Internal photoemission spectroscopy for a PtSi/p-type Si Schottky-barrier diode.
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Journal Article↗
Biomedical subjects
Y Asano
Publications and source records attributed to Y Asano.
Activation and cytotoxicity of 2-alpha-aminoacyl prodrugs of methotrexate.
In an effort to improve the selectivity of the anticancer drug methotrexate (MTX), a series of potential prodrugs in which the 2-amino group was acylated with various alpha-amino acids (as well as L-pyroglutamic acid) was synthesized. Such derivatives are anticipated to be hydrolysed to MTX by appropriate aminopeptidases localized (over-expressed naturally or targeted as anti-tumor antibody conjugates) in the vicinity of the tumor. The L-leucyl, L-valyl, L-isoleucyl, D-alanyl and L-pyroglutamyl derivatives were assessed as to their suitability as prodrugs. Except for the L-pyroglutamyl compound, all derivatives decomposed slowly when incubated in phosphate buffer, pH 7.3; the formation of MTX was minimal. No major differences were observed when serum was included in the incubation medium, except for the L-leucyl compound, which was hydrolysed to MTX. The L-leucyl, L-valyl and L-isoleucyl derivatives were hydrolysed readily to MTX by aminopeptidase M (EC 3.4.11.2), while the L-pyroglutamyl and D-alanyl compounds were activated by pyroglutamate aminopeptidase (EC 3.4.19.3) (from Bacillus amyloliquefaciens) and D-aminopeptidase (from Ochrobactrum anthropi), respectively. When tested for inhibition of the target enzyme dihydrofolate reductase (DHFR; EC 1.5.1.3), 2-L-valyl-MTX showed inhibition two orders of magnitude poorer than that given by MTX, in agreement with the expectation that acylation of the 2-amino group reduces binding to DHFR. After treatment of this derivative with aminopeptidase M, the extent of inhibition correlated with the amount of MTX formed. MTX derivatives alone or in combination with the complementary peptidase were tested for cytotoxicity on murine L1210 cells in culture. The above-listed derivatives were considerably less cytotoxic than MTX, except for the L-leucyl derivative which showed considerable cytotoxicity. When the appropriate exogenous peptidase was included, the cytotoxicity of the activated prodrugs approached that of MTX. These results indicate that 2-L-leucyl-MTX is unsuitable as a prodrug since it is activated prematurely by serum enzymes. Although the L-valyl and L-isoleucyl derivatives do not hydrolyse to MTX in serum and are readily activated, they are not ideal prodrugs since they decompose under physiological conditions; the properties of the decomposition product will have a bearing on the ultimate suitability of these compounds. 2-L-Pyroglutamyl-MTX is the best candidate prodrug, showing stability and ready activation by the appropriate aminopeptidase.
Aminopeptidases↗
Detection of human herpesvirus 6 DNAs in samples from several body sites of patients with exanthem subitum and their mothers by polymerase chain reaction assay.
Polymerase chain reaction amplification was used to detect human herpesvirus 6 (HHV-6) DNAs in peripheral blood mononuclear cells (MNCs), plasma, saliva, stool, and urine from three patients with exanthem subitum and in peripheral blood MNCs, plasma, and saliva from their mothers. HHV-6 DNAs were detected in MNCs during and after the disease and were found in plasma only in the acute phase. The virus DNAs were also detected in saliva after recovery from the illness and were found persistently or intermittently in stool but not in urine samples after the onset of the disease. In contrast, one of the three mothers excreted HHV-6 DNAs persistently in saliva. None of the mothers had the virus DNAs in peripheral blood MNCs and plasma nor a significant increase in antibody titers to HHV-6 after possible exposure from their children. These findings suggest systemic replication of HHV-6 during the acute phase in patients with exanthem subitum and persistent infection of the virus in several organs after recovery from the disease.
Adult↗
Hyperosmolality rapidly reduces atrial-natriuretic-peptide-dependent cyclic guanosine monophosphate production in cultured rat inner medullary collecting duct cells.
The present study was undertaken to explore the acute effect of hyperosmolality on the response of cultured rat inner medullary collecting duct (IMCD) cells to atrial natriuretic peptide (ANP). In contrast to the stimulatory effect of chronic incubation (12 h) in hypertonic medium, it was found that short-term incubation (< 2 h) reversibly suppressed the ANP-dependent cyclic guanosine monophosphate (cGMP) production. Urea, NaCl and mannitol were equi-potent as the osmolyte in suppressing the ANP-dependent cGMP production. Receptor binding assay revealed that hyperosmolality induced a rapid and marked reduction of the maximum binding (Bmax) of ANP without a significant change of the dissociation constant (Kd). Pretreatment with protein kinase C inhibitors (calphostin-C, staurosporin) or with cytoskeleton modulators (cytochalasin-B, colchicine) did not affect the inhibitory effect of hyperosmolality. In conclusion, acute hypertonicity inhibited the ANP-induced cGMP production in contrast to chronic hypertonicity, and reduction of the number of ANP binding sites was considered to be a mechanism responsible for the inhibitory effect of hypertonicity.
