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Accidental transmission of contagious pathogens, especially hepatitis C virus (HCV), by needlestick or other means as an occupational hazard for medical staff is of concern. We retrospectively analysed cases of work-related accidental injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human immunodeficiency virus (HIV) reported to the centres for disease control at 15 hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an incidence of 0.2-3.5 accidents per month per hospital. Such accidents occurred in 297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians, four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one secretary and two others. There were 323 (77.6%) injuries caused by needlestick, 42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood splatters from patients into the eyes or mouth, 10 (2.4%) from contact with injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four cases (1.6%) of HCV infection were found and treated with one or two courses of interferon therapy, and HCV was subsequently cleared. All four patients were cured with interferon therapy. None of the HBV-injured cases resulted in infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine. No HIV or syphilis infection was contracted. In summary, chronic HCV infection acquired as an occupational hazard can be cured by appropriate treatment, such as with interferon, after early detection of the infection.

We evaluated the characteristics of the protein kinase C (PKC)-independent mechanism for ATP release in platelet-rich plasma. When ADP (10 μM) and U46619 (1 μM) were both added as agonists, a significant release was observed immediately after stimulation. The PKC inhibitor, Ro-31-7549 (10 μM), or a cyclooxygenase inhibitor, aspirin (400 μM) or indomethacin (20 μM), partially inhibited ATP release with little effect on platelet aggregation. The ATP release observed in the presence of Ro-31-7549 was abolished by a cyclooxygenase inhibitor or by preventing aggregation without stirring. In the nonstirred condition, thromboxane B 2 formation was reduced by 93%. When sodium arachidonate (1 mM) rather than U46619 was used with ADP, ATP release in the presence of Ro-31-7549 was abolished by stopping the stirring with no effect on thromboxane B 2 formation. In contrast, ADP/U46619-induced ATP release observed in the presence of aspirin was only partially inhibited when the stirring was stopped. This release was also inhibited dose-dependentl by Ro-31-7549 at concentrations between 1 and 10 μM. These results suggest that PKC-independent ATP-release in this system requires aggregation and is inhibited by a cyclooxygenase inhibitor, while PKC-dependent exocytosis is insensitive to aggregation and a cyclooxygenase inhibitor. © 1997 Elsevier Science Ltd

The plasma low density lipoprotein (LDL) of an apolipoprotein (apo) E-deficient patient was reported to contain apoB-48 (D. Kurosaka et al., Atherosclerosis 1988;88:15), which is a structural protein of chylomicrons and is not present in the fasting plasma LDL of normal subjects. We separated the LDLs containing apoB-48 (apoB-48 LDL) and apoB-100 (apoB-100 LDL) from the plasma of this patient using heparin-sepharose column chromatography. The apoB-48 LDL contained apoA-I, apoA-IV, and apoCs besides apoB-48. There were no differences in size and lipid composition of the apoB-48 and the apoB-100 LDLs, both of which contained more triglyceride than LDL from normal subjects. After incubation with apoE, the apoB-48 LDL contained twice the amount of apoE than the apoB-100 LDL and showed a marked decrease in apoA-I and apoA-IV content. These results suggest that lipoproteins containing apoB-48 in normal subjects can be quickly taken up through an apoE-mediated receptor mechanism after receiving apoE in exchange for apoA-I and A-IV.

