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Biomedical subjects

M Yamaguchi

Publications and source records attributed to M Yamaguchi.

At least 73 records · Page 4Linked to original sources

Long-term outcome after allogeneic bone marrow transplantation for hematological malignancies with non-remission status. Results of a single-center study of 24 patients.

To investigate the problem of allogeneic bone marrow transplantation (allo-BMT) for advanced stage patients, we retrospectively analyzed 24 consecutive patients who underwent allo-BMT in the non-remission stage. Twenty-four patients (19 males and 5 females) with acute leukemia, chronic myelogenous leukemia, and malignant lymphoma underwent allo-BMT. The patients had a median age of 30 years. There were eight cases of acute myelogenous leukemia (AML), six cases acute lymphocytic leukemia (ALL), nine cases of chronic myelogenous leukemia (CML), and one case of Burkitt's lymphoma. The 3-year overall survival rate was 22.5%, with a median survival time of 206 days in AML, 345 days in ALL, and 363 days in CML. Overall survival was associated with a recovery of platelets of less than 30 days and an acute graft-versus-host disease (acute GVHD) presence of less than grade II ( p=0.042). Fourteen patients died of transplantation-related diseases. Our important problem is to decrease transplantation-related deaths in allo-BMT during the non-remission stage, and longer survival can be expected with better pretreatment and prophylaxis for GVHD. In addition, the selection of the source of hematopoietic stem cell transplantation at an optimal time is considered to be another problem to be approached.

Adolescent↗

Effects of rolipram on in vivo dopamine receptor binding.

In order to clarify whether changes in brain concentrations of the second messenger cyclic AMP (cAMP) affect in vivo receptor binding in the brain, the effects of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE(4)), on dopamine receptor binding in the mouse brain were studied. Rolipram significantly decreased in vivo (3)H-SCH 23390 (dopamine D(1) selective radioligand) binding in the mouse striatum in a dose-dependent manner. In vivo saturation experiments together with the kinetic analysis of (3)H-SCH 23390 binding revealed that the apparent association rate constant (k(on)) for (3)H-SCH 23390 binding rather than the maximum number of binding sites available (B(max)) was decreased by rolipram. (3)H-N-methylspiperone (NMSP, dopamine D(2) selective radioligand) binding in the mouse striatum was also decreased by rolipram whereas no significant changes in (3)H-raclopride (dopamine D(2) selective radioligand) binding were observed. As (3)H-raclopride binding has been reported to be much more sensitive than (3)H-NMSP binding to competition by endogenous dopamine, the decreases in (3)H-SCH 23390 and (3)H-NMSP binding cannot be attributed to competitive inhibition by endogenous dopamine. These results indicate that changes in second messenger cAMP concentrations may affect the apparent bimolecular association rate constant (k(on)) of dopamine receptor binding in intact brain. This may be mediated by changes in the receptor micro-environment and altered actual free ligand concentration surrounding the receptors.

3',5'-Cyclic-AMP Phosphodiesterases↗

Increased levels of a TH2-type CC chemokine thymus and activation-regulated chemokine (TARC) in serum and induced sputum of asthmatics.

BACKGROUND: Cytokines liberated by TH2 cells play crucial roles in the pathogenesis of bronchial asthma. Recent studies have demonstrated that CC chemokine receptor (CCR)4 is preferentially expressed by TH2 cells. These facts suggest possible involvement of two CCR4-specific ligands i.e., thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), in the pathogenesis of bronchial asthma via recruitment of TH2 cells to inflammatory sites. We investigated the levels of TARC and MDC in the serum and induced sputum of asthmatics. METHODS: The levels of TARC in the serum (46 asthmatics and 26 healthy subjects) and induced sputum (30 asthmatics and 6 healthy subjects) were measured using a highly sensitive ELISA system. The levels of eotaxin and MDC were also measured by ELISA. RESULTS: TARC, but not MDC, was significantly increased in asthmatic sera (P<0.001). Although MDC was undetectable in the sputum of most cases by our assay system, sputum TARC was significantly increased (P=0.027). CONCLUSIONS: The elevated TARC levels in asthmatics might be involved in the pathophysiology of asthma.

