MENS-associated increase of muscular protein content via modulation of caveolin-3 and TRIM72.

Microcurrent electrical neuromuscular stimulation (MENS) is known as an extracellular stimulus for the regeneration of injured skeletal muscle in sports medicine. However, the effects of MENS-associated increase in muscle protein content are not fully clarified. The purpose of this study was to investigate the effects of MENS on the muscular protein content, intracellular signals, and the expression level of caveolin-3 (Cav-3), tripartite motif-containing 72 (TRIM72) and MM isoenzyme of creatine kinase (CK-MM) in skeletal muscle using cell culture system. C2C12 myotubes on the 7th day of differentiation phase were treated with MENS (intensity: 10-20 microA, frequency: 0.3 Hz, pulse width: 250 ms, stimulation time: 15-120 min). MENS-associated increase in the protein content of myotubes was observed, compared to the untreated control level. MENS upregulated the expression of Cav-3, TRIM72, and CK-MM in myotubes. A transient increase in phosphorylation level of Akt was also observed. However, MENS had no effect on the phosphorylation level of p42/44 extracellular signal-regulated kinase-1/2 and 5'AMP-activated protein kinase. MENS may increase muscle protein content accompanied with a transient activation of Akt and the upregulation of Cav-3 and TRIM72.

Delta 9-tetrahydrocannabinol-induced catalepsy-like immobilization is mediated by decreased 5-HT neurotransmission in the nucleus accumbens due to the action of glutamate-containing neurons.

Delta(9)-tetrahydrocannabinol (THC) has been reported to induce catalepsy-like immobilization, but the mechanism underlying this effect remains unclear. In the present study, in order to fully understand the neural circuits involved, we determined the brain sites involved in the immobilization effect in rats. THC dose-dependently induced catalepsy-like immobilization. THC-induced catalepsy-like immobilization is mechanistically different from that induced by haloperidol (HPD), because unlike HPD-induced catalepsy, animals with THC-induced catalepsy became normal again following sound and air-puff stimuli. THC-induced catalepsy was reversed by SR141716, a selective cannabinoid CB(1) receptor antagonist. Moreover, THC-induced catalepsy was abolished by lesions in the nucleus accumbens (NAc) and central amygdala (ACE) regions. On the other hand, HPD-induced catalepsy was suppressed by lesions in the caudate putamen (CP), substantia nigra (SN), globus pallidus (GP), ACE and lateral hypothalamus (LH) regions. Bilateral microinjection of THC into the NAc region induced catalepsy-like immobilization. This THC-induced catalepsy was inhibited by serotonergic drugs such as 5-hydroxy-L-tryptophan (5-HTP), a 5-HT precursor, and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a 5-HT receptor agonist, as well as by anti-glutamatergic drugs such as MK-801 and amantadine, an N-methyl-d-aspartate (NMDA) receptor antagonist. THC significantly decreased 5-HT and glutamate release in the NAc, as shown by in vivo microdialysis. SR141716 reversed and MK-801 inhibited this decrease in 5-HT and glutamate release. These findings suggest that the THC-induced catalepsy is mechanistically different from HPD-induced catalepsy and that the catalepsy-like immobilization induced by THC is mediated by decreased 5-HT neurotransmission in the nucleus accumbens due to the action of glutamate-containing neurons.

Pioglitazone opposes neurogenic vascular dysfunction associated with chronic hyperinsulinaemia.

BACKGROUND AND PURPOSE: We previously demonstrated that chronic hyperinsulinaemia induced by drinking high levels of fructose augments adrenergic nerve-mediated vasoconstriction and suppresses vasodilatation mediated by calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. In this study, the effects of pioglitazone on vascular responses induced by stimulation of adrenergic nerves, CGRPergic nerves and vasoactive agents were investigated in pithed rats given 15% fructose solution to drink (FDR). EXPERIMENTAL APPROACH: To assess the effect of pioglitazone on the altered vascular responsiveness in the hyperinsulinaemic state in vivo, changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin II and CGRP were evaluated in pithed control rats and FDR either untreated or treated with pioglitazone. KEY RESULTS: In the pithed FDR, vasoconstrictor responses to SCS and to injections of noradrenaline and angiotensin II were significantly greater than those of pithed control rats. In pithed FDR with artificially increased blood pressure and blockade of the autonomic ganglia, the vasodilator responses to SCS and CGRP injection were significantly smaller than those of pithed control rats. Oral administration of pioglitazone to FDR for two weeks markedly decreased plasma levels of insulin, triglycerides and blood glucose. In FDR pioglitazone diminished the augmented vasoconstrictor responses to SCS, noradrenaline and angiotensin II, and ameliorated the decrease in vasodilator responses to SCS. CONCLUSIONS AND IMPLICATIONS: The present results suggest that pioglitazone improves not only insulin resistance, but also the dysfunctions in vascular control regulated by adrenergic and CGRPergic nerves in the hyperinsulinaemic state.

