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Biomedical subjects

T Inukai

Publications and source records attributed to T Inukai.

At least 37 records · Page 2Linked to original sources

Clinical features of a polymorphism of the beta3-adrenergic receptor gene in patients with type 2 diabetes mellitus--a study using a pin-point sequencing method.

UNLABELLED: The human beta(3)-adrenergic receptor (beta(3)AR) is expressed specifically in adipose tissues, and its activation is activated in brown adipose tissues during thermogenesis and in white adipose tissues during lipolysis. We investigated the relationship between a polymorphism of the beta(3)AR gene and the clinical features of type 2 diabetes mellitus. Studies were conducted in 30 type 2 diabetic patients (15 males and 15 females). Analysis of polymorphisms of the beta(3)AR gene was performed by a pin-point sequencing method using the hair of the subjects. Preperitoneal (P-fat) and subcutaneous fat (S-fat) levels were determined by ultrasonography. We found a Trp(64)Arg allele of the beta(3)AR gene in the hair of 27% of all patients. The patients with this mutation showed a significantly younger onset-age of diabetes than those of the wild type. The body mass index, serum GPT levels, fasting immunoreactive insulin (IRI) and daily urinary C-peptide reaction (CPR) in the mutation group were markedly higher than in the wild type group. The P-fat, serum cholesterol and leptin concentrations tended to be higher in the mutation group. Patients in the mutation group had a significantly higher prevalence of hypertension (80%) compared with those in the wild type group (20%). CONCLUSIONS: The present results suggest that the clinical features of diabetic patients with a missense mutation in the beta(3)AR gene are substantially distinct from those of the wild type patients. These specific features include obesity, hyperinsulinemia, hypertension, and an increase in preperitoneal fat.

Adipose Tissue↗

The E2A-HLF oncoprotein activates Groucho-related genes and suppresses Runx1.

The E2A-HLF fusion gene, formed by the t(17;19)(q22;p13) chromosomal translocation in leukemic pro-B cells, encodes a chimeric transcription factor consisting of the transactivation domain of E2A linked to the bZIP DNA-binding and protein dimerization domain of hepatic leukemia factor (HLF). This oncoprotein blocks apoptosis induced by growth factor deprivation or irradiation, but the mechanism for this effect remains unclear. We therefore performed representational difference analysis (RDA) to identify downstream genetic targets of E2A-HLF, using a murine FL5.12 pro-B cell line that had been stably transfected with E2A-HLF cDNA under the control of a zinc-regulated metallothionein promoter. Two RDA clones, designated RDA1 and RDA3, were differentially upregulated in E2A-HLF-positive cells after zinc induction. The corresponding cDNAs encoded two WD40 repeat-containing proteins, Grg2 and Grg6. Both are related to the Drosophila protein Groucho, a transcriptional corepressor that lacks DNA-binding activity on its own but can act in concert with other proteins to regulate embryologic development of the fly. Expression of both Grg2 and Grg6 was upregulated 10- to 50-fold by E2A-HLF. Immunoblot analysis detected increased amounts of two additional Groucho-related proteins, Grg1 and Grg4, in cells expressing E2A-HLF. A mutant E2A-HLF protein with a disabled DNA-binding region also mediated pro-B cell survival and activated Groucho-related genes. Among the transcription factors known to interact with Groucho-related protein, only RUNX1 was appreciably downregulated by E2A-HLF. Our results identify a highly conserved family of transcriptional corepressors that are activated by E2A-HLF, and they suggest that downregulation of RUNX1 may contribute to E2A-HLF-mediated leukemogenesis.

Amino Acid Sequence↗

Downregulation of Bim, a proapoptotic relative of Bcl-2, is a pivotal step in cytokine-initiated survival signaling in murine hematopoietic progenitors.

Two distinct signaling pathways regulate the survival of interleukin-3 (IL-3)-dependent hematopoietic progenitors. One originates from the membrane-proximal portion of the cytoplasmic domain of the IL-3 receptor (betac chain), which is shared by IL-3 and granulocyte-macrophage colony-stimulating factor and is involved in the regulation of Bcl-x(L) through activation of STAT5. The other pathway emanates from the distal region of the betac chain and overlaps with downstream signals from constitutively active Ras proteins. Although the latter pathway is indispensable for cell survival, its downstream targets remain largely undefined. Here we show that the expression of Bim, a member of the BH3-only subfamily of cell death activators, is downregulated by IL-3 signaling through either of two major Ras pathways: Raf/mitogen-activated protein kinase and the phosphatidylinositol 3-kinase/mammalian target of rapamycin. Akt/phosphokinase B does not appear to play a significant role in this regulatory cascade. Bim downregulation has important implications for cell survival, since enforced expression of this death activator at levels equivalent to those induced by cytokine withdrawal led to apoptosis even in the presence of IL-3. We conclude that Bim is a pivotal molecule in cytokine regulation of hematopoietic cell survival.

