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Biomedical subjects

K Kojima

Publications and source records attributed to K Kojima.

At least 217 records · Page 12Linked to original sources

Graft rejection and recovery of host-derived hematopoiesis after allogeneic bone marrow transplantation: relation to conditioning with high dose etoposide and total body irradiation.

Engraftment failure following allogeneic bone marrow transplantation (BMT) is rare in patients with acute leukemia, after frequent conditioning with marrow-lethal chemoradiotherapy. We evaluated the efficacy of a preparatory regimen consisting of fractionated total body irradiation (TBI) (12 Gy in six fractions) and high dose etoposide (60 mg/kg) administered as an 8-h infusion for allogeneic BMT in 16 consecutive patients with acute leukemia. Although 14 patients showed complete and sustained engraftment, the remaining two patients rejected bone marrow grafts from HLA-identical sibling donors and showed subsequent recovery of host-derived hematopoiesis. Despite the limited number of patients, this observation suggests that the immunosuppressive potential of etoposide may be inferior to that of cyclophosphamide (CY) and that etoposide as an alternative to CY as an antileukemic and immunosuppressive agent in allogeneic BMT may increase the risk of graft rejection.

Acute Disease↗

14q11 abnormality and trisomy 8q are not common in Japanese T-cell prolymphocytic leukemia.

We studied ten cases of Japanese T-cell prolymphocytic leukemia (T-PLL) collected over the last 9 years. Median age was 61 years with a male predominance (M:F, 8:2). The main disease features were splenomegaly, lymphadenopathy, hepatomegaly, skin lesions and serous effusions. The clinical course was progressive with a median survival of 10 months. Immunophenotyping showed that the prolymphocytes had a post-thymic phenotype (TdT-, CD1a-, CD2+, CD3+, CD5+, CD7+) with a predominant CD4+ immunophenotype. Cytogenetic analysis showed no consistent abnormalities. 14q abnormality and trisomy 8q, which are frequently seen in T-PLL of Western countries, were found in only two and zero cases, respectively. We conclude that the clinical and biological characteristics of T-PLL in Japan are almost the same as those in Western countries. However, the cytogenetic findings of T-PLL in Japan might be different.

Adult↗

Deleted HTLV provirus in peripheral blood cells of a patient with T-cell prolymphocytic leukaemia.

We describe the first case of T-cell prolymphocytic leukaemia (T-PLL) in which the peripheral blood cells contained a human T-lymphotropic virus (HTLV) related tax sequence. Serum screening tests for anti-HTLV-I/II antibodies were negative. Polymerase chain reaction disclosed the presence of an HTLV-I tax sequence in the peripheral blood. Other sets of oligonucleotide primers for HTLV-I gag, pol, env and the long terminal repeat regions and for the HTLV-II pol region were negative in the DNA of the cells. Although patients with T-PLL have been reported to be seronegative for HTLV-I, our findings point to the possibility that HTLV-I infection might be involved in the aetiology of at least some cases of T-PLL and that there may be alternative mechanisms involved in HTLV-associated leukaemogenesis.

Base Sequence↗

Dipyridamole and dilazep suppress oxygen radicals in puromycin aminonucleoside nephrosis rats.

BACKGROUND: Reactive oxygen species (ROS) are involved in the pathophysiology of puromycin aminonucleoside (PAN) nephrosis. To elucidate further the role of radicals in PAN nephrosis and the to determine the particular radical species scavenged by dipyridamole (DPM) and dilazep (DZ), we applied chemiluminescence and electron spin resonance (ESR) techniques. METHODS: Chemiluminescence of glomeruli, which were isolated on day 7 from rats injected with 100 mg kg-1 PAN, was measured with or without scavengers. The inhibitory effects of DPM and DZ on hydroxyl radical adduct formation in the Fenton's reaction were evaluated using ESR. RESULTS: Chemiluminescence was greater in glomeruli from rats with PAN nephrosis than in the the glomeruli of control rats. This increase was suppressed by superoxide dismutase, catalase, dimethylthiourea and also by DPM and DZ. ESR indicated that DPM and DZ inhibited hydroxyl radical adduct formation with a second-order rate constant of 2.9 x 10(10) and 1.6 x 10(10) (mol L(-1) s(-1) respectively, similar to that of dimethylthiourea. CONCLUSION: DPM and DZ scavenge hydroxyl radicals, thereby alleviating PAN nephrosis.

Animals↗

Improvement with disodium cromoglycate of neutrophil phagocytosis and respiratory burst activity in a patient with hyperimmunoglobulin E syndrome.

