDE) for plasma cell leukemia with hyperviscosity syndrome].

A 67-year-old woman was admitted with impaired general performance, suffering from fatigue, chest oppression on exertion, and paresthesia of the finger trips. The laboratory findings showed increased white blood cells with abnormal cells, and serum immunofixation test showed monoclonal IgM kappa paraprotein. On flow cytometric immunophenotyping with CD38 gating, most of the abnormal cells expressed surface CD20, CD138, cytoplasmic IgM, but neither surface CD56 nor surface IgM. Immunohistochemical staining of abnormal cells was positive for surface CD38, surface CD20 and cytoplasmic IgM. The final diagnosis was plasma cell leukemia IgM kappa type. Electrocardiography (ECG) on admission showed ST depression in II, III, aV(F), V4, V5, and V6. Coronary angiography (CAG) is invasive and difficult for patients with renal failure, therefore the patient underwent transthoracic Doppler echocardiography (TTDE), which revealed reduced coronary flow velocity reserve (CFVR). Two courses of VAD therapy were administered, then the condition improved, the serum IgM level decreased, abnormal cells were decreased in peripheral blood and bone marrow aspirates, and the creatinine levels improved. With the return of normal ECG findings and improved CFVR, the abnormal ECG and reduction in CFVR was thought to be associated with the hyperviscosity syndrome in PCL. Noninvasive assessment of CFVR by TTDE is significantly useful for the patients who have renal failure and need chemotherapy.

Aged↗