Animals↗

Brain natriuretic polypeptide in type 2 NIDDM patients with albuminuria.

We investigated plasma brain natriuretic polypeptide (BNP) in Type 2 NIDDM patients with albuminuria. This study involved normal control subjects (Controls), hypertensive patients without diabetes mellitus (HT) and Type 2 NIDDM patients. Diabetic patients were divided into 4 groups by urinary albumin index (Alb-I): group I <30; group II 30-149; group III 150-300; group IV >300 mg/g creatinine. BNP levels in group III or IV were significantly higher than in Controls. The diabetic patients were re-divided into 4 groups (DM: with neither diabetic retinopathy (which was one of indicators of microangiopathy) nor hypertension, DM+HT: without diabetic retinopathy and with hypertension, DM+R: with diabetic retinopathy and without hypertension and DM+R+HT: with both diabetic retinopathy and hypertension). The Alb-I levels in DM+HT and DM+R+HT were significantly higher than the Controls, indicating the development of diabetic nephropathy in those groups. BNP levels in DM+HT, DM+R or DM+R+HT were significantly higher than in Controls. This indicates that BNP levels elevate in diabetic patients with increased albuminuria due to hypertension or microangiopathy deteriorating diabetic nephropathy. Elevated plasm BNP may play a pathophysiological role in the development of diabetic nephropathy.

Albuminuria↗

[Cord blood transplantation with two mismatched HLA loci in a child with acute lymphoblastic leukemia in second remission: follow-up of minimal residual disease using a clone-specific probe].

A 9-year-old girl with acute lymphoblastic leukemia in second remission underwent cord blood transplantation (CBT) from an HLA-mismatched (2 loci by serotype, 3 loci by genotype) unrelated donor. The infused nucleated cell count was 1.95 x 10(7)/kg. FK506 and mini-MTX were used to prevent graft-versus-host disease (GVHD), but grade II acute GVHD developed on the skin (stage III). The GVHD subsided after administration of corticosteroid, but marked hyperglycemia developed, which required transient insulin therapy for its control. Minimal residual disease (MRD) was assessed using a clone-specific probe for the JH region. MRD was positive before CBT, but became negative one month after CBT. Now, at 14 months after CBT, the patient is in a disease-free state without detectable MRD. These observations suggest that CBT with two mismatched HLA loci can be performed safely, and that sequential analysis of MRD is useful for evaluation of the disease status after CBT.

Blood Donors↗

[Transient myelodysplasia associated with human parvovirus B19 infection in a child without underlying disease].

Human parvovirus B19 (HPV-B19) infection is known to frequently induce aplastic crisis in patients with hemolytic anemia, but rarely causes hematological disorders in healthy subjects. We report a 5-year-old boy who showed transient myelodysplasia associated with HPV-B19 infection. He was admitted with severe nasal bleeding, and laboratory data showed marked thrombocytopenia (1,000/microliter), anemia (Hb: 8.4 g/dl), and mild leukopenia (3,000/microliter). A bone marrow smear revealed myelodysplastic changes in three cell lineages, but no giant proerythroblasts or megakaryocytes. The pancytopenia and myelodysplastic changes were resolved spontaneously within a week without any medication other than transfusion of red blood cells and platelets. Serological examination revealed an elevation of IgG antibody against HPV-B19 on days 15 and 120 and its subsequent decrease thereafter, although HPV-B19-specific DNA was not detected in the serum at onset. The clinical course and laboratory data suggest an etiologic role of HPV-B19 infection in the occurrence of transient myelodysplasia.

Child, Preschool↗

Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes.

