The excitation intensity dependence of singlet fission dynamics of a rubrene microcrystal studied by femtosecond transient microspectroscopy.

We have investigated the excitation intensity dependence of the singlet fission in a crystalline rubrene by means of femtosecond transient absorption microspectroscopy. When a rubrene microcrystal was excited to higher energy levels than that of the lowest singlet excited (S1) state with a 397 nm femtosecond laser pulse, a triplet excited state was formed through two pathways of the singlet fission, i.e. the direct fission from higher vibrational levels of the S1 state with a time constant of 2.2 ps and the thermally activated fission from the S1 state in a few tens of ps. The time constant of the thermally activated fission changed from 35 to 17 ps for increasing of the laser fluence from 0.65 to 18 mJ cm-2 per pulse, although that of the direct fission was constant with the excitation laser intensity. On the other hand, the yield of the triplet formation was independent of the intensity. We also examined the temperature dependence of the singlet fission and demonstrated the activation energy of the thermally activated fission to be 0.21 eV. Based on the experimental results, we considered the excitation intensity dependence of the singlet fission of the rubrene crystal in terms of the effect of transient local heating on a ps time scale after femtosecond laser excitation owing to the nonradiative vibrational relaxation from the higher vibrational level to the lower one in the S1 state.

Valacyclovir neurotoxicity: clinical experience and review of the literature.

Valacyclovir (VACV) is used increasingly to treat herpes zoster, although neuropsychiatric symptoms [VACV neurotoxicity (VAN) or acyclovir neurotoxicity], may accompany use of this drug. To promote awareness of this rare condition, we describe here two clinical cases of VAN we previously reported and review 20 cases from the literature. In all cases, chronic or acute renal failure preceded VAN. The symptoms of VAN varied, but disturbances of consciousness and hallucination occurred most commonly. When acute renal failure was due to the drug, recovery from both the disturbance of consciousness and renal failure followed within several days after discontinuation of VACV. Early recognition and diagnosis will ensure effective treatment of VAN.

Laser fabrication and spectroscopy of organic nanoparticles.

In working with nanoparticles, researchers still face two fundamental challenges: how to fabricate the nanoparticles with controlled size and shape and how to characterize them. In this Account, we describe recent advances in laser technology both for the synthesis of organic nanoparticles and for their analysis by single nanoparticle spectroscopy. Laser ablation of organic microcrystalline powders in a poor solvent has opened new horizons for the synthesis of nanoparticles because the powder sample is converted directly into a stable colloidal solution without additives and chemicals. By tuning laser wavelength, pulse width, laser fluence, and total shot number, we could control the size and phase of the nanoparticles. For example, we describe nanoparticle formation of quinacridone, a well-known red pigment, in water. By modifying the length of time that the sample is excited by the laser, we could control the particle size (30-120 nm) for nanosecond excitation down to 13 nm for femtosecond irradiation. We prepared beta- and gamma-phase nanoparticles from the microcrystal with beta-phase by changing laser wavelength and fluence. We present further results from nanoparticles produced from several dyes, C(60), and an anticancer drug. All the prepared colloidal solutions were transparent and highly dispersive. Such materials could be used for nanoscale device development and for biomedical and environmental applications. We also demonstrated the utility of single nanoparticle spectroscopic analysis in the characterization of organic nanoparticles. The optical properties of these organic nanoparticles depend on their size within the range from a few tens to a few hundred nanometers. We observed perylene nanoscrystals using single-particle spectroscopy coupled with atomic force microscopy. Based on these experiments, we proposed empirical equations explaining their size-dependent fluorescence spectra. We attribute the size effect to the change in elastic properties of the nanocrystal. Based on the results for nanoparticles of polymers and other molecules with flexible conformations, we assert that size-dependent optical properties are common for organic nanoparticles. While "electronic confinement" explains the size-dependent properties of inorganic nanoparticles, we propose "structural confinement" as an analogous paradigm for organic nanoparticles.

Diagnostic utility of brain-natriuretic peptide for left ventricular diastolic dysfunction in asymptomatic type 2 diabetic patients.