This study investigated the postmortem diffusion of tracheal lidocaine into the blood after intubation in three individuals whose heart beat was not restored by cardiopulmonary resuscitation. The results are compared with those obtained in animal experiments using rabbits. The first human subject was a 3.5-month-old female baby who died of sudden infant death syndrome. She was autopsied approximately 20 h after death. A toxicological examination revealed the presence of 0.349 mg/L and 0.102 mg/L of lidocaine in the blood in the left and right ventricles of the heart, respectively. No lidocaine was detected in the cerebrum, liver, or right femoral muscle. The second subject was a 44-year-old man who died of brain swelling due to head injuries, and was autopsied approximately 20 h after death. Lidocaine concentrations in the hili of the left and right lungs were 10.9 mg/kg and 2.65 mg/kg, respectively, and 1.02 mg/L and 0.209 mg/L in the blood in the left and right ventricles of the heart, respectively. The right femoral vein blood contained only a trace amount of lidocaine; no lidocaine was detected in the cerebrum, liver, or right femoral muscle of this subject. The third subject was a 38-year-old man who died of bleeding due to a stab wound to the left thigh, and was autopsied approximately 20 h after death. Lidocaine concentrations were 1.41 mg/kg and 1.37 mg/kg in the hili of the left and right lungs, respectively, and 0.642 mg/L and 0.746 mg/L in the blood in the thoracic aorta and superior vena cava, respectively. No lidocaine was detected in the right femoral vein blood, cerebrum, liver or right femoral muscle. In the animal experiments, rabbits carcasses were left in the supine position at an ambient temperature following application of 1 mg/kg lidocaine hydrochloride into the trachea just above the bifurcation. Lidocaine concentrations of 0.550-4.03 mg/L and 3.05-7.30 mg/L were detected in the heart blood, one and three days after the lidocaine treatment, respectively; neither the cerebrum nor right femoral muscle contained detectable amounts of lidocaine. The pH values of body fluids and tissues of the human and animal corpses were below 7.0. This study has demonstrated that following intubation, tracheal lidocaine diffuses into surrounding fluids and tissues, and that this is attributable to postmortem acidosis. We suggest that, in subjects who underwent cardiopulmonary resuscitation with intra-tracheal intubation, heart blood and femoral vein blood should be analyzed for lidocaine. In addition, the pattern of distribution of lidocaine in the surrounding tissues may provide some information on the state of victims during cardiopulmonary resuscitation.

A calorimeter for measuring the temperature dependence of specific heat in pulsed magnetic fields is described. An Au0.16Ge0.84?thin-film thermometer and a Ni50Cr50?film heater are employed to obtain the rapid thermal response necessary for the pulsed magnetic-field experiments. The apparatus has been tested in pulsed magnetic fields up to 56.2 T (?0.3 T) and in the low temperature range from 3 to 20?K. To demonstrate the validity of the technique, measurements have been performed on single crystal samples of SiO2?and Cu3Mo2O9.

In a previous study, we characterized prostanoid and thrombin receptors expressed on a megakaryoblastic cell line, MEG-01s (Blood 78, 2328–2336, 1991). In this study, we examines the mechanism of cross-talk between intracellular Ca 2+ ([Ca 2+ ] i ) and cAMP signalings through prostanoid and thrombin receptors. Addition of a thromboxane (TX)A 2 mimetic (U46619 or STA 2 ) or thrombin stimulated the formation of inositol phosphates and dose-dependently augmented a prostaglandin (PG)I 2 mimetic (iloprost)- or forskolin-induced cAMP formation. 12- O -tetradecanoylphorbol-13-acetate (TPA) and ionomycin, to lesser extent, also augmented iloprost-induced cAMP formation. The enhancing effect of U46619 or TPA on cAMP formation was inhibited by prolonged pretreatment of the cells with TPA (2.5 μM, 24h), but not with calmodulin-antagonists; W-7, W-5, or KN-62. The elevation of [Ca 2+ ] i induced by thrombin, STA 2 or PGE 2 was significantly suppressed by pretreatment of the cells with TPA (100 nM) as well as cAMP mimetics such as dibutyryl cAMP (5 mM), forskolin (5 μM) and iloprost (1 μM). These results suggest the key role of PKC on the cross-talk between [Ca 2+ ] i and cAMP signalings through prostanoid and thrombin receptors; PKC, which is activated with TXA 2 , or thrombin, concomitantly suppress further [Ca 2+ ] i elevation and enhances the PGI 2 receptor-mediated cAMP formation, which, in turn, suppress [Ca 2+ ] i elevation.

A protein kinase inhibitor K252a suppressed the growth of HuH7 hepatoma cells and the hyperphosphorylation of retinoblastoma protein (pRb) at late G 1 phase of cell cycle. However, K252a treatment did not alter the levels of cyclin D1, cyclin E, cyclin A and Cdk2 protein bound to cyclin E or cyclin A. Therefore, the K252a inhibition of pRb phosphorylation is considered to be brought about probably by inhibiting the action of Cdk-cyclin complex rather than by changing its cellular level. These results also suggest that K252a is a useful tool for investigating the mechanism of phosphorylation of pRb mediated by Cdk-cyclin.

Cocaine and cocaethylene concentrations in blood and tissues at early stages postmortem (0-6 h) were investigated using alcohol-treated rats. Gas chromatography/mass spectrometry following a liquid/liquid extraction procedure was employed to detect these drugs. Calibration curves showed good linearity in the range of 0 to 2,500 ng/mL with correlation coefficients of 0.9999 and 0.9998 for cocaine and cocaethylene, respectively. In a group treated with cocaine and ethanol orally, the liver lost over 25% of the cocaine present at death after 1 h. Conversely, the hepatic cocaethylene concentrations at this time reached more than twice those at death. Thereafter, the hepatic concentrations of cocaine and cocaethylene were maintained at a constant level until 6 h postmortem. Similar results were obtained with rats given cocaine intramuscularly. No changes in the cocaine and cocaethylene concentrations in any other tissues during the 6-h of postmortem period were observed. The forensic pathologist and toxicologist should be aware of these phenomena when selecting postmortem specimens for the analysis of cocaine and cocaethylene and take them into account when interpreting the results.