We measured serum concentrations of advanced glycation endproducts (AGEs) in patients with type 2 diabetes, to elucidate the mechanisms underlying the elevated serum concentrations of AGEs and to clarify the relationship between serum AGE concentrations and the development of microangiopathy and macroangiopathy. Serum AGEs were significantly higher in diabetic patients than in age-matched control subjects (p < 0.0001). In diabetic patients, serum AGEs were positively correlated with HbAlc (r = 0.47, p < 0.0001), urinary albumin excretion (UAE) (r = 0.42, p < 0.0001), diabetes duration (r = 0.31, p = 0.0030), and fasting plasma glucose (r = 0.34, p = 0.0010). Multiple regression analysis disclosed that only the HbAlc and UAE levels independently correlated with serum AGE levels. Serum AGEs in diabetic patients with progressive retinopathy and overt nephropathy were significantly higher than in those with less severe retinopathy and nephropathy. Serum AGEs were significantly higher in the diabetic patients with coronary heart disease (CHD) than in those without CHD. These results suggest that the HbAlc and UAE levels are independent risk factors for increased serum AGE concentrations in type 2 diabetic patients, and that higher serum AGE concentrations are associated with increased severity of diabetic retinopathy and nephropathy. Serum AGE concentrations may be a useful marker not only for the severity of diabetic microangiopathy but also for the development of CHD in patients with type 2 diabetes mellitus.

Aged↗

Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes.

Serum concentration of soluble thrombomodulin (TM) is thought to be a marker for endothelial damage. Although several studies have reported that serum TM concentrations are increased in patients with diabetes mellitus, there is little information on the physiological function of soluble TM in human plasma. To evaluate the relationship of soluble TM in plasma between coagulation and/or fibrinolysis system in patients with diabetes, we measured plasma soluble TM, protein C activity (a natural anticoagulant induced by thrombin-TM complex), prothrombin F1+2 (a direct marker of thrombin generation), and plasmin-alpha 2-antiplasmin complex (PAP) and D dimer (measures of fibrinolytic activity) in 55 patients with type 2 diabetes mellitus. The plasma concentrations of soluble TM (P<0.01), protein C activity (P<0.01), prothrombin F1+2 (P<0.05), PAP (P<0.001) and D dimer (P<0.001) were significantly higher in the diabetic patients than the 48 age-matched control subjects. The plasma concentrations of TM and PAP were obviously increased in patients with diabetic nephropathy. In the diabetic patients, the plasma concentrations of soluble TM were inversely correlated with the protein C activity (r=-0.43, P<0.005), and were positively correlated with the plasma concentrations of prothrombin F1+2 (r=0.63, P<0.0001) and the plasma PAP concentrations (r=0.30, P<0.05). The present study demonstrated that both coagulation and fibrinolysis are enhanced concomitantly in patients with type 2 diabetes mellitus, and that an increase in plasma concentration of soluble TM is associated not only with hypercoagulability but also with enhanced fibrinolysis in diabetic patients.

Adult↗

Serum levels of carboxy-terminal propeptide of human type I procollagen are an indicator for the progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

The finding that glomerular mesangial cells produce human type I collagen suggests that the serum levels of carboxy-terminal propeptide of human type I procollagen (P1CP) may reflect the severity of diabetic nephropathy. We therefore investigated the relationship between serum P1CP levels and the extent of diabetic complications in 100 patients (46 males and 54 females) with Type 2 diabetes and in 64 healthy subjects. Serum P1CP was determined by radioimmunoassay. In diabetes, we defined P1CP levels less than 142 ng/ml as a normal P1CP group (group A), whereas we defined them as equal to or greater than 142 ng/ml as a high P1CP group (group B). The diabetic patients had significantly elevated serum P1CP levels compared with the controls. The prevalence of hypertension, proliferative diabetic retinopathy or macroalbuminuria was significantly higher in group B than in group A. Serum P1CP levels showed a significant positive correlation with urinary albumin excretion, but not with fasting blood glucose, glycosylated hemoglobin A(1c) or serum osteocalcin. Macroalbuminuric patients showed significantly higher P1CP levels than the normoalbuminuric patients. In patients in the absence of diabetic nephropathy, no significant differences of P1CP levels were found among the severity of diabetic retinopathy. The present results suggest that serum P1CP levels reflect the progression of diabetic nephropathy in patients with Type 2 diabetes.

Biomarkers↗

Participation of granulocyte colony-stimulating factor in the growth regulation of leukemia cells from Philadelphia chromosome-positive acute leukemia and blast crisis of chronic myeloid leukemia.