We report a case of hyperimmunoglobulin E syndrome (HIE) complicated by neutrophil deficiency which was successfully treated with oral administration of disodium cromoglycate. A 48-year-old Japanese man with HIE developed Streptococcus pneumoniae meningitis. Laboratory tests after the meningitis revealed persistent neutropenia (300-800/mm3) and defects of phagocytosis and bacterial killing by neutrophils. Administration of disodium cromoglycate was started, and neutrophil counts gradually increased to 1200-1600/mm3. The impaired neutrophil activities returned to normal. The patient improved clinically; during the 2-year treatment, he had only two brief episodes of the common cold. Disodium cromoglycate may have potential clinical use in the treatment of cases of HIE even with neutrophil deficiency.

Cromolyn Sodium↗

Activation of the Ca2+-activated K+ channel via protein kinase A-dependent phosphorylation in human prostatic smooth muscle cells.

BACKGROUND: We investigated the functional importance of the Ca2+-activated K+ channel (K(Ca)-channel) of human prostatic smooth muscle cells in cyclic adenosine 3',5'-monophosphate (cAMP)-induced relaxation, to clarify signal transduction pathways and intracellular mechanisms of relaxation in prostatic smooth muscle. METHODS: Using the patch-clamp technique, we characterized the K(Ca)-channel of cultured human prostatic smooth muscle cells. We also investigated the effects on the K(Ca)-channels of forskolin, an activator of adenylate cyclase, amrinone, a phosphodiesterase inhibitor, and protein kinase A (A-kinase)-dependent phosphorylation. RESULTS: Single-channel current recordings from cultured human prostatic smooth muscle cells revealed the presence of K(Ca)-channels (conductance 296.7 +/- 5.67 pS, n = 7). In cell-attached patch configurations, the K(Ca)-channel was activated by forskolin (10(-4) mol/L) and amrinone (10(-4) mol/L). In inside-out patch configurations, it was activated by catalytic subunits of A-kinase (10 U/mL). CONCLUSIONS: We conclude that the K(Ca)-channel of human prostatic smooth muscle cells is regulated by intracellular cAMP levels and that A-kinase mediates the cAMP-induced activation of the K(Ca)-channel. This regulation of the K(Ca)-channel by cAMP may at least partially explain cAMP-induced prostatic smooth muscle relaxation and the effectiveness of certain drugs for treatment of obstruction in benign prostatic hyperplasia.

Adenylyl Cyclases↗

Aortic and lower-extremity arterial disease: evaluation with MR angiography versus conventional angiography.

PURPOSE: To compare magnetic resonance (MR) angiography with conventional angiography in evaluation of the aorta and lower-extremity arterial system. MATERIALS AND METHODS: Fifty-seven patients were evaluated with femoral conventional and MR angiography. Iliac artery segments were evaluated with two-dimensional and contrast material-enhanced three-dimensional time-of-flight MR angiography. Infrainguinal regions were evaluated with two-dimensional time-of-flight MR angiography with a dedicated lower-extremity coil. Arteries depicted on femoral images were separately interpreted as 20 anatomic segments. Disease classification included normal to moderate disease (0%-50% stenosis), severe stenosis (> 50% stenosis), diffuse disease (more than one severe stenosis), and occlusion. Four readers interpreted the images and rendered treatment recommendations. RESULTS: Substantial to almost perfect interobserver agreement (kappa, 0.66-1.00) was achieved in most cases for MR angiogram interpretation. The three most experienced readers achieved substantial to almost perfect intraobserver agreement (kappa, 0.61-1.00) between conventional and MR angiogram interpretation in most cases. Among three readers, moderate agreement (kappa, 0.43-0.53) was found between treatment recommendations based on conventional versus MR angiographic findings; for the most experienced reader, this agreement was almost perfect (kappa, 0.90). CONCLUSION: For experienced readers, there was substantial to almost perfect agreement between conventional and MR angiographic image interpretations of the aorta and lower-extremity arterial system.

Aged↗

Biphasic action of phenylephrine on the Ca(2+)-activated K+ channel of human prostatic smooth muscle cells.

The elevation of cytosolic Ca2+ ([Ca2+]i) is known to regulate smooth muscle contractility. A physiological concentration of phenylephrine induced the elevation in [Ca2+]i of human prostatic smooth muscle cells; however, contraction of prostatic tissues in vitro needs a higher concentration of phenylephrine than the physiological level. To investigate this discrepancy, we investigated the functional importance of the Ca(2+)-activated K+ channel (KCa channel) of human prostatic smooth muscle cells in phenylephrine-induced contraction. Using the patch-clamp technique, the KCa channel of human prostatic smooth muscle cells was activated by phenylephrine at a physiological concentration (10(-7)-10(-5) M) but was inhibited at a higher concentration (10(-4)-10(-3) M). Phenylephrine (10(-3) M) also inhibited the KCa channel which was activated by 10 microM A23187, a calcium ionophore. Similar inhibition was obtained with 1 microM phorbol 12-myristate 13-acetate, an activator of protein kinase C (C-kinase). Both inhibitions were reversed by subsequent application of 1 nM staurosporine, a protein kinase inhibitor. These results suggested that C-kinase mediated the phenylephrine-induced inhibition of the KCa channel. In this study, a physiological concentration of phenylephrine induced activation of the KCa channel of human prostatic smooth muscle cells, which brought about membrane hyperpolarization and relaxation of human prostatic smooth muscle cells. The regulation of the KCa channel by phenylephrine may explain the need of a high concentration of phenylephrine for the contraction of prostatic tissue.