The effects of cocaine administration route on the formation of cocaethylene, an active metabolite of cocaine produced in the presence of ethanol, were investigated using rats. When 20 mg/kg cocaine was administered into the stomach together with 2 g/kg ethanol, maximum liver concentrations of cocaine and cocaethylene, 8410 +/- 3600 and 1680 +/- 520 ng/g, respectively, were observed at 15 min. In other tissues the maximum levels of both the substances were attained in 30 min, but were much lower than those in the liver. Intramuscular administration of 20 mg/kg cocaine with 2 g/kg oral ethanol gave levels of liver cocaine as low as 103 +/- 29 to 150 +/- 35 ng/g, resulting in no detection of liver cocaethylene over the entire 180-min study period, although gradual accumulation of cocaethylene was observed in other tissues. The accumulation patterns of cocaine and cocaethylene in blood of alcohol-intoxicated rats after the i.m. administration of cocaine were similar to those in blood of drinkers after nasal insufflation of cocaine. Despite i.v. administration of 1 mg/kg cocaine with 2 g/kg oral ethanol, no detectable amounts of cocaethylene appeared in any tissues over the entire 60-min study period. The present findings are considered to be of importance in the fields of forensic and clinical toxicology for clarifying (1) the rate of in vivo cocaethylene formation and (2) the distribution of cocaine and cocaethylene in blood and tissues.

A major cytokinin found in coconut milk was isolated by using the tobacco callus growth-promoting assay as a guide during purification. The structure of the factor was determined to be 14-O-(3-O-[beta-D-galactopyranosyl-(1--2)-alpha-D-galactopyranosyl-(1--3)- alpha-L-arabinofuranosyl]-4-O-(alpha-L-arabinofuranosyl)-beta-D- galactopyranosyl)-trans-zeatin riboside [G3A2-ZR] by various NMR techniques, including heteronuclear multiple bond connectivity by 2D multiple quantum NMR (HMBC), as well as mass spectroscopy and sugar analysis. The optimum concentration of G3A2-ZR for cytokinin activity in the tobacco callus assay was estimated to be 5 x 10(-6) M, so that G3A2-ZR is one order of magnitude more potent than 1,3-diphenylurea and one order less potent than zeatin riboside. At least 20% of the cytokinin activity of coconut milk could be attributed to G3A2-ZR.

OBJECTIVE To evaluate whether there is any change in HbA1c with age and to determine the effects of body mass index (BMI), exercise, and family history of diabetes on this change. RESEARCH DESIGN AND METHODS A cross-sectional survey of 7,664 male Japanese workers aged 20–59 years was performed. All subjects received a physical examination that included measurement of HbA1c as an indicator of plasma glucose level. The subjects were classified according to their ages and BMIs, and any relationship with HbA1c levels was evaluated. Information on physical activity and family history of diabetes was obtained by a questionnaire. RESULTS In all BMI groups, HbA1c increased with age. The greatest increase in HbA1c was observed in the 40- to 49-year-old age-group in subjects with a BMI ≤26 kg/m2 and in the 30- to 39-year-old age-group in subjects with a BMI >26. HbA1c in the subjects aged 20–29 years did not change with BMI. In contrast, HbA1c in subjects aged 30–59 years was significantly higher in those with a BMI >26 when compared with those with BMI ≤20. The age-dependent increase in HbA1c was greater in subjects with a positive rather than negative family history of diabetes. This age-dependent increase was not affected by active participation in sporting activities of mild to moderate intensity for 3 or more days per week. CONCLUSIONS The age-dependent increase in HbA1c may be a consequence of the aging process itself. Furthermore, both BMI and a hereditary predisposition to diabetes, but not active participation in sports, affect this age-dependent increase in HbA1c.