Alkaloids↗
Role of [Ca2+]i in lethal oxidative injury in rat cultured inner medullary collecting duct cells.
Reactive oxygen metabolites have been implicated in the pathogenesis of toxic, ischaemic and immunologically mediated renal injury. An increase in the cytosolic free Ca2+ concentration ([Ca2+]i) has been proposed as a mechanism of oxidative stress-induced cell injury. We used a fluorescence spectrometer and a fluorescence probe to measure the [Ca2+]i and viability of rat primary cultured inner medullary collecting duct (IMCD) cells during oxidative stress induced by 5 mM tert-butyl hydroperoxide (TBHP). Initially, this oxidative stress evoked a small increase in [Ca2+]i which was followed by a slower sustained increase from the resting level of 170.8 +/- 38.8 nM to 1490.5 +/- 301.7 nM after 60 min, and this preceded the loss of plasma membrane integrity, measured by the propidium iodide fluorescence method. The elimination of extracellular Ca2+ from the culture medium prevented the TBHP-induced [Ca2+]i increase and improved cell viability. Restoration of extracellular Ca2+ resulted in an immediate and large increase in [Ca2+]i and extensive cell death. Verapamil, a Ca2+ channel blocker, inhibited the [Ca2+]i increase and afforded significant protection against cellular injury following exposure to TBHP-induced oxidative stress. Extracellular acidosis also prevented the increase in [Ca2+]i and cell death caused by this oxidative stress. These results are consistent with the hypothesis that oxidative stress-induced IMCD cellular injury may be the result of increased [Ca2+]i caused, in part, by activation of voltage-dependent Ca2+ channels.
Animals↗
3-Methylaspartate ammonia-lyase from a facultative anaerobe, strain YG-1002.
3-Methylaspartase was purified 24-fold and crystallized from the crude extract of the cells of a facultative anaerobic bacterium from soil, strain YG-1002. The molecular mass of the native enzyme was about 84 kDa and that of the subunit was about 42 kDa. The pH optimum for the deamination reaction of (2S, 3S)-3-methylaspartic acid and those for the amination reaction of mesaconic acid were 9.7 and 8.5; its optimum temperature was 50 degrees C. The enzyme was stable at pH 5.5-11.0 and up to 50 degrees C. The enzyme required both divalent and monovalent cations such as Mg2+ and K+. The enzyme was inhibited by sulfhydryl reagents, metal-chelating reagents and some divalent cations. The enzyme catalyzed the reversible amination/deamination reactions between several 3-substituted (S)-aspartic acids and their corresponding fumaric acid derivatives. The enzyme preferentially acted on (2S, 3S)-3-methylaspartic acid and mesaconic acid in the deamination and the amination reactions respectively. The enzyme showed high similarities in several enzymological properties and N-terminal amino acid sequence with 3-methylaspartase from an obligate anaerobic bacterium Clostridium tetanomorphum.
Amino Acid Sequence↗
Mechanisms of hyperkalemia caused by nafamostat mesilate.
1. Nafamostat mesilate (NM) is a novel serine-protease inhibitor used for the treatment of acute pancreatitis and disseminated intravascular coagulation. Recently, NM has been reported to cause hyperkalemia due to reduced urinary excretion of potassium (K). 2. This review briefly summarizes the roles of the cortical collecting duct (CCD) in the renal K excretion. 3. In vitro microperfusion technique was applied to examine whether NM, and its two metabolites, p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol, directly act on the CCD. 4. It was demonstrated that these compounds act mainly on the apical membrane of the collecting duct cell in the CCD and inhibit the amiloride-sensitive sodium (Na) conductance, resulting in an inhibition of K secretion. PGBA had the most potent action. 5. This direct action of these two metabolites, rather than NM, could contribute to the NM-induced hyperkalemia.
Animals↗
Human herpesvirus-7 (HHV-7): current status.
