Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival of developing motor neurons in vitro and to rescue motor neurons from axotomy-induced cell death in vivo. In this ...study, we examined the effects of exogenous BDNF on the progression of wobbler mouse motor neuron disease (MND). After clinical diagnosis at age 3 to 4 weeks, 20 affected mice received subcutaneous injections of recombinant human BDNF (5 mg/kg, n = 10) or vehicle (n = 10), three times a week for 4 weeks. In a separate experiment done to conduct a histometric analysis of the C-5 and C-6 ventral roots and to determine the number of myelinated nerve fibers, 7 wobbler mice received identical BDNF treatment. In the 10 BDNF-treated wobbler mice, grip strength declined at a slower rate (p < 0.03) and was twice as great as that of vehicle-treated animals at the end of treatment (p < 0.01). In vivo biceps (p < 0.01) and in vitro muscle twitch tensions (p < 0.02) were also greater than those of vehicle-treated mice. The biceps muscle weight was 20% greater (p < 0.05) and the mean muscle fiber diameter was significantly larger in BDNF-treated mice (p < 0.001) because the number of small (denervated) muscle fibers was markedly reduced. The number of myelinated motor axons at the cervical ventral roots studied in the additional 7 affected mice was 25% greater with BDNF treatment (p < 0.0001). This study establishes that exogenous BDNF administration can retard motor dysfunction in a natural MND and diminish denervation muscle atrophy and motor axon loss.
Phenylketonuria (PKU) is an autosomal recessive genetic disease caused by the defects in the phenylalanine hydroxylase (PAH) gene. Individuals homozygous for defective PAH alleles show elevated ...levels of systemic phenylalanine and should be under strict dietary control to reduce the risk of neuronal damage associated with high levels of plasma phenylalanine. Researchers predict that plant phenylalanine ammonia-lyase (PAL), which converts phenylalanine to nontoxic t-cinnamic acid, will be an effective therapeutic enzyme for the treatment of PKU. The problems of this potential enzyme therapy have been the low stability in the circulation and the antigenicity of the plant enzyme. Recombinant PAL originated from parsley (Petroselinum crispum) chemically conjugated with activated PEG₂ 2,4-bis(O-methoxypolyethyleneglycol)-6-chloro-s-triazine showed greatly enhanced stability in the circulation and was effective in reducing the plasma concentration of phenylalanine in the circulation of mice. PEG-PAL conjugate will be an effective therapeutic enzyme for the treatment of PKU.
Tuberous sclerosis (TSC) is caused by a mutation in either the TSC1 or TSC2 gene. The clinical manifestations of mutations of the two genes are hardly distinguishable, for reasons as yet unknown. In ...this study, we examined the expression of the products of these genes, hamartin and tuberin, in control and TSC tissues. Western blotting disclosed that hamartin and tuberin are both abundant in the cerebral gray matter and that they have similar subcellular distributions and developmental patterns of expression. Immunohistochemical localizations of hamartin and tuberin were also similar, with high levels of expression being localized to the cerebral neurons and glial cells, renal uriniferous and collecting tubules, and cardiac muscles. In the cerebrum with TSC, both hamartin and tuberin were simultaneously reduced in the cortical tubers and subependymal giant cell astrocytomas, and from the normal-appearing cortex. The renal angiomyolipomas and cardiac rhabdomyomas also showed a loss of both the proteins. These results provide evidence for the co-localization and interaction of hamartin and tuberin in vivo, and suggest that a mutation in one TSC gene may secondarily affect the expression of the other in some TSC lesions.
Although balloon dilation is widely used in nonmalignant pyloric stenosis, little information is available on either the short-term or long-term results of this type of therapy in patients with ...obstructive gastroduodenal Crohn's disease.
Five patients with Crohn's disease who had obstructive gastroduodenal lesions were treated using endoscopic balloon dilation.
All the initial dilations successfully provided symptomatic relief. However, three of the five patients developed recurrent obstructive symptoms during a mean follow-up period of 4.2 years. Due to symptomatic recurrence, three patients required successive or regularly scheduled repeat balloon dilations, which were successful without any complications, and all of the patients were able to avoid surgical intervention.
These results suggest that over a prolonged period of time, patients who have undergone balloon dilation for obstructive gastroduodenal Crohn's disease have a high rate of recurrence of symptomatic gastric obstruction. However, repeat dilations are successful in continuing to prevent the need for surgery.