Adult↗

Treatment of pure red cell aplasia after major ABO-incompatible peripheral blood stem cell transplantation by induction of chronic graft-versus-host disease.

This report concerns a case of long-lasting pure red cell aplasia (PRCA) with a duration of 178 days after major ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). The patient needed red blood cell transfusion every week from day 54 following PBSCT. He showed no evidence of GVHD and the dose of cyclosporin A (CsA) was reduced rapidly from day 123, followed by the development of chronic GVHD around day 145. The patient no longer needed transfusions from day 167, the reticulocyte count began to increase on day 179, and antidonor isohemagglutinin titers became undetectable. Chronic GVHD induced by tapering of CsA thus appeared to be related to improvement in PRCA.

ABO Blood-Group System↗

Identification of ter94, Drosophila VCP, as a modulator of polyglutamine-induced neurodegeneration.

We have successfully generated a Drosophila model of human polyglutamine (polyQ) diseases by the targeted expression of expanded-polyQ (ex-polyQ) in the Drosophila compound eye. The resulting eye degeneration is progressive and ex-polyQ dosage- and ex-polyQ length-dependent. Furthermore, intergenerational changes in repeat length were observed in homozygotes, with concomitant changes in the levels of degeneration. Through genetic screening, using this fly model, we identified loss-of-function mutants of the ter94 gene that encodes the Drosophila homolog of VCP/CDC48, a member of the AAA+ class of the ATPase protein family, as dominant suppressors. The suppressive effects of the ter94 mutants on ex-polyQ-induced neurodegeneration correlated well with the degrees of loss-of-function, but appeared not to result from the inhibition of ex-polyQ aggregate formation. In the ex-polyQ-expressing cells of the late pupa, an upregulation of ter94 expression was observed prior to cell death. Co-expression of ter94 with ex-polyQ severely enhanced eye degeneration. Interestingly, when ter94 was overexpressed in the eye by increasing the transgene copies, severe eye degeneration was induced. Furthermore, genetical studies revealed that ter94 was not involved in grim-, reaper-, hid-, ced4-, or p53-induced cell death pathways. From these observations, we propose that VCP is a novel cell death effector molecule in ex-polyQ-induced neurodegeneration, where the amount of VCP is critical. Control of VCP expression may thus be a potential therapeutic target in ex-polyQ-induced neurodegeneration.

Adenosine Triphosphatases↗

The hormonal responses of lipoprotein lipase activity and lipolysis in adipose tissue differ depending on the stage of the estrous cycle in female rats.

OBJECTIVE: This study was designed to elucidate whether there were differences in the hormonal responses of the parameters involving triacylglycerol (TG) deposition and mobilization in adipose tissue among the stages of the estrous cycle in female rats. MEASUREMENTS: Adipose tissue was obtained from the parametrial region in female rats at each stage of the estrous cycle. Lipoprotein lipase (LPL) activity in the extracts of acetone/ether powders of the tissues was measured as a parameter for TG deposition. Norepinephrine-stimulated lipolysis in isolated fat cells was measured as a parameter for TG mobilization. RESULTS: LPL activity changed periodically during the estrous cycle; the activity level was highest at diestrus, began to decrease at proestrus, reached a minimum at estrus, began to increase again at metestrus-1, and increased further at metestrus-2. At diestrus and proestrus, LPL activity was increased with an increase in plasma insulin levels, suggesting that plasma insulin was the predominant up-regulator of LPL. But at estrus, metestrus-1 and metestrus-2, LPL activity remained low even when plasma insulin levels were high, indicating that it was not up-regulated by plasma insulin. Norepinephrine-stimulated lipolysis in fat cells was high at estrus and metestrus-1 and low at diestrus. CONCLUSION: The hormonal responses of LPL activity and lipolysis in adipose tissue differed depending on the stage of the estrous cycle.