BACKGROUND: Human herpesvirus-7 (HHV-7) is a newly discovered virus and very little is known about its prevalence, biologic, immunologic and molecular biology aspect. Besides the HHV-7 etiologic role in a few cases of exanthem subitum, its association with other diseases has not been reported. OBJECTIVES: To review what is currently known about HHV-7. RESULTS: HHV-7 was first isolated in 1990 from purified T-cells from a healthy individual. Following this report, an independent isolation of HHV-7 was reported from the mononuclear cells (PBMC) of a chronic fatigue syndrome patient. HHV-7 is closely related to human herpesvirus-6 (HHV-6) and human cytomegalovirus (HCMV), but is distinct from Epstein-Barr virus (EBV), herpes simplex virus and varicella zoster virus. Using polyvalent and monoclonal antibodies, several HHV-7 viral proteins were identified, ranging from 136 to 30 kDa. HHV-7 infection occurs later than HHV-6, which appears in early childhood. HHV-7 is ubiquitous, and its prevalence rate is >85% in the US population, although its rates of prevalence in Japan is lower than in the USA and Europe. HHV-7 is frequently isolated from saliva; however, HHV-7 has been consistently isolated from PBMC from young children as well. Several cases of exanthem subitum have been linked to primary infection of HHV-7, suggesting that it may also cause exanthem subitum. Primary infection with HHV-7 was also reported from a patient with features of hepatitis and exanthem subitum. This virus was also isolated from tissues from a case of hepatosplenomegaly and pancytopenia lacking either EBV or HCMV. Thus far, no other disease associated with HHV-7 has been reported. Only one continuous T-cell line (SupT1) can support the replication of HHV-7, but the virus yield is extremely low. CONCLUSIONS: It has been about 4 years since this member of the human herpesvirus family was reported. In the coming years, more data will be available on the epidemiology, biology, immunology, molecular biology, and pathogenesis of HHV-7. The finding of reciprocal interference between HHV-7 and HIV-1, suggesting competition at the receptor level is important, needs further work and here HHV-7 may play a role as a negative cofactor in the natural history of HIV infection. Because of HHV-7 interaction with HIV-1, the possibility of its vertical transmission needs to be investigated. This review on HHV-7 is intended to provide current information on HHV-7.
Journal Article↗
Diagnosis of right ventricular overload by body surface QRST isointegral maps in children with postoperative right bundle branch block.
The utility of body surface QRST isointegral maps (QRST-Imaps) for the detection of right ventricular (RV) overload was examined in children with postoperative development of right bundle branch block. In healthy children with no evidence of bundle branch block (n = 31), the QRST-Imap demonstrated a maximum at the left anterior chest and a minimum near the right shoulder with a single dipole distribution. The positive areas extended from the left anterior chest to the left back, and negative areas extended from the right anterior chest to the right back. Children with complete right bundle branch block but without heart disease demonstrated a QRST-Imap that was similar to that seen in normal children. In patients with RV overload (n = 15; 8 with ventricular septal defect and complicated anomaly and 7 with tetralogy of Fallot), the QRST-Imaps were abnormal and demonstrated double maxima, a rightward shift of the maximum, and extension of positive areas to the right chest. In the 10 patients who developed postoperative complete right bundle branch block, 4 had no evidence of RV overload by hemodynamic or echocardiographic assessment and demonstrated a normal QRST-Imap. In the six children who had residual RV overload during hemodynamic assessment, the QRST-Imap was abnormal. These results suggest that the QRST-Imap is a useful method for the detection of RV overload in pediatric patients complicated with conduction disturbances.
Adolescent↗
QRST isointegral map reflects the sudden reduction of right ventricular pressure after balloon pulmonary valvuloplasty.
To elucidate the mechanism of electrocardiographic changes due to right ventricular pressure overload, serial changes on body surface maps recorded in two children with valvular pulmonary stenosis before and after successful reduction of right ventricular pressure by balloon valvuloplasty (BVP) were studied. Body surface maps and 12-lead electrocardiograms were simultaneously recorded before and 1-1.5 hours, 8 hours, and 5 days after BVP. Before BVP, QRST isointegral maps showed either two maxima or an expanded single maximum on the right anterior chest. These abnormal characteristics become normal or near normal 1-1.5 hours after BVP. Electrocardiographic waveforms and QRS and ST-T isointegral maps showed minimal changes. Changes in QRST isointegral maps were observed near the center of the midanterior chest. These results suggest that increased right ventricular pressure caused a primary repolarization abnormality in the mid-anterior chest that was easily detected by body surface QRST isointegral maps.
Body Surface Potential Mapping↗
Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction.
