Observation of the magnon Hall effect.

The Hall effect usually occurs in conductors when the Lorentz force acts on a charge current in the presence of a perpendicular magnetic field. Neutral quasi-particles such as phonons and spins can, however, carry heat current and potentially exhibit the thermal Hall effect without resorting to the Lorentz force. We report experimental evidence for the anomalous thermal Hall effect caused by spin excitations (magnons) in an insulating ferromagnet with a pyrochlore lattice structure. Our theoretical analysis indicates that the propagation of the spin waves is influenced by the Dzyaloshinskii-Moriya spin-orbit interaction, which plays the role of the vector potential, much as in the intrinsic anomalous Hall effect in metallic ferromagnets.

Noxious cold stimulation induces mitogen-activated protein kinase activation in transient receptor potential (TRP) channels TRPA1- and TRPM8-containing small sensory neurons.

Two cold-sensitive transient receptor potential (TRP) channels, TRPA1 and TRPM8, have been identified and considered interesting because of their possible roles in thermosensation, nociception and other functions. Recently, we have reported that the phosphorylation of extracellular signal-regulated protein kinase and p38 mitogen-activated protein kinase occurred in primary afferent neurons in response to noxious heat stimulation of the peripheral tissue, i.e. activity-dependent activation of extracellular signal-regulated protein kinase and p38 in dorsal root ganglion neurons. In the present study, we investigated the phosphorylation of extracellular signal-regulated protein kinase, p38, and c-Jun N-terminal kinase in the rat dorsal root ganglion by cold stimulation using immunohistochemistry. Cold stimuli (28-4 degrees C) were applied by immersion of the hind paw into a water bath (six times of 10 s stimulation and 10 s interval, total 2 min). Noxious cold stimulation induced phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38, but not phosphorylated-c-Jun N-terminal kinase, in small to medium diameter sensory neurons with a peak at 2 min after stimulation. We found that a cold stimulation at 4 degrees C showed a marked increase in the number of activated neurons. Furthermore, double staining for phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38 showed no colocalization in the dorsal root ganglion neurons. We then performed double-labeling experiments for TRPA1 and TRPM8 mRNA and phosphorylation of mitogen-activated protein kinase. The majority of phosphorylated-extracellular signal-regulated protein kinase-positive neurons also expressed TRPM8 mRNA, whereas phosphorylated-p38 heavily colocalized with TRPA1 mRNA after noxious cold stimulation. Our data suggest that the noxious, but not innocuous, cold stimulation in vivo induced differential activation of extracellular signal-regulated protein kinase and p38 pathways in each subpopulation containing TRPA1 or TRPM8 in dorsal root ganglion.

The effect of site and type of nerve injury on the expression of brain-derived neurotrophic factor in the dorsal root ganglion and on neuropathic pain behavior.

A number of rat neuropathy models have been developed to simulate human neuropathic pain conditions, such as spontaneous pain, hyperalgesia, and allodynia. In the present study, to determine the relative importance of injury site (proximal or distal to the primary afferent neurons) and injury type (motor or sensory), we examined pain-related behaviors and changes of brain-derived neurotrophic factor expression in the dorsal root ganglion in sham-operated rats, and in the L5 dorsal rhizotomy, L5 ventral rhizotomy, L5 dorsal rhizotomy+ventral rhizotomy, and L5 spinal nerve transection models. L5 ventral rhizotomy and spinal nerve transection produced not only mechanical and heat hypersensitivity, but also an increase in brain-derived neurotrophic factor mRNA/protein in the L5 dorsal root ganglion at 7 days after surgery. In contrast, rats in the L5 dorsal rhizotomy and dorsal rhizotomy+ventral rhizotomy groups did not show both pain behaviors at 7 days after surgery, despite brain-derived neurotrophic factor upregulation in medium- and large-size neurons in the L5 dorsal root ganglion. On the other hand, L5 spinal nerve transection, but not dorsal rhizotomy, dorsal rhizotomy+ventral rhizotomy or ventral rhizotomy, increased the expression of brain-derived neurotrophic factor in the L4 dorsal root ganglion at 7 days after surgery. Taken together, these findings suggest that the upregulation of brain-derived neurotrophic factor expression in the L4 and L5 dorsal root ganglion neurons may be, at least in part, involved in the pathophysiological mechanisms of neuropathic pain and that the selective nerve root injury models may be useful for studying the underlying mechanisms of chronic pain after nerve injury.