Adipose Tissue↗

Horse lumbrical muscle: possible structural and functional reorganization in regressive muscle.

An anatomical study of horse lumbrical muscle (Lm) was carried out by light and electron microscopy in combination with immunochemical and cytochemical methods. Paraffin sections were subjected to haematoxylin and eosin (H & E) and Masson's trichrome staining for morphometric analysis. Paraffin sections were also used for immunostaining by anti-PGP 9.5 for reaction with nerve-protein associated-structures, anti-heat-shock protein 70 (hsp 70) for detection of gene expression changes, anti-fast myosin for the determination of muscle fibre types, and for detection of apoptotic gene expression of muscle fibres by the TUNEL method. The distribution of muscle fibre types on frozen sections was also examined by assaying ATPase (pH 4.2). We found that the proximal end of the tendon of the unipennate-shaped Lm binds to the deep digital flexor tendon, and the distal end of the Lm tendon connects to the medial surface of the palmar annular ligament. The Lm was not always present, but when found it varied in length greatly, up to 8 cm (muscle part alone), and weighed less than 1 g. The Lm was white, pale, or reddish in colour depending on the ratio of muscle fibre and connective tissue contents. The semi-tendinized regressive Lm was composed of rich vasculature, peripheral nerves, and nerve-like organs similar to the neuromuscular spindle (NMS). The extrafusal muscle fibres (e-lm) that surround the NMS were replaced with a thick outer capsule of connective tissues (CT) in the Lm nerve-like organ, which we named the neurotendinous capsule (NTC) organ. NTC organs exist alone or as multiple structures (up to eight) surrounded by a common outer capsule at the outermost CT ring. The NTC possesses several intrafusal muscle fibres (ifm) just as the NMS does. That the ifm was associated with nerve endings was confirmed by anti-PGP 9.5 and electron microscopic observation. Some muscle fibres in ifm and e-lm reacted with anti-fast twitch myosin and with anti-hsp 70. The e-lm exhibited at least two fibre types, determined by ATPase (pH 4.2) assay. The ifm exhibited mainly type I (slow twitch) fibres. No apoptotic gene expression was detected in either ifm or e-lm, suggesting the Lm is a vital organ. The degenerating fibres observed in ifm and e-lm indicate that the turnover rate of cytoplasmic components is accelerated. We attribute this phenomenon to the necessity for adaptation to new environmental demands. The surprising finding of tubular aggregates (TAs) in ifm of the NTC organ suggests that the Lm is continuously adapting. Some results related to variation in diameter of the collagen fibrils, isolation of the NTC organ and the myofibrillar protein constituents are also discussed. In conclusion, the so-called regressive Lm has rich vasculature, many peripheral nerves, and newly described NTC organs. The induction of heat-shock protein, lack of apoptotic gene expression in ifm and e-lm fibres, and TA formation in ifm suggest that horse Lm responds to environmental stress through reorganization and/or remodelling of cell constituents. We hypothesize that the horse Lm has lost its original role as a contractile element and changed to another function, likely as a vital nerve organ.

Animals↗

Interleukin-6 polymorphism (-634C/G) in the promotor region and the progression of diabetic nephropathy in type 2 diabetes.

AIMS: Interleukin-6 (IL-6) is a multifunctional cytokine produced by many different cell types, including glomerular mesangial cells. Recently, a novel C/G polymorphism at position -634 in the promotor region of the IL-6 gene has been reported. The aim of this study was to investigate whether the -634C/G polymorphism is associated with an increased risk for progression to diabetic nephropathy as well as elevated levels of IL-6 secretion by peripheral blood mononuclear cells. METHODS: The frequency of the -634C/G polymorphism was determined in Japanese patients with Type 2 diabetes and either normoalbuminuria (n = 162), microalbuminuria (n = 138), or macroalbuminuria (n = 154) by polymerase chain reaction-restriction fragment length polymorphism analysis. The level of IL-6 secretion in relation to genotype was assessed in lipopolysaccharide or advanced glycation end products-stimulated IL-6 secretion by peripheral mononuclear cells. RESULTS: The frequency of the -634G/G genotype and -634*G allele was significantly increased in the patients with macroalbuminuria compared with patients with normoalbuminuria (genotype: chi2 = 6.787, Pc = 0.0368; allele: chi2 = 9.080, Pc = 0.0104). Stepwise multiple regression analysis in these patients showed that hypertension (F = 40.48) and IL-6-634 gene polymorphism (F = 5.48) were the relevant variables for the progression of Type 2 diabetic nephropathy. Analysis of the IL-6 secretion data revealed that individuals carrying the -634*G allele had a higher IL-6 secretion capacity than those without the *G allele (P < 0.05). CONCLUSIONS: These results suggest that the IL-6-634C/G polymorphism may be a possible genetic susceptibility factor for the progression of diabetic nephropathy.