AIM: Left ventricular (LV) diastolic dysfunction has been reported to be prevalent in diabetic subjects, but this recognition could often be missed. We evaluated prevalence of LV diastolic dysfunction and diagnostic utility of brain-natriuretic peptide (BNP) in asymptomatic patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: Plasma BNP levels and LV geometry and diastolic filling indices, including the ratio of peak early transmitral Doppler flow (E) over flow propagation velocity (Vp) measured by colour M-mode Doppler echocardiography, were analysed in 98 consecutive asymptomatic patients with type 2 diabetes mellitus and 51 age-matched controls. RESULTS: The LV mass index and relative wall thickness were higher in diabetic groups than controls without any differences in LV systolic function. The frequency of diastolic dysfunction defined as E/Vp > or = 1.5 were 31% in diabetic groups and 15% in controls (chi(2) = 4.364, p = 0.037). By receiver-operating characteristic (ROC) curve analysis, a BNP cutoff value of 19.2 pg/ml in controls had a 53.1% positive predictive value (53.1%) and a high negative predictive value (94.4%) for E/Vp >/= 1.5, whereas a BNP cutoff value of 18.1 pg/ml in diabetic groups had a 61.8% positive and 97.3% negative predictive values. CONCLUSIONS: The frequency of E/Vp > or = 1.5 was higher in asymptomatic diabetic patients, suggesting that LV diastolic dysfunction was prevalent. The plasma concentration of BNP could be used to depict LV diastolic dysfunction in such population.

Neuronal responses to a delayed-response delayed-reward go/nogo task in the monkey posterior insular cortex.

Anatomical connections of the insular cortex suggest its involvement in cognition, emotion, memory, and behavioral manifestation. However, there have been few neurophysiological studies on the insular cortex in primates, in relation to such higher cognitive functions. In the present study, neural activity was recorded from the monkey insular cortex during performance of a delayed-response delayed-reward go/nogo task. In this task, visual stimuli indicating go or nogo responses associated with reward (reward trials) and with no reward (no-reward trials) were presented after eye fixation. In the reward trials, the monkey was required to release a button during presentation of the 2nd visual stimuli after a delay period (delay 1). Then, a juice reward was delivered after another delay (delay 2). The results indicated that the neurons responding in each epoch of the task were topographically localized within the insular cortex, consistent with the previous anatomical studies indicating topographical distributions of afferent inputs from other subcortical and cortical sensory areas. Furthermore, some insular neurons 1) nonspecifically responded to the visual cues and during fixation; 2) responded to the visual cues predicting reward and during the delay period before reward delivery; 3) responded differentially in go/nogo trials during the delay 2; and 4) responded around button manipulation. The observed patterns of insular-neuron responses and the correspondence of their topographical localization to those in previous anatomical studies suggest that the insular cortex is involved in attention- and reward-related functions and might monitor and integrate activities of other brain regions during cognition and behavioral manifestation.

Efficacy of a navigation system in neuro-endoscopic surgery.

OBJECTIVE: Neuro-endoscopy is playing a greater role in the diagnosis and treatment of several types of lesions, especially in the ventricular system. However, surgical planning and intraoperative orientation during endoscopic surgery are sometimes difficult. The efficacy of a neurosurgical navigation system using three-dimensional computer graphics of magnetic resonance (MR) images in neuro-endoscopic surgery was evaluated in this study. METHODS: We have developed a navigational endoscopic system designed to monitor the tip and direction of the endoscope, with the mirror marker of the navigation connected to a rigid endoscope. Eight patients, 3 cases of aqueductal stenting for isolated fourth ventricle, 3 cases of cystostomy for ependymal cyst, 1 case of septostomy for isolated lateral ventricle, and 1 case of ventricular tap in narrow ventricles, underwent endoscopic surgery using the present system. RESULTS: All patients underwent successful procedures with good outcomes. The present system was very useful in the cases of an accurate ventricular tap in narrow ventricles, identification of anatomic structures, and determining the appropriate route to the target point. CONCLUSIONS: This navigational endoscopic system improved the safety and accuracy of neuro-endoscopic surgery.

Impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas: a single-institution retrospective study.