Adrenergic alpha-Agonists↗

Effects of oxygen and carbon dioxide on mean cell volume.

Changes in mean cell volume (MCV) following addition of CO2, O2 or both to venous blood treated with ethylenediaminetetraacetic acid were studied in an attempt to evaluate the effects of saturation with these gases. The MCV before the addition was taken to be 100%. When CO2 was mixed with each of 353 samples, the mean increase (+/- SD) was 6.10 +/- 1.72%. When O2 was added to 335 specimens, the mean decrease was 1.42 +/- 0.96%. When first CO2 and then O2 was added to 266 samples, the mean change (the sum for each sample of the absolute value of the increase plus that of the decrease) was 7.39 +/- 1.90%. Results of samples of venous and arterial blood from 15 subjects were compared to check these observations in vivo. The MCV of venous blood was always larger than that of arterial blood.

Adolescent↗

Long-term administration of "sho-saiko-to" increases cytochrome P-450 mRNA level in mouse liver.

Simplified differential display of mRNA was applied to isolate and identify genes transcriptionally regulated in mouse liver by sho-saiko-to administration. A cDNA fragment up-regulated by sho-saiko-to was isolated and characterized. cDNA sequencing and subsequent database analysis revealed that the fragment showed significant sequence similarity with mouse testosterone 16-alpha-hydroxylase (cytochrome P-450[16alpha]) cDNA. The increased level of mRNA expression of cytochrome P-450(16alpha) in association with sho-saiko-to administration suggests the molecular mechanism of the chemopreventive effect of sho-saiko-to. This result indicates the usefulness of the mRNA differential display technique to investigate the molecular mechanism of Kampo medicine.

Animals↗

Evaluation of shikonin on granulation tissue formation compared with carrageenan.

The effect of shikonin (SK) on granulation tissue formation was biochemically evaluated and the biological effect of SK on cotton pellet induced granulation tissue formation and the induction of hind paw edema was compared with that of lambda-carrageenan (carrageenan) in rats. The dry weight of granulation tissue formed was increased by SK. The amounts of hemoglobin and hydroxyproline in granulation tissue were also increased by SK. These results suggest that SK has an enhancing effect on the formation of granulation tissue, accompanied by the proliferation of capillaries and the increased production of collagen in rats. SK showed mild stimulation toward swelling when injected into the hind paws of rats, as did carrageenan, while it showed a marked enhancing effect on granulation tissue formation compared with carrageenan. These results suggest that the mechanism underlying the biological effect of SK on granulation tissue formation is different from that of carrageenan, though the mild stimulation by SK might still contribute in part to the enhancing effect on granulation tissue formation.

Animals↗

The average unwinding angle of DNA duplex produced by the binding of chromomycin A3.

The effect of chromomycin A3 binding on the geometry of DNA duplex (plasmid pBR322) has been examined using topoisomerase I relaxation followed by gel electrophoresis. To determine the equilibrium constant of this drug-DNA binding-dissociation reaction in the same concentration range (ca. 10(-5) M) in the same buffer as those for the topoisomerase reaction (at 37 degrees C), fluorescence measurements were made of the same plasmid-drug system, followed by a Scatchard plot and an analysis using McGhee-von Hippel's exclusion site model. The binding constant has been found to be 3.8 x 10(5) M-1 in the particular buffer (buffer-T) at 37 degrees C, and the number of base pairs involved in the site of one chromomycin molecule on the duplex has been found to be 5. It has been concluded that one chromomycin molecule, bound to the duplex, unwinds it by 11.8 +/- 1.1 degrees. In addition, the enthalpy of binding was determined to be 31.81 kJ/mole using a titration calorimeter with a more concentrated (6.2 mM) solution.

Algorithms↗

Utility of measuring serum parathyroid hormone-related protein concentration in leukemic patients with hypercalcemia for assessing disease status.