Diabetes Mellitus, Type 2↗

Reduction of survival and induction of chromosome aberrations in tobacco irradiated by carbon ions with different linear energy transfers.

PURPOSE: To determine the relationship between linear energy transfer (LET) and the relative biological effectiveness (RBE) for survival reduction and chromosome aberration induction in plants. MATERIALS AND METHODS: Tobacco seeds were exposed to carbon ions having LET ranging from 92 to 260 keV microm(-1). Survival ratc was determined at 7 weeks after sowing. Chromosome aberrations were observed when the root length reached about 0.5 mm (immediately after radicle emergence), 3 and 10 mm. RESULTS: The RBE for both endpoints increased with increasing LET and showed the highest value at 230 keV um(-1). The highest RBE was 65.0 for survival reduction and 52.5 for chromosome aberration induction. The types and yield ratio of chromosome aberrations such as fragments and bridges were not affected by radiation type at 0.5mm root length. As the roots elongated from 0.5 to 10 mm, the frequency of aberrant cells gradually decreased. The number of cells with fragments decreased faster than the number of cells with bridges. The decrement of chromosome aberrations appeared to be slower in roots irradiated by carbon ions than in roots irradiated by gamma-rays. CONCLUSIONS: The results show a close relationship between survival reduction and chromosome aberration induction in plants. The types and yield ratio of initial chromosome aberrations did not differ among gamma-rays and carbon ions with different LET.

Carbon↗

Ex vivo expansion of human UC blood primitive hematopoietic progenitors and transplantable stem cells using human primary BM stromal cells and human AB serum.

BACKGROUND: In vitro maintenance and expansion of human hematopoietic stem cells is crucial for many clinical applications, and investigators have been using xenogeneic, especially murine, stromal cells for stem-cell expansion. In addition, many such culture systems utilize FCS-containing medium or serum-free medium that contains human- or animal-derived proteins. However, the possible transmission of infectious diseases has led to a debate about the safety of the delivery of grafts expanded in culture using cells and proteins of allogeneic or xenogeneic origin. Using primary human BM stromal cells, we have established an AB serum-based co-culture system to expand human primitive progenitors and transplantable stem cells. METHODS: Cord blood CD34+ cells were cultured on a monolayer of human BM-derived primary stromal cells with thrombopoietin (TPO), stem-cell factor (SCF) and flt3/flk2 ligand (FL) in the presence of either FCS or AB serum. One to three weeks later, cells were examined for total cells, CD34+ cells, CD34+ CD38- cells, and clonogenic progenitors. SCID mouse reconstituting cell (SRC) activity was also studied. RESULTS: Three weeks of culture with TPO, SCF, and FL supported more than a 250-fold expansion of CD34+ cells, CD34+ CD38- cells and CFU-C, regardless of the kind of serum used. SRC assay revealed that transplantable stem cells were moderately expanded as well. DISCUSSION: This ex vivo expansion system should prove valuable in clinical settings in which stromal cells and serum are available from recipients or stem-cell donors.

ADP-ribosyl Cyclase↗

Characterization of the increase in bone 66 kDa protein component with healing rat fractures: stimulatory effect of zinc.

