Three stress fractures at different sites in the same tibia--a case report.
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Casts, Surgical↗
Biomedical subjects
K Nagata
Publications and source records attributed to K Nagata.
[Understanding of informed consent by elderly patients].
Fifty patients, aged 60 years or more, who had been admitted to a hematology ward for more than 1 month, were studied in regard to their understanding of informed consent. The doctors informed 74% of their patients about the disease for which they were being treated. The rate of informing patients remained low in those with advanced age or with malignant tumors. However, only 42% of the patients realized that they had been informed of their diagnosis and clinical condition. The comprehension rate remained low at 43.2% even in patients who were informed by their doctors. While 60% of patients declared that they understood what the doctors described, only 36% could write something about the name or the state of their disease. Even among the patients who could understand the doctor's explanation, the comprehension rate was 43.3%. Sixty-six percent of patients demonstrated their wish to have a correct explanation of their diagnosis, 36% of patients wanted to be treated according to their own wishes, and 48% of patients left the decisions regarding their treatment to the doctors.
Aged↗
[Complete remission of essential thrombocythemia after recovery from severe bone marrow aplasia induced by busulfan treatment].
A 63-year-old woman was found to have thrombocythemia and was referred to our hospital for further evaluation in September 1990. Peripheral blood showed platelet 170.0 x 10(4)/microliter, WBC 14,900/microliter and Hb 9.8 g/dl. Bone marrow was hypercellular with increased megakaryocytes and normal karyotype. She was diagnosed as essential thrombocythemia (ET), and treated with 2 mg of busulfan daily for 3 months until her platelet count decreased to 33.1 x 10(4)/microliter. Busulfan was given again for 40 days (a total of 80 mg) in another hospital when the platelet count increased to 71.1 x 10(4)/microliter in September 1991. In December 1991, she was admitted to our hospital because of pancytopenia. Examination of blood revealed platelet 0.4 x 10(4)/microliter, WBC 1,800/microliter and Hb 7.0 g/dl with hypocellular marrow. A diagnosis of busulfan-induced severe bone marrow aplasia was made. We administered metenolone acetate 15 mg and G-CSF 300 micrograms daily. Blood transfusions were given frequently. However, no effect was observed during her hospitalization. After discharge, G-CSF 600 micrograms and erythropoietin 24,000 units were continued twice a week in combination with metanolone acetate. Pancytopenia gradually began to improve as of June 1992, and then trilineage recovery was achieved in March 1994 with platelet 13.3 x 10(4)/microliter, WBC 5,500/microliter and Hb 12.1 g/dl. The platelet count has been within the normal range for more than 2 years after recovery.
Anemia, Aplastic↗
Dexamethasone and nitric oxide synthase gene expression in brain.
Systemic administration of lipopolysaccharide (LPS), which causes endotoxemia and systemic inflammation, has been reported to induce expression of the gene for type II inducible nitric oxide synthase (iNOS) in peripheral organs. This study was carried out to examine whether intraperitoneally injected LPS elicits the expression of iNOS messenger ribonucleic acid (mRNA) in the rat brain. We also investigated whether intraperitoneal treatment with dexamethasone (DEX) prevents this induction. To determine levels of iNOS mRNA, a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method was employed. Treatment with LPS induced the expression of iNOS mRNA in various brain regions, accounting for approximately 1 x 10(5) to 4 x 10(5) molecules per micrograms of poly A+ RNA, and these inductions were markedly suppressed by DEX. The results suggest that, during systemic inflammation, iNOS mRNA induction occurs in brain through a DEX-sensitive mechanism.
Animals↗
Effect of vesnarinone, a quinolinone derivative, on the growth of leukemic blasts in acute myelogenous leukemia.