Analysis of the epidermal growth factor receptor promoter: the effect of nuclear factor-kappaB.

The epidermal growth factor receptor gene is highly regulated and responsive to extracellular stimuli that control cell growth. We have identified five putative nuclear factor-kappaB (NF-kappaB) binding sites within the epidermal growth factor receptor (EGFR) promoter region by sequence analysis. We have analyzed the potential role of NF-kappaB family members in the regulation of the EGFR transcription. Electrophoretic mobility shift analysis demonstrated that the p50 and p49, subunit proteins of the NF-kappaB, bound to the EGFR promoter at four out of five of these sites. However, it was found that NF-kappaB could not transactivate the EGFR by cotransfection experiments with each NF-kappaB subunit, using p50, p65 and c-Rel and an EGFR promoter luciferase reporter. Treatment of cells with tumor necrosis factor (TNF)-alpha, which could degrade the I-kappaB and then result in translocation of NF-kappaB to nucleus, did not enhance EGFR promoter reporter gene transcription. Also, TNF-alpha did not induce EGFR expression at the protein level. These results indicate that even though purified NF-kappaB can bind to the putative sites, there is no evidence that NF-kappaB transactivates the EGFR promoter region.

Early Growth Response-1 gene mediates up-regulation of epidermal growth factor receptor expression during hypoxia.

Hypoxia occurs during development of cancers and is correlated with cancer progression. Hypoxia also induces epidermal growth factor receptor (EGFR) expression. The EGFR plays a vital role in cell growth, and its overexpression can lead to transformation. We sought to determine the regulator(s) of EGFR expression during hypoxia. We demonstrate that early growth response factor 1 (Egr-1), which is induced by hypoxia, can activate the basal transcriptional activity of the EGFR promoter. Egr-1 not only transactivates the EGFR promoter activity but also enhances endogenous EGFR expression. Using a series of EGFR promoter deletion mutants, we show that the region between -484 and -389, which contains a putative Egr-1 consensus motif, is crucial for EGFR transactivation by Egr-1. Electrophoretic mobility shift assays show that Egr-1 binds to the oligonucleotide containing this Egr-1 motif. Also, introduction of an antisense oligonucleotide for Egr-1 diminishes EGFR expression during hypoxia, indicating that the up-regulation of EGFR by hypoxia is mediated through Egr-1. Our results provide evidence that regulation of EGFR promoter activity by Egr-1 represents a mechanism for epidermal cell growth during hypoxia.

In vitro antimicrobial activities of bakuchiol against oral microorganisms.

Bakuchiol was isolated from the seeds of Psoralea corylifolia, a tree native to China with various uses in traditional medicine, followed by extraction with ether and column chromatography combined with silica gel and octyldecyl silane. In this study, the antimicrobial activities of bakuchiol against some oral microorganisms were evaluated in vitro. The cell growth of Streptococcus mutans was inhibited in a bakuchiol concentration-dependent manner, and growth of S. mutans was completely prevented by 20 microg of bakuchiol per ml. The bactericidal effect of bakuchiol on S. mutans was dependent on temperature and stable under the following conditions: sucrose, 0 to 10% (wt/vol); pH, 3.0 to 7.0; organic acids (3% [wt/vol] citric and malic acids). Bakuchiol showed bactericidal effects against all bacteria tested, including S. mutans, Streptococcus sanguis, Streptococcus salivarius, Streptococcus sobrinus, Enterococcus faecalis, Enterococcus faecium, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Actinomyces viscosus, and Porphyromonas gingivalis, with MICs ranging from 1 to 4 microg/ml and the sterilizing concentration for 15 min ranging from 5 to 20 microg/ml. Furthermore, bakuchiol was also effective against adherent cells of S. mutans in water-insoluble glucan in the presence of sucrose and inhibited the reduction of pH in the broth. Thus, bakuchiol would be a useful compound for development of antibacterial agents against oral pathogens and has great potential for use in food additives and mouthwash for preventing and treating dental caries.

Factors determining outcome in elderly patients with severe COPD on long-term domiciliary oxygen therapy.