Neuronavigation has become an effective therapeutic modality and is used routinely for intra-axial tumor removal. This retrospective study was conducted to evaluate the clinical impact of neuronavigation and image-guided extensive resection for adult patients with supratentorial malignant astrocytomas. Between 1990 and 2002, 76 adult patients with pathologically confirmed malignant astrocytomas underwent craniotomy and removal of the tumors at the Toyama Medical and Pharmaceutical University Hospital. Of these 76 patients, 42 were treated using neuronavigation with conventional microneurosurgery and the other 34 were treated with conventional microneurosurgery alone. Postoperative early MRI with contrast enhancement was done, and gross total resection was defined as the complete absence of residual tumor. Survival time was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from the Cox proportional hazards model. In univariate analysis, age (< 65), grade 3, preoperative KPS (>/= 80), use of neuronavigation, and gross total resection were significantly associated with longer survival. However, when the data were submitted to multivariate analysis, grade 3, preoperative KPS (>/= 80), and gross total resection were independent prognostic factors. The median survival periods of patients receiving gross total resection (vs. partial resection) and neuronavigation (vs. no neuronavigation) were 16 (vs. 9) months and 16 (vs. 10) months, respectively. The percentage of a gross total resection was significantly higher in the neuronavigation group compared to that in the no-navigation group (64.3 % vs. 38.2 %, p < 0.05). Neurological deterioration occurred in 4 of 42 (9.5 %) and in 6 of 34 (17.6 %) patients after surgery with neuronavigation and surgery without neuronavigation, respectively, although this difference was not statistically significant. Our results showed that neuronavigation increases the radicality in the resection of malignant astrocytomas and is objectively useful for improving survival time.

Triiodothyronine concomitantly inhibits calcium overload and postischemic myocardial stunning in diabetic rats.

Acute effects of triiodothyronine (T3) on postischemic myocardial stunning and intracellular Ca2+ contents were studied in the isolated working hearts of streptozotocin-induced diabetic rats and age-matched controls. After two weeks of diabetes, serum T3 and T4 levels were decreased to 62.5% and 33.9% of control values. Basal preischemic cardiac performance did not differ between diabetic and control rats. In contrast, during reperfusion after 20-min ischemia, diabetic rats exhibited an impaired recovery of heart rate (at 30-min reperfusion 57.5% of baseline vs. control 88.5%), left ventricular (LV) systolic pressure (44.1% vs. 89.5%), and cardiac work (23.1% vs. 66.0%). When 1 and 100 nM T3 was added before ischemia, heart rate was recovered to 77.2% and 81.8% of baseline, LV systolic pressure to 68.3% and 81.9%, and cardiac work to 50.8% and 59.0%, respectively. Diabetic rat hearts showed a higher Ca2+ content in the basal state and a further increase after reperfusion (4.96+/-1.17 vs. control 3.78+/-0.48 micromol/g, p<0.01). In diabetic hearts, H+ release was decreased after reperfusion (5.24+/-2.21 vs. 8.70+/-1.41 mmol/min/g, p<0.05). T3 administration caused a decrease in the postischemic Ca2+ accumulation (lnM T3 4.66+/-0.41 and 100 nM T3 3.58+/-0.36) and recovered the H+ release (lnM T3 16.2+/-3.9 and 100 nM T3 11.6+/-0.9). T3 did not alter myocardial O2 consumption. Results suggest that diabetic rat hearts are vulnerable to postischemic stunning, and T3 protects the myocardial stunning possibly via inhibiting Ca2+ overload.

Malignant transformation of cerebello-pontine angle epidermoid.

A 55-year-old woman presented with fever and a stiff neck due to an intracranial poorly differentiated carcinoma at the right cerebellopontine angle. The patient suffered from typical trigeminal pain and had undergone a removal of the right cerebellopontine angle epidermoid 13 years before at another hospital. On admission, MRI imaging showed a lesion at the right cerebellopontine angle with marked contrast enhancement. Partial removal of the tumor was achieved. A histological examination of the tumor showed a poorly differentiated carcinoma accompanied by typical desquamated tissue of the epidermoid. The patient died 3 months after the operation because of aggressive meningeal carcinomatosis.

A deficiency of coproporphyrinogen III oxidase causes lesion formation in Arabidopsis.

We isolated an Arabidopsis lesion initiation 2 (lin2) mutant, which develops lesion formation on leaves and siliques in a developmentally regulated and light-dependent manner. The phenotype of the lin2 plants resulted from a single nuclear recessive mutation, and LIN2 was isolated by a T-DNA tagging approach. LIN2 encodes coproporphyrinogen III oxidase, a key enzyme in the biosynthetic pathway of chlorophyll and heme, a tetrapyrrole pathway, in Arabidopsis. The lin2 plants express cytological and molecular markers associated with the defense responses, usually activated by pathogen infection. These results demonstrate that a porphyrin pathway impairment is responsible for the lesion initiation phenotype, which leads to the activation of defense responses, in Arabidopsis. Lesion formation was not suppressed, and was even enhanced when accumulation of salicylic acid (SA) was prevented in lin2 plants by the expression of an SA-degrading salicylate hydroxylase (nahG) gene. This suggests that the lesion formation triggered in lin2 plants is determined prior to or independently of the accumulation of SA but that the accumulation is required to limit the spread of lesions in lin2 plants.