The characterization of protein components produced from bone tissues with fracture healing was investigated. Weanling rats were sacrificed between 1 and 7 days after the femoral fracture. Protein content in the femoral-diaphyseal tissues was markedly elevated by fracture healing. Moreover, when the femoral-diaphyseal tissues with fracture healing were cultured for 24 h in a serum-free medium, many proteins in the bone tissues were released into the medium. Analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that many protein molecules were released from the diaphyseal tissues with fracture healing. Especially, a protein molecule of approximately 66 kDa was markedly increased by fracture healing. This protein molecule was significantly increased, when the diaphyseal tissues with fracture healing were cultured in the presence of zinc acexamate (10(-6)-10(-4) M). Zinc acexamate (10(-4) M)-induced increase in medium 66 kDa protein molecule was significantly inhibited in the presence of actinomycin D (10(-7) M) or cycloheximide (10(-6) M). The zinc effect was completely blocked in the presence of PD98059 (10(-5) M), an inhibitor of MAPK kinase, or staurosporine (10(-6) M), an inhibitor of protein kinase C. The medium 66 kDa protein molecule was significantly elevated in the presence of parathyroid hormone (1-34) (10(-7) M), insulin-like growth factor-I (10(-8) M) or transforming growth factor-beta (10(-11) M), while 17beta-estradiol (10(-9) M) did not have an effect. The effect of these bone-stimulating factors was equal to the zinc effect. Zinc did not significantly enhance the effect of insulin-like growth factor-I in increasing medium 66 kDa protein molecule. The present study demonstrates that fracture healing increases production of the approximately 66 kDa protein molecule which is a major component produced from femoral-diaphyseal tissues of weanling rats, and that this elevation is enhanced by zinc treatment.

Animals↗

Primary repair of pulmonary artery sling with double outlet right ventricle and distal tracheal stenosis.

The fate of patients with pulmonary artery sling depends on associated tracheal lesions. Distal tracheal stenosis involving the carina frequently results in lethal obstruction due to secretion or inflammatory edema. Further-more, associated complex cardiac anomalies with excessive pulmonary flow make the situation more complicated. We present a case of successful simultaneous one-stage repair of pulmonary artery sling, double outlet right ventricle and distal tracheal obstruction. Pulmonary artery sling was relieved by relocation of the left pulmonary artery (left pulmonary artery to main pulmonary artery) and a tracheoplasty (resection and end-to-end anastomosis). We advocate early aggressive simultaneous repair of pulmonary artery sling with tracheal stenosis and concomitant repair of intracardiac anomalies whenever possible.

Abnormalities, Multiple↗

Nearest neighbour analysis of MCM protein complexes in Drosophila melanogaster.

The MCM proteins are a group of six proteins whose action is vital for DNA replication in eukaryotes. It has been suggested that they constitute the replicative helicase, with a subset of the proteins forming the catalytic helicase (MCM4,6,7) while the others have a loading or control function. In this paper we show that all six MCM proteins are present in equivalent amounts in soluble extracts and on chromatin. We have also analysed soluble and chromatin-associated MCM protein complexes under different conditions. This suggests that all six MCM proteins are always found in a complex with each other, although the interaction between the individual MCM proteins is not equivalent as stringent salt conditions are able to break the intact complex into a number of stable subcomplexes. These data contribute to the ongoing debate about the nature of MCM complexes, supporting the hypothesis that they act as a heterohexamer rather than as a number of different subcomplexes. Finally, using protein-protein cross-linking we have shown that MCM2 interacts directly with MCM5 and MCM6; MCM5 with MCM3 and MCM2; and MCM6 with MCM2 and MCM4. This provides the first direct information about specific subunit contacts in the MCM complex.

Animals↗

Involvement of nuclear transcription factor Sp1 in regulating glucose transporter-1 gene expression during rat trophoblast differentiation.