The objective of the present study was to identify factors that determine outcome in elderly patients receiving long term domiciliary oxygen therapy (LTOT) for chronic obstructive pulmonary disease (COPD). One hundred fifty-seven COPD patients (121 male, 36 female) receiving LTOT were followed-up from 1983 to 1994. Univariate and multivariate analysis by Cox's proportional hazards ratio model and Kaplan-Meier survival estimates were used to quantify the relationship among a total of 34 baseline variables and overall mortality. By December 31, 1995, 96 patients (61.2%) had died and 13 (8.3%) were unavailable for follow up. Mean age of the patients was 79.2 yrs and mean duration of LTOT was 2.81 yrs. The mean FEV1 was 0.80 L and mean FEV1/FVC was 48%. The overall survival was poor and 5-yr survival was 21.6% (median survival: 3.01 yrs). Among the variables tested by univariate analysis, factors associated with poor outcome were as follows: %IBW < or = 85 (HR = 2.15, p < 0.001), serum albumin (g/dl) < or = 3.5 (1.81, p < 0.01), hemoglobin (g/dl) < or = 11.0 (1.86, p < 0.01), FEV1/FVC > 50% (0.63, p < 0.05), and high dyspnea ranking (grade 4 or 5) (1.74, p < 0.05). The coexistence of bronchiectasis (3.96, p < 0.01) and malignancy (1.85, p < 0.01) also contributed to poor outcome. Multivariate analysis showed that independent prognostic factors influencing outcome included: nutritional status (%IBW) (HR = 2.08, p < 0.01), dyspnea ranking (2.04, p < 0.01), coexistence of malignancy (2.02, p < 0.01), and FEV1/FVC (0.52, p < 0.01). We conclude that the outcome in elderly COPD patients receiving LTOT is poor, and that outcome is independently influenced by four major factors: malnutrition, severity of dyspnea, coexistence of malignancy, and airflow obstruction.

Characterization of vitamin B12 compounds from edible shellfish, clam, oyster, and mussel.

Vitamin B12 content of various edible shellfish was determined by both Lactobacillus leichmannii ATCC 7830 microbiological and intrinsic factor-chemiluminescence methods. The values determined by the microbiological method were 1.2-19.8 (M/C ratio) fold greater in the shellfish than the values determined by the chemiluminescence method. Vitamin B12 compounds were purified from most eaten shellfish, oyster (M/C, 1.5), mussel (M/C, 1.2), and short-necked clam (M/C, 2.7), and partially characterized. TLC and HPLC patterns of each red-colored vitamin B12 compound (M/C, 1.0-1.2) purified from these shellfish were identical to those of authentic vitamin B12. Although the higher values in the determination of vitamin B12 by the microbiological method may be due to the occurrence of vitamin B12-substitutive compounds, the edible shellfish would be excellent vitamin B12 sources judging from the values (> or = 6 micrograms/100 g) determined by the chemiluminescence method.

Interferon-associated retinopathy in a uniform regimen of natural interferon-alpha therapy for chronic hepatitis C.

BACKGROUND/AIMS: The development of retinal lesions induced by a uniform regimen of interferon-alpha therapy for chronic hepatitis C was prospectively investigated. METHODS: Eighty-one patients received 6 mega units of natural interferon-alpha intramuscularly daily for 2 weeks and then 3 times a week for 22 weeks. The total dose of interferon-alpha administered was uniformly 478 mega units per patient. Two expert ophthalmologists prospectively examined the patients for retinal lesions before, during and after the therapy. RESULTS: Retinopathy was not found in comparison groups or any of the patients before treatment. In total 34.6% (28/81) of the patients showed cotton-wool spots or minor retinal hemorrhage, or both lesions, during therapy, but these lesions were reversed during or after interferon therapy. The occurrence rates of cotton-wool spots alone, retinal hemorrhage alone and both lesions were 13.6% (11/81), 6.2% (5/81), and 14.8% (12/81), respectively. The appearance of retinopathy did not correlate with patients' background including viral loads and response to the therapy, but was more frequently found in older patients and patients with hypertension and/or diabetes mellitus; disappearance of retinopathy was more prolonged than in patients without these complications. Almost all the lesions appeared 2-4 months after the start of the therapy, and the severity of the lesions did not differ between patients with and without hypertension and/or diabetes mellitus. CONCLUSION: Although it is not clear if interferon-associated retinopathy occurs in a dose-dependent manner, the present study shows a standard pattern of the occurrence of retinopathy in patients with chronic hepatitis C receiving a uniform dosage of natural interferon-alpha.

Posterior synechia of the iris after combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation.