OBJECTIVE: To evaluate serum parathyroid hormone-related protein (PTHrP) as a marker of hypercalcemia in leukemic patients. DESIGN AND METHODS: We measured the serum levels of PTHrP, lactate dehydrogenase (LDH) and calcium in three patients with hypercalcemia due to leukemia. RESULTS: Serum levels of PTHrP, LDH and calcium were elevated at admission in all patients, and these levels were reduced to within the normal range after chemotherapy. However, normalization of serum PTHrP concentration occurred more rapidly than normalization of serum LDH levels after chemotherapy. The increase in serum PTHrP concentration accompanied leukemic cell proliferation and preceded the increases in serum LDH and calcium. Serum LDH concentration increased, but serum PTHrP concentration did not after administration of granulocyte colony-stimulating factor. CONCLUSION: These findings suggest that serum PTHrP may be a more useful marker than serum LDH or calcium in assessing the status of leukemic patients with hypercalcemia.

Biomarkers↗

Source of reactive oxygen species in anti-Thy1 nephritis.

In proliferative glomerulonephritis, both macrophages and mesangial cells generate reactive oxygen species (ROS), contributing to the development of glomerular injury. We have attempted to determine which cell produces ROS during anti-Thy1 nephritis (ATN) in rats. The generation of ROS was studied using luminol amplified chemiluminescence (GCL) on isolated glomeruli. Immunohistochemical studies used avidin-biotin complex (ABC) to label macrophages and mesangial cells. Immediately after ATN induction, mesangiolysis and infiltration with ED-1 positive cells (referred to as macrophage) was noted with a peak at day 1. After day 4, mesangial proliferation appeared with a decrease of the ED-1 positive cells and a prominent increase of PCNA positive cells (regarded as mesangial cells). In the early phase of ATN, GCL, reflecting ROS generation, increased along with the appearance of ED-1 positive cells. GCL subsequently decreased as mesangial cells increased. This suggested that macrophage were the principal participants in ROS generation in the early phase of ATN although mesangial cells cannot be completely disregarded in the generation of ROS and development of glomerular injury.

Animals↗

Synthesis and structure-activity relationships of 1beta-methylcarbapenems with quaternary ammonium side chains.

The synthesis and antibacterial activity of 1beta-methylcarbapenems with quaternary ammonium groups at the C-2 position have been studied. Two types of new carbapenem derivatives have been synthesized. These 1beta-methylcarbapenems, one type having a (2S,4S)-2-[1,1-dimethyl-2-(1-piperazinyl)carbonyl]pyrrolidinio-4-+ ++ylthio group and the other type having a (2S,4S)-2-(4-carbamoylmethyl-4-methylhomopiperazinio-1-yl carbonyl)pyrrolidin-4-ylthio group, show potent and well balanced antibacterial activity as well as high stability against dehydropeptidase-I. The in vivo potency of these two carbapenems was compared with that of meropenem. The structure-activity relationships leading to these carbapenems are also described.

Animals↗

Comparison of technetium-99m-MIBI, technetium-99m-tetrofosmin, ultrasound and MRI for localization of abnormal parathyroid glands.

UNLABELLED: Abnormal parathyroid tissue can be identified by radionuclide imaging with either 99mTc-MIBI or 99mTc-tetrofosmin. This study compared the relative sensitivity of these two agents to localize parathyroid hyperplasia and adenoma. METHODS: Twenty patients with primary (n = 9) or secondary (n = 11) hyperparathyroidism were studied with 99mTc-MIBI and 99mTc-tetrofosmin parathyroid imaging, ultrasonography and MRI. Radionuclide images of the neck were acquired 10 min and 2-3 hr after radiopharmaceutical injection. The images were visually evaluated for abnormal focal areas of increased tracer localization in the neck and mediastinum. A parathyroid gland/normal thyroid tissue activity ratio (referred to as the P/T uptake ratio) was calculated for each positive scan. RESULTS: Of the 46 parathyroid glands surgically explored, the overall sensitivity and specificity of MIBI imaging were 83% and 83% (38/46); tetrofosmin imaging 87% and 83% (40/46); ultrasonography 78% and 40% (36/46); and MRI 80% and 60% (37/46), respectively. Both radiopharmaceuticals performed well in the nine patients found to have adenoma. The sensitivity and specificity of MIBI imaging were 100% and 100% (9/9); tetrofosmin imaging 100% and 100% (9/9); ultrasonography 78% and 67% (7/9); and MRI 100% and 100% (9/9), respectively. In the 37 glands with hyperplasia, MIBI imaging had a sensitivity of 78% and specificity of 75%; tetrofosmin imaging 84% and 75%; ultrasonography 78% and 43%; and MRI 73% and 60%, respectively. CONCLUSION: All imaging techniques localized abnormal parathyroid glands. The radiotracers have equal sensitivity for the localization of abnormal parathyroid glands. The sensitivity of these tracers was high as compared to ultrasonography or MRI.

Adenoma↗