Phosphatidylinositol 3-kinase (PI3-kinase) has been implicated in the regulation of vesicular transport. We examined the roles of PI3-kinase in the glucose-induced insulin secretion from the pancreatic β cell line MIN6 by using wortmannin, a potent inhibitor of PI3-kinase. Low concentrations of wortmannin markedly potentiated the glucose-induced insulin secretion. This effect was probably mediated by PI3-kinase inhibition. Furthermore, wortmannin completely canceled the suppressive effect of insulin-like growth factor-I on insulin secretion from MIN6 cells. On the basis of these results, we discuss a possible role of PI3-kinase in the negative feed-back regulation of insulin secretion.

Children with trauma visit frequently the department of oral and maxillofacial surgery. The treatment for injured permanent teeth is different from that for injured deciduous teeth. We have experienced a case of a 9-year-old boy with an injured unerupted immature permanent tooth with tooth crown fracture. When the tooth erupted gradually, fractured pieces were removed three times, and indirect pulp capping was performed. Three years after the injury eruption was almost completed and pulp was alive, even though the dental roentgenograph showed obliteration of the crown pulp cavity.

The genus Aenictus is a diverse group of army ants in the Old World tropics and subtropics. The worker-based Aenictus piercei species group of Jaitrong and Yamane (2011) is redefined and renamed here as the Aenictus minutulus group. Aenictus piercei Wheeler et Chapman, 1930 and A. lifuiae Terayama, 1984 are removed from this group; the former is moved to the A. javanus group and the latter to the A. ceylonicus group. The Southeast Asian species of the group are revised to include six species: Aenictus changmaianus Terayama et Kubota, 1993, Aenictus sp.56 of WJT, A. minimus sp. nov., A. minutulus Terayama et Yamane, 1989, A. peguensis Emery, 1895 and A. subterraneus sp. nov. Aenictus changmaianus, A. minimus and A. peguensis are probably restricted to the seasonal forest located northward from the Isthmus of Kra, while A. minutulus, A. subterraneus and Aenictus sp.56 of WJT are obviously Sundaland species inhabiting the perhumid evergreen rainforest.

We examined the roles of myosin light-chain kinase in platelet responses to ADP using wortmannin, which almost completely inhibited myosin light-chain kinase at 3-6 microM. This concentration of wortmannin did not affect ADP-induced changes in the shape of the platelets, but it markedly inhibited aggregation in platelet-rich plasma and washed platelets. ML-9, another inhibitor of myosin light chain kinase, elicited similar effects on the platelet responses to wortmannin. Electron microscopic studies showed that there was no wortmannin effect on the ADP-induced spheration of discoid platelets, pseudopod formation, or granule centralization. Wortmannin at concentrations which prevented myosin light-chain kinase also inhibited platelet aggregation induced by ADP in the presence of U46619, an analogue of thromboxane A2, which is a prerequisite for ADP-induced irreversible aggregation. Although wortmannin partially inhibited protein kinase C, the protein kinase C inhibitor Ro-31-7549 (5 microM) prevented neither ADP- or ADP/U46619-induced changes in the shape of the platelets nor aggregation. These results suggest that myosin light-chain kinase activation is a prerequisite for ADP-induced platelet aggregation, but not for changes in their shape.

We examined the mechanisms of ATP release by human platelets using Ro-31-7549, a specific inhibitor of protein kinase C. Ro-31-7549 almost completely inhibited TPA-induced platelet aggregation and ATP release at 5–10 μM in washed platelets and in platelet-rich plasma. However, it suppressed thrombin- and U46619-induced ATP release by only 48% and 21%, respectively, and had little effect on aggregation in washed platelet suspensions containing serum or in platelet-rich plasma. The addition of GRGDS to prevent aggregation inhibited this residual thrombin-induced release by 53% and the residual U46619 release by 100% in the presence of Ro-31-7549. In washed platelet suspensions free of serum or plasma, Ro-31-7549 almost completely inhibited the ATP release and partially suppressed the aggregation induced by these agonists. These results suggested that there are protein kinase C-dependent and -independent mechanisms for ATP release by human platelets and that activation of the latter mechanism may depend on aggregation and plasma factors.