A sensitive and specific polymerase chain reaction method for the detection of human herpesvirus 6 (HHV-6) DNA in serum or plasma has been developed. In total, 157 human serum or plasma samples were studied. HHV-6 DNA was detected in 6 (85.7%) of 7 children with exanthem subitum, 3 (23.1%) of 13 bone marrow transplant (BMT) recipients, 4 (22.2%) of 18 human immunodeficiency virus (HIV)-infected patients, 1 (2.6%) of 39 patients with chronic fatigue syndrome, and none of 37 healthy adults. In the HHV-6-positive BMT recipients, HHV-6 plasma DNA was transiently detected during episodes of fever and respiratory infection. In children with exanthem subitum and in 1 HIV-infected patient, the HHV-6 strains were characterized as variant B, whereas variant A was detected in all other patients. Detection of viral DNA in serum or plasma is a marker of active infection that can be used to investigate the role of HHV-6 in human disease.
Adult↗
Photoaffinity labeling of influenza virus RNA polymerase PB1 subunit with 8-azido GTP.
8-Azido GTP (8-N3 GTP) was demonstrated to be polymerized into RNA by influenza virus-associated RNA polymerase at about one tenth the rate of GTP incorporation. The Km value for the azido analogue of GTP in primer-dependent RNA synthesis was 94 microM whereas Km for the natural substrate, GTP, was 6.7 microM. Upon exposure of a mixture of 8-N3 [alpha-32P]GTP and influenza virus ribonucleoprotein (RNP) complexes to ultraviolet light, the PB1 subunit of viral RNA polymerase was selectively radio-labeled. The photo-labeling of PB1 was competed strongly by GTP and to lesser extents by other nucleoside 5'-triphosphates. These results altogether support the prediction that the substrate-binding site (S site) of influenza RNA polymerase is located on the PB1 protein. In the presence of ApG primer, the 8-N3 GTP binding was reduced to about 40% level, suggesting that the GTP analogue can bind not only to the S site but also to the primer- and product-binding site (P site).
Affinity Labels↗
Arteriovenous differences in plasma concentrations of catechols in rats with neuropathic pain.
BACKGROUND: Alterations in cutaneous temperature, sweating, and cutaneous blood flow in patients with pain states, such as reflex sympathetic dystrophy and causalgia, have been interpreted as evidence for exaggerated sympathetic outflow. It was determined whether pain behavior in a rat model of sympathetically maintained pain is associated with alterations in regional sympathoneural function. METHODS: Peripheral neuropathy was induced in 29 Sprague-Dawley rats by ligation of the left L5 and L6 spinal nerves. Sixteen other rats had sham surgery (nerve exposure without ligation). Animals were tested for behavioral signs of allodynia (decreased paw withdrawal thresholds to mechanical stimuli) at 2 and 4 weeks after the surgery. Arterial and iliac venous blood samples (left, affected; right, control) were obtained at 2 weeks (NP2, n = 14) and 4 weeks (NP4, n = 15) after neuropathic or sham (n = 8 at 2 and 4 weeks) surgery. Plasma concentrations of dihydroxyphenylalanine, dihydroxyphenylacetic acid, dopamine, norepinephrine, and the intraneuronal norepinephrine metabolite, 3,4-dihydroxyphenylglycol, were analyzed in arterial and left and right iliac venous samples. RESULTS: A decrease in paw withdrawal threshold was observed in neuropathic (NP2 and NP4) but not sham-operated rats. Affected and control limbs did not differ in arteriovenous differences in concentrations of dihydroxyphenylalanine, dihydroxyphenylacetic acid, dopamine, or 3,4-dihydroxyphenylglycol. No differences were observed between sham-operated and neuropathic animals in these arteriovenous increments. In contrast, affected limbs of NP2 rats had a reduced arteriovenous increment in norepinephrine concentrations, compared to that in the control side (P < 0.05). CONCLUSIONS: No neurochemical evidence of sympathetic hyperactivity is observed in the rat model of neuropathic pain; if anything, norepinephrine release is decreased in the affected limb. Autonomic disturbances in neuropathic pain are therefore more likely the result of receptor supersensitivity than increased local sympathoneural traffic.
Animals↗
Enterovirus infections in children.
International cooperation and widespread use of trivalent oral poliovaccine has almost eliminated paralytic poliomyelitis from developed countries and is now dramatically decreasing the disease in developing countries. The remarkable results are based on the strategies recommended by the World Health Organization, which include national mass campaigns for administering oral polio vaccine to all children younger than 5 years of age, enhanced surveillance to find patients with acute flaccid paralysis, creating a network of laboratories for viral diagnosis, and targeted immunization to populations in endemic areas. Another remarkable advance in clinical and research fields of enterovirus infections is the development of molecular genetic technologies such as polymerase chain reaction and in situ hybridization assays. A cloned enterovirus complementary DNA prepared from the highly conserved 5' region of the enterovirus genome can be used for rapid and sensitive group-specific diagnosis of enterovirus infections. This complementary DNA is currently being used to study the molecular mechanisms in the pathogenesis of enteroviral heart disease; lesions in acute and chronic myocarditis and even in end-stage dilated cardiomyopathy may be associated with replication of enteroviruses.