Both Colletotrichum and Magnaporthe spp. develop appressoria pigmented with melanin, which is essential for fungal pathogenicity. 1,8-Dihydroxynaphthalene (1,8-DHN) is believed to be polymerized to ...yield melanin around the appresorial cell wall through the oxidative activity of laccases. However, no 1,8-DHN laccase has yet been identified in either Colletotrichum or Magnaporthe spp. Here, we report a laccase gene, LAC2, that is involved in the appressorial melanization of Colletotrichum orbiculare, which causes cucumber anthracnose. LAC2 encodes a protein with a signal peptide and has high homology to fungal laccases. The conidial color of lac2 mutants is distinct from that of the C. orbiculare wild type, and the mutants are nonpathogenic. Notably, the mutant appressoria are defective in melanization, and a host invasion assay showed that the appressoria are nonfunctional. LAC2 was induced during appressorial melanization. These results suggest that LAC2 oxidizes 1,8-DHN in the appressoria. The LAC2 homologues of other fungi located in the same phylogenetic clade as LAC2 fully complemented the lac2 mutants. Interestingly, a LAC2 homologue, located in a different clade, complemented the conidial pigmentation but not appressorial melanization of the mutants, suggesting that the LAC2 function in appressorial melanization might only be conserved in laccases of the LAC2 clade.
Sevoflurane reacts with soda lime, generating degradation products. The concentrations of sevoflurane degradation products in a low-flow circuit have been reported for anesthesia times of less than 5 ...h. In this study, sevoflurane degradation products generated during low-flow anesthesia exceeding 10 h were examined.
Sixteen patients received sevoflurane anesthesia with a fresh gas flow rate of 11/min. In eight patients, soda lime was used as the CO2 absorbent; in the other eight patients, Baralyme was used. During anesthesia, the concentrations of degradation products in the circuit, the temperature of the CO2 absorbent, inspired and end-tidal sevoflurane concentrations, and the volume of CO2 eliminated by the patient were measured. Gas was sampled from the inspiratory limb of the circuit and analyzed by gas chromatography.
Two degradation products, CF2 = C(CF3)-O-CH2F (compound A) and CH3OCF2CH(CF3)OCH2F (compound B), were detected. In the soda lime group, the individual maximum concentration of compound A was 23.6 +/- 2.9 (12.0-37.4) ppm. In the Baralyme group, the concentration was 32.0 +/- 2.3 (23.5-41.3) ppm. The individual maximum concentration of compound A in the Baralyme group was significant higher than A in the Baralyme group was significant higher than that in the soda lime group. Compound B was detected in two patients, reaching a maximum concentration of 0.2 ppm. The end-tidal sevoflurane concentration, temperature of the CO2 absorbent, and volume of CO2 eliminated by the patient were the same in both groups.
The degradation products detected were at low concentrations in long-duration, low-flow anesthesia with sevoflurane. Baralyme produced higher concentrations of degradation products than soda lime.
We report a recessive mutation of rice,
aberrant panicle organization 1 (
apo1), which severely affects inflorescence architecture, floral organ identity, and leaf production rate. In the wild-type ...inflorescence, the main-axis meristem aborts after forming 10–12 primary branch primordia. However, in
apo1, the main-axis meristem was converted to a spikelet meristem after producing a small number of branch primordia. In addition, the branch meristems in
apo1 became spikelet meristems earlier than in wild type. Therefore, in the inflorescence, the
apo1 mutation caused the precocious conversion of the meristem identity. In the
apo1 flower, lodicules were increased at the expense of stamens, and carpels were formed indeterminately by the loss of meristem determinacy. Vegetative development is also affected in the
apo1. Leaves were formed rapidly throughout the vegetative phase, indicating that
APO1 is also involved in temporal regulation of leaf production. These phenotypes suggest that the
APO1 plays an important role in the temporal regulation of both vegetative and reproductive development.
Amyloid β-protein (Aβ) has been reported to interact with a variety of lipid species, although the thermodynamic driving force remains unclear. We investigated the binding of Aβs labeled with the dye ...diethylaminocoumarin (DAC-Aβs) to lipid bilayers under various conditions. DAC-Aβ-(1–40) electrostatically bound to anionic and cationic lipids at acidic and alkaline interfacial pH, respectively. However, at neutral pH, electroneutral Aβ did not bind to these lipids, indicating little hydrophobic interaction between Aβ-(1–40) and the acyl chains of lipids. In contrast, DAC-Aβ associated with glycolipids even under electroneutral conditions. These results suggested that hydrogen-bonding as well as hydrophobic interactions with sugar groups of glycolipids drive the membrane binding of Aβ-(1–40).
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