Granulocyte colony-stimulating factor (G-CSF) has been shown to support the growth of multipotential hematopoietic stem cells in addition to the cells of neutrophilic lineage. Philadelphia chromosome (Ph1)-positive leukemia has its origin in the hematopoietic stem cell. In the present study, we demonstrated that the proliferation of leukemic cells from chronic myeloid leukemia in blast crisis (CML-BC) and Ph1-positive acute lymphoblastic leukemia (ALL) cases is frequently stimulated with G-CSF in vitro. We next studied a total of 12 leukemic cell lines established from CML-BC (n= 6) and Ph1-positive acute leukemia (n= 6): four 'myeloid', five 'biphenotypic', and three 'lymphoid' types. All cell lines expressed G-CSF receptor (G-CSFR) in flow cytometric analysis, but their proliferative response to G-CSF in 3H-thymidine incorporation assay varied. The 'biphenotypic' cell lines expressed G-CSFR at higher levels and showed the most pronounced response to G-CSF. The 'lymphoid' cell lines showed intermediate G-CSFR expression with the modest response to G-CSF. Unexpectedly, 'myeloid' cell lines showed lower G-CSFR expression and lower G-CSF response compared with 'biphenotypic' cell lines. In three of four 'myeloid' cell lines, proliferation was partially inhibited by an addition of anti-G-CSF neutralizing monoclonal antibody into culture medium. Further, the % inhibition of 3H-thymidine uptake of cell lines positively correlated with the amount of their intracellular G-CSF measured by enzyme immunoassay, suggesting an autocrine growth mechanism via the G-CSF/G-CSFR interaction. These results suggest that G-CSF play an important role in the growth regulation of leukemia cells from Ph1-positive acute leukemia and CML-BC.

Blast Crisis↗

Expression of thrombopoietin receptor and its functional role in human B-precursor leukemia cells with 11q23 translocation or Philadelphia chromosome.

Thrombopoietin (TPO) is a hematopoietic growth factor which plays a central role in normal megakaryocytopoiesis and thrombopoiesis. Although the interaction between TPO and its receptor c-Mpl encoded by the c-mpl gene is now known to be implicated in the proliferation and/or differentiation of abnormal myeloid cells and normal hematopoietic stem cells, little is known about a role of the TPO/c-Mpl system in lymphoid leukemia cells. In the present study, we first examined the expression of c-mpl/c-Mpl in 23 human lymphoid leukemic cell lines (T-lineage 4, B-lineage 19) using three distinct methods. The c-mpl mRNA was detectable in as many as 20 cell lines (T-lineage 3, B-lineage 17) by reverse transcriptase-polymerase chain reaction, but its translated product, c-Mpl, was demonstrable by Western blot only in B-lineage cell lines. Flow cytometric analysis revealed the surface c-Mpl expression in 13 of 17 B-lineage cell lines, but its higher expression (>40%) was restricted in nine B-precursor cell lines, eight of which had 11q23 translocation or Philadelphia chromosome (Ph1). We also demonstrated that two of eight cell lines with 11q23 translocation or Ph1 exhibited a significant proliferative response to TPO in the 3H-thymidine uptake and colony-forming assays. Triggering of these cell lines by TPO transiently up-regulated tyrosine phosphorylation of JAK-2 and Shc, indicating that their receptor is functional. Primary leukemia cells separated from patients with B-precursor acute lymphoblastic leukemia with Ph1 or 11q23 translocation also showed the surface c-Mpl expression and a significant responsiveness to TPO. These results suggest that the TPO/c-Mpl interaction may play a physiological role in the growth regulation of B-precursor leukemia cells particularly with specific chromosomal abnormalities.

Antigens, Surface↗

Thermographic measurement of skin temperature recovery time of extremities in patients with type 2 diabetes mellitus.