We studied the effects of vesnarinone, a quinolinone derivative used clinically for the treatment of chronic congestive heart failure, on the leukemic blast progenitors in acute myelogenous leukemia (AML) patients and on the normal hematopoietic precursors, colony-forming unit in culture (CFU-C), and colony-forming unit erythroid (CFU-E). Leukemic blast progenitors made blast colonies in the presence of granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), or interleukin-3 (IL-3). Blast colony-formation was suppressed by vesnarinone in a dose-responsive manner regardless of growth factor added. Vesnarinone suppressed the primary (PE1) and secondary (PE2) colony-formation of leukemic blast progenitors in six AML patients tested. The suppression by vesnarinone did not significantly differ between PE1 and PE2. This finding suggests that vesnarinone exerts an almost equivalent effects on the terminal divisions and the self-renewal of leukemic blast progenitors. Furthermore, this drug suppressed the growth of clonogenic cells of five AML cell lines, OCI/AML1a, OCI/AML2, OCI/AML3, OCI/AML5, and OCI/AML6. Normal hematopoietic precursors CFU-C and CFU-E were also suppressed by vesnarinone, although vesnarinone was less toxic to normal hematopoietic than to leukemic blast progenitors. The possible usefulness of vesnarinone as a new approach to the treatment of AML patients is discussed.
Adult↗
Differential expression of low Mr GTP-binding proteins in human megakaryoblastic leukemia cell line, MEG-01, and their possible involvement in the differentiation process.
The expression of various low Mr GTP-binding proteins at various states of differentiation of a human megakaryoblastic leukemia cell line, MEG-01, was analyzed using thermocycle amplification of mRNA and immunoblotting. MEG-01 cells were found to express mRNAs of rap1A, rap1B, rap2B, ralA, rhoA, rac1, rac2, CDC42Hs, rab1, rab3B, rab6, ram and ran, but not rab4, and the proteins of Rap1, Rap2, RhoA, Rac1, Rac2, Rab3B, Rab4, Rab6 and Rab8 were expressed. Differentiation of MEG-01 cells induced by 100 nM 12-O-tetradecanoylphorbol-13-acetate revealed the considerable increases in mRNA expression of rap1B, rab3B, rab4, ram and ran whereas the levels of rap2B, rhoA and rac1 decreased. During the differentiation process, significant changes in protein levels of Rap1, RhoA, Rac1, Rac2, Rab3B, Rab4 and Rab6 were observed among three subcellular (cytosol, Triton X-100-soluble membrane and -insoluble cytoskeleton) fractions. The present investigation may be useful for the study of the megakaryocyte differentiation.
Blood Platelets↗
Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels.
The effects of riluzole, a neuroprotective drug, on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion neurons were studied using the whole-cell patch clamp technique. At the resting potential, riluzole preferentially blocked TTX-S sodium channels, whereas at more negative potentials, it blocked both types of sodium channels almost equally. The apparent dissociation constants for riluzole to block TTX-S and TTX-R sodium channels in their resting state were 90 and 143 microM, respectively. Riluzole shifted the voltage dependence of activation of TTX-R sodium channels in the depolarizing direction more than that of TTX-S sodium channels. The voltage dependence of the fast inactivation of both types of sodium channels was shifted in the hyperpolarizing direction in a dose-dependent manner, and the apparent dissociation constants for riluzole to block the inactivated channels were estimated to be 2 and 3 microM for the TTX-S and TTX-R sodium channels, respectively, indicating a much higher affinity for the inactivated channels than for the resting channels. Riluzole was equally effective in blocking both types of sodium channels in their slow inactivated state. Since more TTX-S channels are inactivated than TTX-R channels at the resting potential, riluzole blocks TTX-S sodium channels more potently than TTX-R sodium channels. It was concluded that one of the mechanisms by which riluzole exerts its neuroprotective action is to preferentially block the inactivated sodium channel of damaged or depolarized neurons under ischemic conditions, thereby suppressing excess stimulation of the glutamatergic receptors and massive influx of Ca++.
Animals↗
Effects of the neuroprotective agent riluzole on the high voltage-activated calcium channels of rat dorsal root ganglion neurons.