Glucose transporter-1 (GLUT1) is important in placental glucose transport. However, the mechanism of regulation of placental GLUT1 expression remains to be elucidated. We show here that the level of GLUT1 protein in rat choriocarcinoma cells (Rcho-1) decreased during differentiation. To analyze the regulatory mechanism of rat GLUT1 (rGLUT1) gene expression, we transfected rGLUT1 promoter-chloramphenicol acetyltransferase constructs into Rcho-1 cells. Deletion analysis of the rGLUT1 promoter suggested that the region -76/-53 bp was essential for basal transcriptional activity. Electrophoretic mobility shift assays showed that transcription factors Sp1 and Sp3 bound two GC boxes in the region -99/-33 bp of the rGLUT1 promoter. Mutation analysis of the Sp1 binding sites revealed that the promoter-proximal site located between -76 and -53 bp was essential for basal rGLUT1 promoter activity. Furthermore, the decreased level of GLUT1 may result from a decreased level of Sp1 during differentiation. These findings suggest that Sp1 is involved in the regulation of rGLUT1 gene expression during rat trophoblast differentiation.

Animals↗

Aggressive NK cell lymphoma/leukemia with clonal der(3)t(1;3) (q12;p25), del(6)(q13) and del(13)(q12q14).

We describe a 54-year-old man with CD2, CD7, and CD56-positive but CD3, CD4, and CD8-negative aggressive NK cell lymphoma/leukemia. Chromosome analysis of the peripheral blood cells showed clonal aberration consisting of 46,XY,dup(3)(p21p25),der(3)t(1;3)(q12;p25),del(5)(q13q22), del(6)(q13),del(13)(q12q14). The peripheral blood lymphoma cells contained clonal EBV-DNA by Southern blot analysis. The disease was refractory to chemotherapy and the clinical course was aggressive and rapid. Deletion 6q and deletion 13q have been frequently reported in NK cell lymphoma/leukemia. Thus, some tumor suppressor genes involving NK cell malignancies may be present in these regions.

Antigens, CD7↗

Pathogenesis of laryngeal narrowing in patients with multiple system atrophy.

1. We do not fully understand the pathogenesis of nocturnal laryngeal stridor in patients with multiple system atrophy (MSA). Recent studies suggest that inspiratory thyroarytenoid (TA) muscle activation has a role in the development of the stridor. 2. The breathing pattern and firing timing of TA muscle activation were determined in ten MSA patients, anaesthetized with propofol and breathing through the laryngeal mask airway, while the behaviour of the laryngeal aperture was being observed endoscopically. 3. Two distinct breathing patterns, i.e. no inspiratory flow limitation (no-IFL) and IFL, were identified during the measurements. During IFL, significant laryngeal narrowing was observed leading to an increase in laryngeal resistance and end-tidal carbon dioxide concentration. Development of IFL was significantly associated with the presence of phasic inspiratory activation of TA muscle. Application of continuous positive airway pressure suppressed the TA muscle activation. 4. The results indicate that contraction of laryngeal adductors during inspiration narrows the larynx leading to development of inspiratory flow limitation accompanied by stridor in patients with MSA under general anaesthesia.

Aged↗

Drosophila mitochondrial transcription factor A: characterization of its cDNA and expression pattern during development.

We cloned a cDNA for Drosophila mitochondrial transcription factor A (D-mtTFA) and characterized the recombinant protein. In Drosophila Kc cells, D-mtTFA was localized in the mitochondria, but not in the nucleus. By repetitive precipitation with His-tag and PCR amplification, the consensus nucleotide sequence for D-mtTFA-binding was determined to be 5'-TTATC/G. The binding sequence was found to be clustered in the A + T region of mitochondrial DNA which is suggested to be a replication origin and promoter region for light strand and heavy strand. We found a DNA replication-related element (DRE)-like sequence located upstream of the transcription initiation site of the D-mtTFA gene and obtained results indicating that DRE-binding factor (DREF) can bind to the DRE-like sequence of the D-mtTFA gene. The data suggest that transcription of the D-mtTFA gene is under control of the DRE/DREF regulatory system. Based on these results, the functions of D-mtTFA were discussed in relation to mitochondrial biogenesis of Drosophila melanogaster.

Animals↗