Enantioselective fluorination mediated by cinchona alkaloid derivatives/Selectfluor combinations: reaction scope and structural information for N-fluorocinchona alkaloids.

Cinchona-alkaloid/Selectfluor combinations efficiently fluorinate a variety of carbonyl compounds in a highly enantioselective manner to furnish chiral alpha-fluorocarbonyl compounds. The DHQB/Selectfluor combination is effective for the enantioselective fluorination of indanones and tetralones 1 in up to 91% ee. The first enantioselective syntheses of chiral derivatizing reagents 3 was accomplished with high ee and in high chemical yields by the DHQDA/Selectfluor combination. 3-Fluorooxindoles 7 were prepared with ee up to 83% using the (DHQ)2AQN/Selectfluor or the (DHQD)2PYR/Selectfluor combination. Since the combinations are conveniently prepared in situ from readily available reagents, the present system represents a practical method for enantioselective fluorination. X-ray crystallography and 1H NMR analyses of the cinchona alkaloids/Selectfluor combination have established that the species that mediate this novel reaction are N-fluoroammonium cinchona alkaloid tetrafluoroborates, which adopt open conformations.

Primary photoreaction of photoactive yellow protein studied by subpicosecond-nanosecond spectroscopy.

The primary photochemical event of photoactive yellow protein (PYP) was studied by laser flash photolysis experiments on a subpicosecond-nanosecond time scale. PYP was excited by a 390-nm pulse, and the transient difference absorption spectra were recorded by a multichannel spectrometer for a more reliable spectral analysis than previously possible. Just after excitation, an absorbance decrease due to the stimulated emission at 500 nm and photoconversion of PYP at 450 nm were observed. The stimulated emission gradually shifted to 520 nm and was retained up to 4 ps. Then, the formation of a red-shifted intermediate with a broad absorption spectrum was observed from 20 ps to 1 ns. Another red-shifted intermediate with a narrow absorption spectrum was formed after 2 ns and was stable for at least 5 ns. The latter is therefore believed to correspond to I1 (PYP(L)), which has been detected on a nanosecond time scale or trapped at -80 degrees C. Singular value decomposition analysis demonstrated that the spectral shifts observed from 0.5 ps to 5 ns could be explained by two-component decay of excited state(s) and conversion from PYP(B) to PYP(L). The amount of PYP(L) at 5 ns was less than that of photoconverted PYP, suggesting the formation of another intermediate, PYP(H). In addition, the absorption spectra of these intermediates were calculated based on the proposed reaction scheme. Together, these results indicate that the photocycle of PYP at room temperature has a branched pathway in the early stage and is essentially similar to that observed under low-temperature spectroscopy.

[Phase I study of amrubicin hydrochroride (SM-5887) for superficial bladder cancer in intravesical chemotherapy].

A phase I study of intravesical chemotherapy with amrubicin hydrochloride for superficial bladder cancer was conducted. Amrubicin was dissolved in 30 ml of physiological saline and injected intravesically on 6 consecutive days. The drug solution was retained for 2 hours. The starting dose was 60 mg/day, and the dose was escalated to 150 mg/day in 30 mg/day increments. Fifteen patients were entered into this study, of whom 14 were eligible and assessable for toxicity, and 13 were assessable for efficacy. The incidence and severity of cystic irritabilities such as micturition pain, pollakisuria and hematuria were related to the doses of amrubicin. At 150 mg/day, one of three patients experienced grade 3 micturition pain and pollakisuria. The dose-limiting toxicities, therefore, were micturition pain and pollakisuria, and the maximal tolerated dose was estimated to be 150 mg/day, considering that none of the three patients could retain the drug solution for 2 hours. One complete response and four partial responses were obtained in 13 assessable patients, and the overall response rate was 38.5%. A breakdown according to the doses was as follows. One PR of 3 patients were achieved at 60 and 90 mg/day, respectively 2 PRs of 5 patients at 120 mg/day, and one CR of 2 patients at 150 mg/day.