To elucidate the relationship between the recovery of skin temperature in an extremity after exposure to cold water and various factors associated with diabetes, we measured skin temperature in type2 diabetic patients (N=61) and control subjects (N=16). A thermo-tracer was used in thermographic measurements. The right third toe of each subject was immersed in cold water at 0 degrees C for 10 sec. Rt represents the recovery rate of skin temperature at t min after exposure. Rt was significantly reduced in the diabetic patients every 5 min in the 20 min period following exposure compared with control subjects. The diabetic patients group exhibited a significantly positive correlation between R20 and the ankle-brachial index. R20 in the diabetic patients showed a significantly positive correlation with the reduction in systolic blood pressure at the arm observed in Schellong's test. In addition, R20 showed a significantly negative correlation with plasma levels of fibrinogen and plasminogen activator inhibitor-1. However, the severity of diabetic retinopathy and nephropathy was not significantly related to R20 in the diabetic patients. The present data indicate that the recovery of skin temperature after immersion in cold water was markedly reduced in patients with type 2 diabetes mellitus as compared with healthy control subjects. Peripheral arteriosclerosis, impaired sympathetic nerve function and the activation of the blood coagulation system may all contribute to this reduced recovery of skin temperature.

Analysis of Variance↗

Anatomical variants in the floor of the third ventricle; implications for endoscopic third ventriculostomy.

Longstanding hydrocephalus and raised intracranial pressure can lead to unusual anatomical variants in the floor of the third ventricle, which may be important when performing endoscopic third ventriculostomy. Two middle aged patients with symptomatic longstanding hydrocephalus had scans that showed ventricular hydrocephalus, an empty sella, and a dilated infundibular recess which herniated into the sella turcica. Endoscopic third ventriculostomy confirmed that instead of the tuber cinerum and infundibular recess, the anterior inferior floor of the third ventricle was hanging down ventral to the pons into the sellar floor. Third ventriculostomy to the prepontine cistern was made on the dorsal wall of the dilated infundibular recess to the area surrounded by the dorsum sellae, the basilar artery trunk, and the left superior cerebellar artery, with good symptomatic control. Association of the empty sella and persistence of the infundibular recess must be carefully evaluated by MRI before attempting endoscopic third ventriculostomy. Herniation of the anterior inferior floor of the third ventricle into the empty sella can lead to loss of anatomical landmarks that require special attention during third ventriculostomy.

Adult↗

Analysis of intragenic recombination at wx in rice: correlation between the molecular and genetic maps within the locus.

In plant genomes as well as other eukaryotic genomes, meiotic recombination does not occur uniformly. At the level of the gene, high recombination frequencies are often observed within genetic loci in maize, but this feature of intragenic recombination is not seen at the csr1 locus in Arabidopsis. These observations suggest that meiotic recombination in plant genomes varies considerably among species. In the present study we investigated meiotic recombination at the wx locus in rice. The mutation sites of wx mutants induced by ethyl methanesulfonate (EMS) treatment or gamma-ray irradiation and a spontaneous wx mutant were physically characterized, and the genetic distances between those wx mutation sites were estimated by pollen analysis. Based on these results, the recombination frequency at the wx locus in rice was estimated as 27.3 kb/cM, which was about 10 times higher than the average for the genome, suggesting that there was a radically different rate of meiotic recombination for intra- and intergenic regions in the rice genome.

Alleles↗

[A boy with summer onset paroxysmal cold hemoglobinuria induced by Donath-Landsteiner antibody with anti-I specificity].

We encountered 4-year-old boy who developed paroxysmal cold hemoglobinuria (PCH) in the middle of August. He was admitted due to progressive jaundice and pallor following fever and nausea. Laboratory data revealed severe anemia, increased serum indirect bilirubin and LDH, and decreased serum haptoglobin. Direct/indirect Coombs tests were positive. These findings yielded a diagnosis of autoimmune hemolytic anemia. Serological test for syphilis was negative. The patient's symptoms and signs promptly subsided after treatment with prednisolone, which was started on the 2nd hospital day. The patient has been in a disease-free state for 16 months without any medication. After discharge, he was finally given a diagnosis of PCH because a Donath-Landsteiner test was positive. The antibody belonged to an IgM subclass and showed anti-I specificity. Considering that development of PCH is common in winter, this case was unique because it developed in August. We speculated that exposure to a cool air-conditioned atmosphere prior to hospitalization and the cooling mechanism of the body after admission were involved in the summer onset of PCH and its prolonged clinical course.

Air Conditioning↗

Aldose reductase mRNA expression is associated with rapid development of diabetic microangiopathy in Japanese Type 2 diabetic (T2DM) patients.