The effect of chylomicron remnants (CM-R) on apolipoprotein (apo) E synthesis by HepG2 cells was studied. The accumulation rate of apo E in the medium was increased in cells incubated with CM-R (chylo-cells) compared with that in the control cells. However, the abundance of apo E mRNA was not greater in chylo-cells than in control cells. The time course of apo E accumulation in the medium showed that apo E increased in the chylo-cells linearly up to 24 hours, whereas it increased in the control cells linearly only up to 6 hours, when it reached a plateau. The results suggest that the secretion rate of apo E was not affected by incubation with CM-R, but that uptake of the newly secreted apo E by the cells may be depressed by incubation with CM-R. Autoradiography of newly synthesized apo E showed that chylo-cells produced much more “larger” apo E than did the control cells. Two-dimensional electrophoresis of the apo E newly synthesized by the chylo-cells showed that the larger apo E was slightly acidic even after treatment with neuraminidase. Pulse-chase labeling of apo E showed that the large apo E was secreted by both control and chylo-cells equally and that the larger apo E was converted to regular apo E in the medium more effectively in control cells than in chylo-cells. In conclusion, (1) HepG2 cells produce significant amounts of acidic and larger molecular weight apo E, which may not be well recognized by the receptors on HepG2 cells; (2) the larger apo E is converted to regular apo E in the medium; and (3) the conversion of apo E may be partially inhibited as a result of incubation with CM-R.

We report that optical limiting effects of C60 in solutions depend on its environments (its concentrations and verious solvents). Its thresholds decrease with increasing of C60's concentrations. In the case of C60/Benzene or Toluene solutions, we can observe optical limiting of C60 clearly. On the other hand, in the case of C60 / N,N′-diethylaniline solution, we can not do it.

Dynamic polarization of nuclear spins has been studied in the breakdown regime of fractional quantum Hall effect using a Corbino-disk device. We find that nuclear spins are polarized in the Corbino disk in the breakdown regime of fractional quantum Hall effect. Since edge channel is completely absent in the Corbino disk, the demonstration of dynamic nuclear polarization in the Corbino disk shows that nuclear spins are polarized and detected in the bulk channel of the quantum Hall conductor.

Thapsigargin-activated Ca2+ entry into platelets was examined in the presence of S-145, a thromboxane A2 receptor antagonist, to inhibit indirect effects by endogenously formed prostaglandin H2/thromboxane A2. With external Ca2+ present, 0.2 microM thapsigargin caused a prompt increase in intracellular Ca2+ concentration ([Ca2+]i) followed by a gradual increase. Pretreatment with 6 microM wortmannin, a specific inhibitor of myosin light chain kinase, partly inhibited the increase in [Ca2+]i. In Ca(2+)-free EGTA buffer, thapsigargin induced a smaller increase in [Ca2+]i, and subsequent addition of Ca2+ to the buffer caused a further prompt increase in [Ca2+]i, demonstrating external Ca2+ entry. Wortmannin only partly inhibited this entry of external Ca2+. The wortmannin-insensitive Ca2+ entry pathway remained open for more than 6 min in Ca(2+)-free buffer. On the other hand, when receptor agonists such as thrombin and U46619 were substituted for thapsigargin, activation of the wortmannin-insensitive Ca2+ entry was transient (Hashimoto et al., J. Biol. Chem (1992) 267, 17078-17081). In the presence of S-145 and wortmannin, thapsigargin stimulated phosphorylation of neither the 20-kDa myosin light chain nor the 47-kDa protein, a substrate of protein kinase C. These results suggest that thapsigargin induces external Ca2+ entry by two mechanisms: (1) a mechanism involving myosin light chain kinase; (2) a mechanism, not activated by receptor agonists, that is independent of the major protein kinases of platelets.

The administration of 200 nM K252a to HuH7 suppressed the proliferation of the cells almost completely. The uptake of [3H]thymidine was inhibited, and flow cytometry revealed only one peak at 2C on day 3 after treatment with 100 nM K252a. The expression of proto-oncogene c-myc was not reduced. Despite the blockage at G1, both the size of the cells and the amount of cell protein had increased by 4 times by day 3 after treatment with K252a, while the cells secreted albumin and alpha-fetoprotein into the medium as usual. These results show that K252a can increase the cell size of HuH7 without losing its function by blocking the cell cycle at G1 phase.

K-252a, a protein kinase inhibitor with a wide spectrum of activity, inhibited the serum-stimulated proliferation of cultured bovine carotid endothelial cells dose-dependently, and all the cells became remarkably large, with a diameter of more than 150 μm at K-252a concentrations of 0.3-1 μg/ml. This effect of the agent was reproducible under the conditions described in this article. When the endothelial cells became abnormally large by K-252a, the surface area of the cell became wider, and the F-actin molecules increased in both number and length. Despite their abnormal size, K-252a-induced giant cells maintained at least three physiological functions characteristic to normal endothelial cells: 1) ability to take up acetylated low density lipoprotein, 2) ability to produce and secrete endothelin and 3) ability to respond via an increase of [Ca2+]i to the stimulation by bradykinin. These observations suggest that K-252a-induced giant cells are useful tools for examining the function of endothelial cells because it is very reproducible and can be produced by an easy treatment.