The effects of riluzole, a neuroprotective drug, on high voltage-activated (HVA) calcium channels of rat dorsal root ganglion neurons were studied using the whole-cell patch-clamp technique. Riluzole inhibited HVA calcium channel currents in a dose-dependent, time-dependent and reversible manner. The apparent dissociation constants for riluzole inhibition of the transient and sustained components of the current were 42.6 and 39.5 microM, respectively. Riluzole accelerated the activation kinetics of calcium channels without affecting the voltage dependence of activation. It accelerated the fast component of deactivation kinetics without affecting the slow component. It also accelerated fast and slow inactivation kinetics of the HVA channels. However, only one of the two components in the steady-state inactivation curve for the HVA channels was shifted in the hyperpolarizing direction by riluzole, which indicates differential block of the multiple-type HVA channels. By use of the specific blockers nimodipine, omega-conotoxin GVIA and omega-agatoxin IVA, the HVA calcium channels were found to comprise L-type (10%), N-type (63%), P/Q-type (23%) and R-type (9%). Riluzole blocked N- and P/Q-type channels, but not L-type channel, with the order of efficacy of P/Q- > N- >> L-type channels. Riluzole inhibition of N- and P/Q-type calcium channels may result in reduced calcium influx at presynaptic terminals, which thereby decreases excessive excitatory neurotransmitter release, especially glutamate, a mechanism known to cause neuronal death in ischemic conditions.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
[The Mx protein that confers the resistance to influenza virus].
The murine Mx1 protein was identified as an interferon-inducible host factor that confers the resistance to influenza virus. Mx proteins homologous to the murine Mx1 are subsequently found in a wide variety of species including human, rat, chicken, fish and so on. Mx proteins have the typical GTP-binding motif, and in fact, are shown to be GTP-binding proteins and GTPases. Nuclear Mx proteins selectively inhibit the primary transcription of orthomyxoviruses. In contrast, the cytoplasmic Mx protein, for instance, human MxA blocks the multiplication of not only orthomyxovirus but also rhabdovirus, paramyxovirus, and bunyavirus. Although the molecular mechanism by which Mx inhibits the virus multiplication is not completely clear, Mx may exert the antiviral activity possibly by the mechanism that VPS1p or dynamin, members of the Mx family, is involved in the intracellular protein translocation.
Animals↗
TCV-116 inhibits interstitial fibrosis and HSP47 mRNA in rat obstructive nephropathy.
Unilateral ureteral obstruction (UUO) is a well established disease model leading to fibrosis of the obstructed kidney. In this model, involvement of enhanced renin-angiotensin system in the pathogenesis of interstitial fibrosis has been demonstrated. A 47-kDa heat-shock protein (HSP47) was originally identified as a collagen-binding stress protein, and is currently considered to be a collagen-specific molecular chaperone that plays a pivotal role during the biosynthesis and secretion of procollagen from endoplasmic reticulum. To test if HSP47 is involved in interstitial fibrosis in UUO, we examined the expression of HSP47 mRNA in rat UUO kidneys after 12 hours. 1, 4, 7 days of obstruction. HSP47 mRNA expression was significantly increased as early as 12 hours after obstruction and was sustained at the increased level until seven days. Type I collagen mRNA significantly increased after four days of UUO. Fibrotic changes of interstitium appeared in Masson's trichrome stained section after four days. To explore the possible involvement of angiotensin II (Ang II) in HSP47 induction, the effect of Ang II receptor antagonist (TCV-116) and angiotensin converting enzyme inhibitor (lisinopril) was tested. TCV-116 or lisinopril was given to the animals orally once a day at the dose of 10 mg/kg. TCV-116 or lisinopril significantly ameliorated the fibrotic change of interstitium seven days after obstruction. HSP47 and type I collagen mRNA levels in the TCV-116- or lisinopril-treated groups were reduced to about 60% of untreated UUO. A possible involvement of HSP47 in the pathogenesis of interstitial fibrosis in UUO is suggested; however, further investigation is required to identify the signals involved in the induction of HSP47 in UUO.
Angiotensin II↗
Dynamic exercise-induced changes in diastolic properties of the regional myocardium in hypertensive left ventricular hypertrophy.