There appears to be an obvious difference in the susceptibility to diabetic microangiopathy among Type 2 diabetic (T2DM) patients. We examined the hypothesis that aldose reductase (AR) messenger ribonucleic acid (mRNA) expression may be enhanced in diabetic patients susceptible to diabetic microangiopathy by measuring AR mRNA expression in the polymorphonuclear leukocytes (PMNs) obtained from T2DM patients. The AR mRNA and beta-actin mRNA expressions were measured by reverse transcription-polymerase chain reaction method. The relative AR mRNA expression to beta-actin mRNA expression significantly increased in the PMNs of T2DM patients, compared to normal healthy controls. The relative AR mRNA expression tended to increase with an increase of glycosylated haemoglobin A1c (HbA1c) levels. The patients who showed both progressive diabetic retinopathy and diabetic neuropathy within 10 years after the diagnosis of T2DM (Group I) showed significantly 1.6 times higher AR mRNA expressions than those who have not shown both complications over 10 years after diagnosis (Group II), in spite of no obvious difference in glycaemic control between both groups. The present data indicate that the AR mRNA expression increased in the PMNs of T2DM patients and there is an obvious difference in the PMNs AR mRNA expression between T2DM patients susceptible and relatively resistant to the development of diabetic microangiopathy.

Aged↗

Insulin resistance and changes in the blood coagulation-fibrinolysis system after a glucose clamp technique in patients with type 2 diabetes mellitus.

We investigated the relationship between changes in insulin resistance and blood coagulation-fibrinolysis following institution of a glucose clamp (GC) in patients with type 2 diabetes mellitus. We studied 35 type 2 diabetic patients (19 males and 16 females, mean age at 58.3 +/- 11.9 years) and 10 healthy subjects. The hyperinsulinemic euglycemic GC technique was performed using on artificial pancreas. The degree of insulin resistance was determined from the glucose infusion rate (GIR) calculated from the GC technique. The GIR in type 2 diabetic patients was markedly reduced compared to that in healthy subjects. The GIR was significantly and negatively correlated with the body mass index and the serum concentrations of the fasting immunoreactive insulin (FIRI). The plasma concentrations of thrombomodulin (TM) and tissue plasminogen activator (tPA) in the diabetic patients were significantly higher than those in the healthy subjects. The plasma concentrations of plasminogen activator inhibitor 1 in the diabetic patients tended toward higher than those in the healthy subjects. The elevated plasma concentrations of TM and tPA in diabetes were significantly lowered following a GC technique. Patients with advanced nephropathy had significant higher concentrations of TM and tPA compared to healthy subjects. We concluded that diabetic patients have abnormalities in the blood coagulation-fibrinolytic system that can be improved by the GC technique.

Albuminuria↗

Analysis of serum lactate dehydrogenase and its isozymes during administration of granulocyte colony-stimulating factor in children.

Serum lactate dehydrogenase (LDH) activity is known to become elevated following granulocyte colony-stimulating factor (G-CSF) therapy in some patients, but no extensive studies on this phenomenon have been performed. In 26 children with malignancies in complete remission who received recombinant human G-CSF intravenously after combined chemotherapy, we measured serum LDH and its isozymes (81 episodes) before chemotherapy (pre-Tx), during administration of G-CSF (mid-Tx), and after stopping G-CSF (post-Tx) and compared the obtained data using paired t test. Twelve episodes were excluded from analysis because of liver dysfunction (alanine aminotransferase > 45 IU/L). Serum LDH at mid-Tx (343.1+/-19.8 IU/L; mean +/- SE) was significantly higher than that at pre-Tx (186.9+/-6.7 IU/L) and post-Tx, but this difference was observed only when change in white blood cell counts (WBCs) (WBC at mid-Tx minus WBC at pre-Tx) was greater than or equal to 4000/microL (58 episodes). Percentages of LDH isozymes 3, 4, and 5 at mid-Tx (23.5+/-1.0, 11.7+/-0.8, and 8.3+/-0.7) were significantly increased compared with those at pre-Tx (19.5+/-0.7, 6.3+/-0.3, and 4.2+/-0.5) and post-Tx, resulting in a significant decrease in percentages of LDH isozymes 1 and 2 at mid-Tx. In episodes of change in WBCs > or =4000/microL, change in LDH significantly correlated to changes in WBCs and granulocytes but not to change in lymphocytes or monocytes. These results suggest that serum LDH is significantly elevated during G-CSF administration in accordance with the increase in peripheral granulocytes, which accompanies change in the pattern of percentages of LDH isozymes.

Adolescent↗