This paper is a continuation of Miyake [7] by the first named author. We shall study the unique solvability of an integro-differential equation in the category of formal or convergent power series with Gevrey estimate for the coefficients, and our results give some analogue in partial differential equations to Ramis [10, 11] in ordinary differential equations.In the study of analytic ordinary differential equations, the notion of irregularity was first introduced by Malgrange [3] as a difference of indices of a differential operator in the categories of formal power series and convergent power series. After that, Ramis extended his theory to the category of formal or convergent power series with Gevrey estimate for the coefficients. In these studies, Ramis revealed a significant meaning of a Newton polygon associated with a differential operator.

Low-temperature STM and STS were applied to the study of superconducting gap variations induced by perpendicular magnetic field within a microfabricated In disk. Abrupt changes of the gap observed at the disk center during magnetic field sweep are attributed to the switch between different vortex states. Spatial distribution of the superconducting gap defined by a magnetic flux configuration was also obtained. The results are partially in accordance with the distribution predicted for the giant multi-quanta vortices.

We applied giant magnetoresistance (GMR) effect to measure spin diffusion length in a non-magnetic metal. The temperature dependence of the magnetoresistance observed in Fe/Cu/Ni tri-layer samples was strongly dependent on the thickness of the middle Cu layers, apparently reflecting the spin diffusion length. Assuming the error-function dependence on the thickness, we derived the values of the spin diffusion length.

We measured electronic transport and magnetization of a metallic and ferromagnetic (Ga,Mn)As thin film epitaxially grown on a GaAs [0 0 1] substrate. In-plane ((0 0 1)) anisotropic magnetoresistance (AMR) was affected by the current direction to the crystalline, which is phenomenologically explained by the anisotropy of the magnetization. The magnetoresistance for perpendicular field showed reproducible irregular oscillations, which are attributed to the Barkhausen effect.

We demonstrate a new method for electrical manipulation of nuclear spins utilizing dynamic nuclear polarization induced by quantum Hall effect breakdown. Nuclear spins are polarized and detected through the hyperfine interaction between a nuclear spin system and a two-dimensional electron system located at an interface of GaAs/AlGaAs single heterostructure. Coherent oscillations between the nuclear-spin quantum states are observed by measuring the longitudinal voltage of the conductor., Comment: 4 pages, 2 figures

Summary Effects of protein kinase inhibitors, K252a and its derivaive KT5926, on Ca 2+ /calmodulin-dependent protein kinase II were examined. Both compounds potently inhibited Ca 2+ /calmodulin-dependent protein kinase II. Kinetic analyses indicated that the inhibitory effect of K252a and KT5926 was competitive with respect to ATP (Ki: 1.8 and 4.4 nM, respectively) and noncompetitive with respect to the substrates. Taken together with a previous report (Nakanishi et al. Mol. Pharmacol. 37, 482, 1990) concerning the Ki values of these compounds for ATP with various protein kinases, the results suggest that K252a and KT5926 are potent and preferential inhibitors of Ca 2+ /calmodulin-dependent protein kinase II.

A protease with a tetrameric quaternary structure was extracted with 1 M NaCl from spinach PS II membranes and purified by hydrophobic, anion-exchange and gel-filtration chromatography using only buffers of high ionic strength. (...)

Terahertz radiation is observed from ferromagnetic GaMnAs samples excited with 400nm wavelength pump pulses and is related to the sample magnetization M. The emission can be explained by the strong influence of M on the photogenerated carrier motion, a phenomenon related to the dc anomalous Hall effect. Results illustrate the potential of ferromagnetic materials to be used as compact terahertz sources emitting in a direction normal to the surface.