We investigated the effect of mild exercise on global and regional diastolic function in patients with hypertensive left ventricular hypertrophy (LVH), using simultaneous measurement of micromanometric left ventricular pressure and echocardiographic indexes. Although left ventricular end-diastolic pressure (LVEDP) at rest in the hypertensive LVH group was similar to that in the control normotensive group, who had no abnormality on echocardiography or cardiac catheterization, LVEDP showed a marked increase during exercise only in the hypertensive LVH group. The pressure-dimension relation was shifted upward during exercise in all patients with hypertensive LVH. We utilized a new index of regional diastolic myocardial stiffness, KDM, which is derived from the diastolic relation between the mean wall stress and the natural logarithm of the reciprocal of wall thickness. Although KDM at rest was similar in the two groups, KDM increased significantly during exercise, both in the septum and posterior wall in patients with hypertensive LVH. The present results imply that even low-grade exercise may have deleterious effects on regional myocardial performance in patients with hypertensive LVH.
Diastole↗
[Hippocampal hypoperfusion underlying dementia due to chronic toluene intoxication].
To elucidate the pathophysiology underlying the dementia due to chronic intoxication of toluene, a positron emission tomography was carried out in a 24-year-old right-handed man who had been sniffing thinner which contains toluene for 6 years. In addition to the cerebellar ataxia and pyramidal signs, this patient exhibited a mental deterioration including recent memory disturbance: verbal IQ was 52, performance IQ was 52 and total score was 51 on WAIS-R. MRI revealed a mild diffuse cortical atrophy, symmetrical hyperintensity lesions in the corticospinal tracts including corona radiata posterior limb of the internal capsule and ventral part of the pons, and hypointensity lesions in the both thalami on T2-weighted images, whereas the changes in the deep white matter was relatively mild on T2-weighted images. In PET, both cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were diffusely decreased bilaterally, and specifically in both hippocampi, they were reduced as low as 61% of the normal values as obtained from 12 young normal volunteers. Additionally, in the frontal cortex, CBF and CMRO2 were 60% and 71% of the normal values, respectively. Although the dementia due to chronic toluene intoxication has been assumed to be closely related to the degree of the cerebral white matter lesions based on the MR findings, the present results suggest that the mental deterioration including recent memory disturbance seen in the early stage of chronic toluene intoxication is associated with the hypoperfusion and hypometabolism in the hippocampus and frontal limbic system.
Adult↗
Molecular cloning and characterization of a transcription factor for the C-type natriuretic peptide gene promoter.
Our previous studies on the promoter function of the human C-type natriuretic peptide (CNP) gene revealed the existence of two GC-rich cis elements essential for gene transcription in rat pituitary-derived GH3 cells. To isolate transcription factors that bind to those GC-rich elements, we screened a lambda ZAP cDNA library derived from GH3 cells by Southwestern screening. Several positive clones with specific binding abilities were obtained, and one was identical as TSC-22, a speculated transcriptional modulator stimulated by transforming growth factor beta (TGF-beta) of unknown function. TSC-22 significantly enhanced CNP promoter activity in GH3 cells. We further cloned a 1.8-kb full-length human TSC-22 cDNA from a fetal kidney cDNA library by a combination of polymerase chain reaction and the rapid amplification of the cDNA ends technique. In adults, human TSC-22 mRNA was highly expressed in brain, lung and heart. TSC-22 gene expression in GH3 and human aortic endothelial cells was stimulated by cytokines including TGF-beta, in correlation with the CNP mRNA increase. These results suggest that TSC-22 is a transcriptional regulator of the CNP gene and transmits signals from cytokines, such as TGF-beta, to CNP gene expression.
Adult↗
Intramedullary gadolinium-DTPA enhancement in a patient with cervical spondylotic myelopathy and an associated vascular lesion. Case report.
Intramedullary enhancement of the cervical spinal cord is rare in chronic compression disease. An accompanying vascular lesion should be considered in such a case. A 59-year-old man presented with severe cervical spondylotic myelopathy. Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging showed intramedullary enhancement at the C5-6 level, which was the most severely compressed level. A right ascending cervical arteriogram demonstrated a spinal arteriovenous fistula (AVF) fed mainly by the C-6 radicular artery and draining from the posterior medullary vein. Surgery was performed to decompress the myelopathy and to obliterate the AVF. Postoperative MR imaging with Gd-DTPA enhancement showed immediate and complete disappearance of the previous enhancement. The intramedullary enhancement presumably resulted from the intraparenchymal hemodynamics due to the AVF.