PURPOSE: Combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation has become a widely accepted treatment for cataracts in patients with vitreoretinal diseases. We examined factors influencing the development of posterior synechia after this triple procedure. METHODS: One hundred and three patients (107 eyes) were evaluated. The frequency of postoperative posterior synechia, the preoperative diagnosis, whether gas tamponade was used, and the type of lens implanted were reviewed. RESULTS: Twenty-one eyes (19.6%) developed posterior synechia, and the highest rate (12/39 eyes, 30.8%) was in patients with proliferative diabetic retinopathy. Posterior synechia was more frequent after gas tamponade (28.1%) than in eyes without tamponade (10.1%). In proliferative diabetic retinopathy (PDR) patients, fibrin deposition and the amount of retinal photocoagulation were causative factors for posterior synechia. CONCLUSIONS: Factors promoting postoperative synechia after the triple procedure included (1) the existence of PDR, (2) expanding gas tamponade, (3) fibrin deposition in PDR, and (4) the amount of photocoagulation in PDR.

[Two elderly patients with sarcoidosis and Sjögren's syndrome].

Two elderly patients with sarcoidosis complicated with Sjögren's syndrome are described. Case 1: A 70-year-old woman was admitted due to dry eyes. Histological examination of a minor salivary gland specimen revealed lymphocytic infiltration, which was compatible with Sjögren's syndrome. Because uveitis was demonstrated, transbronchial lung biopsy (TBLB) was performed, to confirm a diagnosis of lung sarcoidosis. Histological examination of TBLB showed non-caseating granulomas compatible with sarcoidosis. Case 2: A 70-year-old woman was admitted due to dyspnea on exercise and blurred vision. Two years previously, Sjögren's syndrome was diagnosed because of a positive Shirmer test and positive SS-A antibody. Result of ophthalmic examination were compatible with uveitis. Histological examination of TBLB showed non-caseating granulomas compatible with sarcoidosis. Certain similarities between sarcoidosis and Sjögren's syndrome in terms of immunological aspects have attracted attention. In the present manuscript, a possible relationship between the two diseases as well as the characteristics of elderly sarcoidosis are discussed.

Progressive outer retinal necrosis in a patient with nephrotic syndrome.

Progressive outer retinal necrosis syndrome (PORN) is a variant of necrotizing herpetic retinopathy and the majority of the described cases were related to acquired immunodeficiency syndrome. We present a patient who is HIV negative with nephrotic syndrome and prednisolone use for 4 months who showed clinical features of PORN. Low CD4 counts and lymphocytopenia suggested immunosuppression. In the left eye, tractional retinal detachment at the posterior pole followed by incomplete posterior vitreous detachment developed. In addition to intravenous administration of acyclovir, vitreous surgeries including stripping of the posterior hyaloid and silicone-oil tamponade were successfully performed to repair the retinal detachment in the left eye and to prevent it in the right eye.

[Cavernostomy and simultaneous removal of fungus ball of pulmonary aspergilloma].

Between 1991 and 2000, 21 patients (16 male and 5 female) underwent 28 cavernostomies for the treatment of pulmonary aspergilloma. The median age was 59.4 years (range 37-85 years). The mean %VC was 59.6 (range 30.4-91.2), and the mean FEV 1.0 was 1.51 ml (range 0.64-2.67 ml). The mean body mass index was 17.6 (range 12.7-23.2). The most common complaint was hemoptysis. The underlying lung disease was tuberculosis in 17 cases, atypical mycobacteriosis in 2, and unclassified in 2. All cases had been diagnosed as complex aspergilloma. The mean surgical duration was 136 minutes (range 85-203 min.) and the mean blood loss during surgery was 242 ml(range 5-810 ml). No death or major complications occurred in the postoperative course. During follow-up, 4 patients died of massive hemoptysis, cancer, respiratory failure or an unknown cause. Relapses of aspergilloma occurred in 9 patients (42.9%). Recavernostomy was performed safely on 5 patients. In conclusion, although the relapse rate of aspergilloma was high after cavernostomy, safe reoperations were performed. Cavernostomy is thus an effective treatment in high-risk patients.

Microcirculation in the macular area of eyes with an idiopathic epiretinal membrane.

PURPOSE: To measure the microcirculation in the macula area of eyes before and after the removal of an idiopathic epiretinal membrane (ERM) by vitreous surgery. METHODS: Tissue blood flow in the macula was examined with the Heidelberg retina flowmeter in 12 eyes with an ERM before and 3, 6, and 12 months after vitrectomy. Blood flow measurements were performed in a 10 x 5 degree area in the macula that was divided into superior and inferior areas. At least three measurements were obtained, and the mean blood flow (MBF) was calculated by scanning laser Doppler flowmetry. The ratio of the MBF in the affected eye to that in the fellow eye was used for statistical analysis. RESULTS: The ratios of the MBF in the affected to the fellow eye in the superior area before and 1, 3, 6, and 12 months after surgery were 0.73, 0.51, 0.77, 0.88, and 1.01, respectively. The ratios of the MBF in the inferior area for the same periods were 0.70, 0.52, 0.75, 0.83, and 0.98, respectively. CONCLUSIONS: Eyes with an ERM showed abnormal hemodynamics in the macula that gradually improved after vitrectomy to a status comparable with the MBF of the normal fellow eye.