Cigarette smoking is associated with a higher risk for suicide and attempted suicide. In addition, an association between cigarette smoking and suicidal behavior across major psychiatric disorders may be related to lower brain serotonin function in smokers with depression. Unfortunately, no information is available concerning nicotine and cotinine levels in the body fluids of smokers who committed suicide. We examined the nicotine and cotinine levels in the blood and urine of 36 forensic autopsy cases with no obvious putrefaction that were handled between October 2002 and March 2004. Our cases consisted of eight smokers who committed suicide (six men, 51-76 years of age, and two women, 54A¢??79 years of age), eight smokers who did not commit suicide (seven men, 36-79 years of age, and one woman, 54 years of age), and 20 nonsmokers (15 men, 19-97 years of age, and five women, 62-82 years of age). One suicide case was present in the nonsmoking group. None of the suicide smokers consumed nicotine preparations or tobacco leaves. Eight suicide smokers had high levels of nicotine and cotinine in their blood (mean=115 ng/ml, SD=49, and mean=405 ng/ml, SD=291, respectively) and urine (mean=1940 ng/ml, SD=2540, and mean=1170 ng/ml, SD=1570, respectively). In contrast, eight nonsuicide smokers had lower levels of nicotine and cotinine in their blood (mean=30.1 ng/ml, SD=17.7, and mean=122 ng/ml, SD=65, respectively) and urine (mean=383 ng/ml, SD=417, and mean=170 ng/ml, SD=86, respectively). Blood nicotine levels in our eight suicide smokers were significantly higher than in nonsuicide smokers (t=4.61, df=14, p=0.0004). Although urine nicotine level and blood and urine cotinine levels were higher in suicide than nonsuicide smokers, they did not achieve a level of statistical significance. Our data, although they are preliminary and limited in number, strongly suggest that a marked increase in cigarette smoking in persons with psychiatric disorders may be a sign of an imminent suicide attempt. The smoking status of psychiatric patients may serve as a clinical sign of their mental status and provide an early warning sign of a possible suicide attempt.

We describe the case of a 71-year-old man who was being followed as an outpatient for type 2 diabetes, hyperlipidemia, hypertension, and asthma. He was a past smoker with a BMI of 25.6 kg/m2. Because he had only mild wheezing at night, he was not under medical treatment for asthma. As his level of HbA1c remained between 6.6 and 6.8% under treatment with 2.5 mg glibenclamide, 30 mg pioglitazone (an insulin-sensitizing drug) was added to his treatment. Several days later, he noticed that his wheezing had disappeared. The pulmonary function tests showed improvement of forced vital capacity from 2.33 to 3.02 l and forced expiratory volume in …

This paper describes the tissue distributions of dichlorvos, an organophosphate, chlorpyrifos-methyl, an organophosphorothioate, methomyl, a carbamate, and endrin, an organochlorine, in three individuals (Cases 1-3) who died after ingesting insecticidal preparations containing these chemicals. In Case 1 involving dichlorvos and chlorpyrifos-methyl, no dichlorvos was detected in most of the blood and tissue samples. Tiny amounts of dichlorvos (0.067 mg/L and 0.027 mg/L) were detected in the vitreous humor and cerebrospinal fluid, respectively. The chlorpyrifos-methyl concentrations in the blood samples were very site-dependent with a range of 0.615-2.24 mg/L. The tissue concentrations of chlorpyrifos-methyl were within the range 0.379-8.60 mg/kg. The total amounts of dichlorvos and chlorpyrifos-methyl in the stomach were 879 and 612 mg, respectively. The serum cholinesterase activity was 3 IU/L/37 degrees C. In Case 2 involving methomyl, the methomyl concentrations in the blood samples were very site-dependent with a range of 0.56-4.75 mg/L. The tissue concentrations of methomyl were 2.61 mg/kg or less, no methomyl being detected in the spleen, liver and kidney. The methomyl concentrations in the cerebrospinal fluid and vitreous humor were 5.37 and 4.75 mg/L, respectively. The stomach contained 85 mg methomyl. The serum cholinesterase activity was 73 IU/L/37 degrees C. In Case 3 involving endrin, the victim underwent medical treatment for 7 h after ingesting an endrin preparation. The differences in the endrin concentrations among the blood samples were small, with a range of 0.353-0.615 mg/L. The tissue concentrations of endrin were within the range 0.467-13.3 mg/kg. The endrin in the stomach (66 mg) was adsorbed almost completely on the activated charcoal that was administered for medical treatment.