Journal Article↗
Differential block of two types of sodium channels by anticonvulsants.
The differential effects of the anticonvulsants phenytoin and carbamazepine on the sodium channels of rat dorsal root ganglion (DRG) neurons were studied using the patch clamp technique. The action potentials from tetrodotoxin-resistant (TTX-R) cells were less sensitive to phenytoin and carbamazepine than those from tetrodotoxin-sensitive (TTX-S) cells. The steady-state inactivation curve for TTX-S sodium channels was shifted by as much as 20.6 mV and 11.4 mV by phenytoin and carbamazepine at 300 microM, respectively, yet the curve for TTX-R sodium channels was shifted only by 6.0 mV and 6.9 mV, respectively. Thus, the differential action potential block of TTX-S and TTX-R cells by phenytoin and carbamazepine is due to different voltage dependence of and differential drug effects on the inactivation kinetics of two types of sodium channels.
Action Potentials↗
Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases.
Axl, Sky, and Mer, members of an Axl/Sky receptor tyrosine kinase subfamily, are typified by the cell adhesion molecule-related extracellular domain. The product of growth arrest-specific gene 6 (Gas6), structurally homologous to the anticoagulant protein S, was recently identified as the ligand for Axl and Sky, but the ligand for Mer remained unknown. We have now obtained evidence that Gas6 can also function as a ligand for Mer. Co-precipitation analysis, using soluble receptors of Axl, Sky, and Mer (Axl-Fc, Sky-Fc, and Mer-Fc) composed of the extracellular domain of receptors fused to the Fc domain of immunoglobulin G1, clearly showed that Gas6, but not protein S, specifically bound to Axl-Fc, Sky-Fc, and Mer-Fc fusion proteins. Quantitative kinetic analyses using a BIAcore biosensor instrument revealed dissociation constants (Kd) of the binding of rat Gas6 to Axl-Fc, Sky-Fc, and Mer-Fc are 0.4, 2.7, and 29 nM, respectively. We also found that Gas6 stimulated tyrosine phosphorylation of Axl, Sky, and Mer receptors ectopically expressed in Chinese hamster ovary cells. Taken together, these findings suggest that Gas6 is a common ligand for Axl, Sky, and Mer, all known members of an Axl/Sky receptor subfamily.
Animals↗
Reperfusion causes significant activation of heat shock transcription factor 1 in ischemic rat heart.
BACKGROUND: The myocardial protective role of heat shock protein (HSP) has been demonstrated, and there has been increasing interest in stress response in the heart. We examined the DNA-binding activity of heat shock transcription factor (HSF), by which the transcription of heat shock genes is mainly regulated, during heat shock or ischemia/reperfusion in isolated rat heart. METHODS AND RESULTS: Rat hearts were isolated and perfused with Krebs-Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element, which is present upstream of all heat shock genes. Induction of mRNAs for HSP70, HSP90, and GRP78 (glucose-regulated protein) was examined by Northern blot analysis. Although the activation of HSF during global ischemia was weak and rapidly attenuated, postischemic reperfusion induced a significant activation of HSF. In addition, although HSP70 mRNA was hardly induced during ischemia, its burst induction was detected during postischemic reperfusion. Supershift assays using specific antisera for HSF1 and HSF2 revealed that ischemia/reperfusion as well as heat shock induced the activation of HSF1 in hearts. Although the expression of HSP70 mRNA during heat shock was more vigorous than the expression during ischemia/reperfusion, the induction of HSP90 mRNA in postischemic reperfusion was significantly greater than that in heat shock. CONCLUSIONS: Our findings demonstrated that reperfusion causes a significant activation of HSF1 in ischemia-reperfused heart. The striking contrast between the induction of HSP70 mRNA and that of HSP90 mRNA suggests the presence of regulatory mechanisms other than HSF.
Animals↗