Central Nervous System Diseases↗
Role of GTPase activity of murine Mx1 protein in nuclear localization and anti-influenza virus activity.
Murine Mx1 protein is an interferon-inducible GTPase which localizes in nuclei and inhibits influenza virus infection. Wild-type Mx1 and two mutant Mx1 proteins, each carrying a single mutation either in the GTP-binding motif (S50I) or in the self-assembly motif (C71S), were expressed in MDCK cells. Wild-type Mx1 localized in nuclei, forming small granules with minute dots, and inhibited influenza virus growth. Mutant S50I, which had no GTP-binding or GTPase activities, formed linear structures in nuclei and lacked anti-viral activity, while C71S appeared diffuse in nuclei as minute dots without granules, but retained the inhibitory activity against influenza virus growth. A correlation existed between GTPase activity, intranuclear distribution and antiviral activity. We concluded that GTPase activity is essential for expression of the biological activity of Mx1 protein.
Animals↗
Compton scattering of 20- to 40-keV photons.
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Journal Article↗
The inferior vena cava diameter as a marker of dry weight in chronic hemodialyzed patients.
We have previously reported that the diameter of the inferior vena cava (IVC) reflects the amount of body fluid in hemodialyzed (HD) patients. The present study was undertaken to depict the criteria of IVC diameters for determining dry weight (DW) in anuric HD patients. In healthy subjects, the maximal diameters during quiet expiration (IVCe) and the minimal diameters during quiet inspiration (IVCi) were 16.7 +/- 3.2 and 5.7 +/- 5.4 mm, respectively (mean +/- SD). The collapsibility index (CI, 1 - IVCi/IVCe), which inversely correlates with the central venous pressure, was 0.68 +/- 0.29. In anuric HD patients, the IVCe/CI values before and after HD were 14.9 +/- 3.2/0.68 +/- 0.24 and 8.2 +/- 2.3/0.94 +/- 0.09, respectively. IVCe decreased proportionally to the amount of ultrafiltration. In HD patients with hypervolemic pulmonary edema, the IVCe and CI values were 22.4 +/- 2.9 and 0.22 +/- 0.11, respectively. We proposed that IVCe/CI after HD is 8 +/- 3 mm/0.9 +/- 0.1 as the markers of DW in anuric HD patients and that an IVCe value > or = 22 mm together with a CI < or = 0.22 implies the warning level of body fluid retention.
Analysis of Variance↗
Electrophysiologic determinants of ventricular rate in human atrial fibrillation.
INTRODUCTION: The mechanisms of the ventricular response during atrial fibrillation (AF) remain uncertain. The parameters obtained during an electrophysiologic study, including atrial rates during AF, were analyzed to clarify further the determinants of the ventricular rate during AF. METHODS AND RESULTS: Thirty patients without manifest preexcitation in whom AF was induced during electrophysiologic study were divided into two groups. Group 1 consisted of 20 patients (ages 55 +/- 10 years) without a dual AV nodal pathway. Group 2 consisted of 10 patients (ages 53 +/- 13 years) having a dual AV nodal pathway. The correlation coefficient between the mean RR interval during AF (mRR) and the mean intra-atrial potential interval during AF (mff) was positive (0.05 [P < 0.05] in group 1 and 0.37 [P = NS] in group 2). The correlation coefficient of the mRR against the functional refractory periods of the AV node (AVFRP) was 0.73 (P < 0.001) in group 1. The correlation coefficients between mRR and the fast AV nodal pathway functional refractory periods and the slow AV nodal pathway effective refractory periods (SPERP) were 0.58 (P = NS) and 0.7 (P < 0.05) in group 2, respectively. The correlation coefficients between mRR against (mff x AVFRP)1/2 in group 1 and (mff x SPERP)1/2 in group 2 were 0.8 (P < 0.001) and 0.72 (P < 0.05), respectively. CONCLUSIONS: This clinical study did not indicate an inverse relation between the atrial and ventricular rates that had been reported by the previous experimental study. The ventricular rate during AF appeared to be quantitatively related to the atrial rate via AV node function. The importance of the slow pathway in determining the ventricular rate during AF was observed.
Aged↗