A new method for quantification of metamorphopsia in patients with epiretinal membrane.

PURPOSE: A new method for quantification of metamorphopsia was applied to study distorted vision in patients with epiretinal membrane. METHOD: Sixty-three patients with unilateral epiretinal membrane in the macula were examined. A modified Amsler chart (a grid of black lines on a white background measuring 12 x 12 cm with grid squares of 2 x 2 cm) was prepared. If patients saw any of the grid lines as irregular or curved, they were asked to trace these on the chart. The length of all lines drawn by the patients was measured, except those on the outer border. The length of the grid is 1200 mm, but it should be drawn longer by patients with metamorphopsia. The severity of metamorphopsia was also scored subjectively and the relationship of grid length to the subjective score and the visual acuity was analyzed. RESULTS: The grid length ranged from 1200 to 1259 mm (mean = 1223.3 mm) and was correlated significantly with the subjective score (P <.01, rho =.387). CONCLUSION: This method might be applicable for evaluating the severity of metamorphopsia and the surgical outcome in patients with epiretinal membrane.

A new method for quantification of metamorphopsia in patients with epiretinal membrane

Purpose: We have developed a new method for quantification of metamorphopsia and applied it to study distorted vision resulting from epiretinal membrane (ERM).Patients and Methods: We prepared a modified Amsler chart, which was a square grid formed by black lines on a white background with 12 cm on a side and divided into 2-cm quadrants. The patients were asked to trace any straight lines on the chart which appeared irregular or curved. The length of all lines traced by the patients was measured except for the outer frame. The total length of the chart itself was 1.200 mm, but it would appear longer in patients with metamorphopsia. In addition, the severity of metamorphopsia was scored subjectively as follows: 1, absent; 2, slight; 3, mild; 4, moderate; and 5, severe. The relationship of the length to the score and to the visual acuity were analysed. Sixty-three patients with unilateral ERM were examined.Results: The length of the line ranged from 1,200 to 1,259 mm (mean 1,223.3 mm) and was correlated significantly to the score. Conclusions: This method might be applied usefully in evaluating the severity of metamorphopsia and the surgical outcome of eyes with ERM.

[Effects of inhaled corticosteroid in elderly patients with chronic obstructive pulmonary disease].

We examined the efficacy of inhaled corticosteroid (beclomethazone dipropionate: BDP) in elderly patients with chronic obstructive pulmonary disease (COPD). Eighty-six patients with COPD were divided into 3 groups: COPD treated without BDP (group 1, n = 26), COPD treated with BDP (group 2, n = 25), and BDP-treated COPD with asthmatic symptoms (group 3, n = 35). Pulmonary function test findings, symptoms, and prognosis for the 3 groups were retrospectively compared. No significant differences in yearly decline of FEV1.0 were observed. Of the patients treated with inhaled corticosteroid (groups 2 and 3), 30% exhibited improved FEV1.0. Of these patients, monthly decline of FEV1.0 correlated negatively with bronchial reversibility in FEV1.0 before and after inhalation of salbutamol (delta FEV1.0) (r = -0.28, p = 0.03). Cough and sputum scores were significantly improved in groups 2 and 3 (p < 0.01). Fewer admissions and episodes of acute exacerbation were noted in groups 2 and 3 than in group 1. From these results, we concluded that inhaled corticosteroid was effective in elderly COPD patients with bronchial reversibility and airway symptoms.

Characterization of a vitamin B12 compound in the edible purple laver, Porphyra yezoensis.

The edible purple laver, Porphyra yezoensis, contained 51.49+/-1.51 microg of vitamin B12 compounds per 100 g dry weight of the laver (mean +/- SEM, n = 4). A vitamin B12 compound was purified from the lyophilized purple laver and partially characterized. The silica gel 60 TLC and reversed-phase HPLC patterns of the purified pink-colored compound were identical to those of authentic vitamin B12, but not to those of vitamin B12 analogues inactive for humans.