[Early phase II study of amrubicin (SM-5887) for superficial bladder cancer: a dose-finding study for intravesical chemotherapy].

An early phase II study (dose-finding study) of amrubicin hydrochloride for superficial bladder cancer was conducted. Amrubicin was dissolved in 30 ml of physiological saline and injected intravesically for 6 consecutive days. The drug solution was retained for 2 hours. Patients were randomly assigned to four groups, which were administered amrubicin at doses of 30, 60, 90, and 120 mg/day, respectively. Of 65 patients registered in this study, 63 were eligible and assessable for toxicities, and 55 assessable for efficacy. The response rate at each dose level was 50.0% (7PRs/14 patients) at 30 mg/day, 53.3% (8 PRs/15) at 60 mg/day, 61.5% (2 CRs + 6 PRs/13) at 90 mg/day, and 69.2% (2 CRs + 7 PRs/13) at 120 mg/day, respectively. These data suggests that the efficacy was related to the doses of amrubicin. The major toxicities were cystic irritabilities, such as micturition pain, pollakisuria and hematuria. These toxicities were related to the doses of amrubicin. Their incidence and the severity were not high compared with those reported about other anthracyclines such as doxorubicin and epirubicin. The optimal dose of amrubicin was estimated to be 90 to 120 mg/day in the intravesical treatment for superficial bladder cancer once a day for 6 consecutive days.

A walking stick for a pure akinesia patient.

We describe a 63-year-old female patient with pure akinesia whose gait was facilitated by a handmade converted walking stick. A posterior ventral pallidotomy had been performed, but it did not alleviate symptoms. Her husband made a walking stick with a wire loop at the bottom, perpendicular to the walking direction. When the patient stepped over the loop, the frozen gait was improved. This converted walking stick is easily made and inexpensive. Although the walking stick did not improve the patient's gait radically, use of the converted walking stick effectively improved the patient's daily life because successful treatment of pure akinesia cannot be established.

Cilazapril prevents cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats.

We evaluated the effects of hyperthyroidism on cardiac structural changes and postischemic myocardial function, and also studied how an angiotensin-converting enzyme (ACE) inhibitor, cilazapril, can alter these changes. Hyperthyroidism was induced by daily intraperitoneal injection of thyroxine (T4) (600 microg/kg) with or without cilazapril (10 mg/kg per day, orally), and control rats were given by vehicle. After 2 weeks of treatment, T4-treated rats showed increases in blood pressure and heart weight to body weight ratio (HW:BW). Cilazapril decreased blood pressure to control values and reduced HW:BW. In the isolated working heart preparation, T4-treated rats showed a poor postischemic recovery of left ventricular pressure-rate product (14% of baseline at 30 minutes of reperfusion vs. vehicle 85%) and cardiac work (6% vs. 71%). Cilazapril recovered both values to 49% and 43%. Propranolol (500 mg/L in drinking water) decreased blood pressure to the same extent as cilazapril in hyperthyroid rats, but changed neither HW:BW nor the postischemic myocardial dysfunction. Percent recovery of cardiac work was inversely well correlated with HW:BW (R2 = 0.998, p < 0.001). Results indicate that T4-induced cardiac hypertrophy enhances postischemic cardiac dysfunction. Results also indicate renin-angiotensin system (RAS), but not sympathetic nerve activation, is involved in cardiac hypertrophy and postischemic myocardial dysfunction in hyperthyroid rats.

Multiple dural arteriovenous fistulae involving the cavernous and sphenoparietal sinuses.

A 72-year-old woman who presented with a unilateral oculomotor nerve palsy was shown to have a very rare condition: multiple dural arteriovenous fistulae (DAVF) involving the cavernous and sphenoparietal sinuses. The sphenoparietal DAVF was cured completely by transarterial embolisation. Symptomatic relief was accomplished by this procedure. The cavernous sinus DAVF progressed to acquire cortical venous drainage, and was obliterated completely by transvenous embolisation.

Molecular cloning and characterization of a cDNA for a rice Sec31p homolog.

A cDNA for a putative Sec31p in rice has been cloned and sequenced. In yeast, Sec31p is a component of a protein-coated vesicle, COPII, which functions in the transport of cargo proteins from the endoplasmic reticulum to the cis-Golgi network. Structural similarities between yeast Sec31p and the rice putative homolog are discussed.