The purpose of this study was to determine whether lidocaine is absorbed from the trachea during the artificial circulation of cardiopulmonary resuscitation. The tissue distribution of lidocaine was investigated in eight individuals (Cases 1-8) who underwent cardiopulmonary resuscitation before being pronounced dead. In Cases 1-4, there was no restoration of heart beat during cardiopulmonary resuscitation. Heart massage had been continued for 5 min in Cases 1 and 2, and for 60 min in Cases 3 and 4. Relatively high concentrations of lidocaine (more than 0.1 mg/L) were detected in the blood left in the heart and/or in the large thoracic vessels in the four cases. In Cases 1-3, a large proportion of the lidocaine detected in these blood samples may have diffused from the trachea after cessation of cardiopulmonary resuscitation since no lidocaine was detected in the cerebrospinal fluid, cerebrum, liver, right kidney, and/or right femoral muscle. In Case 4, however, tracheal lidocaine was thought to have been absorbed during cardiopulmonary resuscitation because 0.167-0.340 mg/L or mg/kg lidocaine was detected in the cerebrospinal fluid, liver, right kidney, and right femoral muscle. This was substantiated in experiments performed in rabbit carcasses given 50 microL/kg Xylocaine jelly (a 2% lidocaine hydrochloride preparation) intratracheally, followed by rhythmical thoracic compressions (100-150 times per minute) for 60 min. A possible reason for lack of absorption of lidocaine from the trachea of Case 3 during a 60-min cardiopulmonary resuscitation procedure may have been that effective blood circulation was not obtained during cardiopulmonary resuscitation because of bleeding and pulmonary collapse. Cases 5-8 survived for 3 h to 10 days after successful cardiopulmonary resuscitation; it was obvious that lidocaine was distributed to the tissues under the influence of the natural circulation. The kidney to liver lidocaine ratio in Case 4 (0.8) was much lower than that in Cases 5-8 (1.3-4.6), although the lidocaine ratio in the blood in the left ventricle when compared to blood in the right ventricle was similar in the five cases. The kidney to liver lidocaine ratio may be helpful in judging whether the lidocaine detected was absorbed during the artificial circulation of cardiopulmonary resuscitation or naturally. Additionally, postmortem diffusion of tracheal lidocaine into the blood in the left ventricle was much greater than into the blood in the right ventricle due to their anatomical location during a supine position. The pattern of tissue distribution of lidocaine gives useful information on the state of decedents during cardiopulmonary resuscitation.

The tissue distribution of free and conjugated morphine in a male individual who died after self-injection of heroin and methamphetamine was investigated, and the postmortem stability of morphine in the blood, liver and urine, and that of 6-monoacetylmorphine in the urine was determined. Confirmation and quantitation of morphine, 6-monoacetylmorphine and methamphetamine were performed by gas chromatography/mass spectrometry and gas chromatography, respectively. Blood levels of free and total morphine were very site-dependent with ranges of 462-1350 and 534-1570 ng/mL, respectively. Large amounts of total morphine, 5220, 4200, and 2270 ng/g, had accumulated in the stomach contents, liver, and lung, respectively. The concentration of free morphine in the cerebrospinal fluid was correlated very closely with that in the cerebrum. The proportion of free morphine in various fluids and tissues ranged from 23.0% to 98.8% of total morphine: less than 30% in the stomach contents and urine; 30-60% in the liver, cerebrospinal fluid, lung, and pericardial sac fluid; 61-90% in the spleen, right femoral muscle, myocardium, blood in the left and right ventricles of the heart, and right femoral vein blood; more than 91% in the right kidney and cerebrum. Detectable amounts of 6-monoacetylmorphine, 417 ng/mL and 78 ng/g, existed in the urine and stomach contents, respectively, indicating that this individual might have died within several hours after heroin injection. Methamphetamine concentrations in the blood were also site-dependent within the range 551-1730 ng/mL. In an in vitro experiment, free and conjugated morphine were stable in the blood and urine at 4, 18-22, and 37 degrees C for a 10-day study period. In the liver, however, conjugated morphine had been converted almost completely to free morphine at 18-22 and 37 degrees C by the end of the experiment, although it was stable at 4 degrees C. Urine 6-monoacetylmorphine, although degraded slightly at 37 degrees C, was stable at 4 and 18-22 degrees C during the experiment. Thus it appears that non-specific hydrolysis of conjugated morphine to free morphine would not occur in corpses at least for a few days after death. Femoral muscle may be a specimen of choice for roughly predicting the ratio of free to total morphine in blood even when blood specimens are not available, because the femoral muscle is relatively spared of both postmortem diffusion of drugs and bacterial invasion.

We present the theory behind and discuss experimentation on the spectral control of a laser diode with a Michelson external cavity. This structure is advantageous in terms of variable resonance mode spacing and the wavelength tuning range achieved by adjusting the path-length difference of the external cavity. This laser diode is easy to construct and uses mainly inexpensive components. In theory, we replace the end facet of the laser medium and the mirrors of the external cavity with an equivalent mirror, and therefore, resonance conditions of the laser diode with the external cavity can be analyzed. Through experiment, we investigated dependences of the bandwidth and wavelength tuning range of the laser diode on the path-length difference of the external cavity and the injection current. We achieved a 0.75 nm extension of the wavelength tuning range and a 1/6 reduction in the bandwidth.