Relationship between oral mucositis and high-dose methotrexate therapy in pediatric acute lymphoblastic leukemia.

OBJECTIVE: Oral mucositis is a major toxicity in the high-dose methotrexate (HD-MTX) treatment for children with acute lymphoblastic leukemia (ALL). The first aim of this study was to evaluate the relationship between the MTX serum concentration and occurrence of oral mucositis in pediatric ALL patients. The second aim was to clarify the relationship between MTX exposure and epidermal keratinocyte cell injury using an in vitro study. METHODS: 49 patients were treated according to the Japan Association of Childhood Leukemia Study (JACLS) ALL-HR02 protocol. This protocol involves HD-MTX treatment (3 g/m2 for 24-h i.v. infusion). The MTX serum concentrations were measured by a fluorescence polarization immunoassay. The relationship between oral mucositis and MTX serum concentrations 48 and 72 h after administration was determined. The cell toxicity of MTX for human epidermal keratinocytes was analyzed by using a cell viability assay (WST-1 assay). In addition, pharmacokinetic evaluation for clearance, AUC extrapolated from 48 h to infinity (AUC48h-inf) and elimination half-life (t1/2b) were done using the 1-compartmental models. RESULTS: Oral mucositis occurred in 24 patients (49.0%), in whom 20 patients (83.3% in oral mucositis group) showed WHO severity Grade 1 or 2. Only 4 patients (16.7% in oral mucositis group) showed Grade 3 severity. 22 patients (44.9%) had oral mucositis in the group with a concentration under 10-6 M 48 h after MTX administration. There was no significant deference among the cell viabilities in the concentrations of 10-6 M, 10-5 M and 10-4 M 48 h after the MTX exposure. However, the cell viability obtained 24 h after the MTX exposure was significantly different from the respective cell viability 48, 72 and 96 h after the MTX exposure. In the group with oral mucositis, the clearance decreased significantly (p = 0.042), and the t1/2b (p = 0.025) and AUC48h- yen (p = 0.025) increased significantly compared with the non-symptom group. CONCLUSIONS: It seems that there is no significant relationship between the serum MTX concentration and oral mucositis. This in vitro study has demonstrated that the cell injury was related to the duration of MTX exposure rather than a high MTX concentration.

Lactate increases myotube diameter via activation of MEK/ERK pathway in C2C12 cells.

AIM: Lactate is produced in and released from skeletal muscle cells. Lactate receptor, G-protein-coupled receptor 81 (GPR81), is expressed in skeletal muscle cells. However, a physiological role of extracellular lactate on skeletal muscle is not fully clarified. The purpose of this study was to investigate extracellular lactate-associated morphological changes and intracellular signals in C2C12 skeletal muscle cells. METHODS: Mouse myoblast C2C12 cells were differentiated for 5 days to form myotubes. Sodium lactate (lactate) or GPR81 agonist, 3,5-dihydroxybenzoic acid (3,5-DHBA), was administered to the differentiation medium. RESULTS: Lactate administration increased the diameter of C2C12 myotubes in a dose-dependent manner. Administration of 3,5-DHBA also increased myotube diameter. Not only lactate but also 3,5-DHBA upregulated the phosphorylation level of mitogen-activated protein kinase kinase 1/2 (MEK1/2), p42/44 extracellular signal-regulated kinase-1/2 (ERK1/2) and p90 ribosomal S6 kinase (p90RSK). MEK inhibitor U0126 depressed the phosphorylation of ERK-p90RSK and increase in myotube diameter induced by lactate. On the other hand, both lactate and 3,5-DHBA failed to induce significant responses in the phosphorylation level of Akt, mammalian target of rapamycin, p70 S6 kinase and protein degradation-related signals. CONCLUSION: These observations suggest that lactate-associated increase in the diameter of C2C12 myotubes is induced via activation of GRP81-mediated MEK/ERK pathway. Extracellular lactate might have a positive effect on skeletal muscle size.

Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver.

Heme oxygenase is a heme-oxidizing enzyme which generates biliverdin and carbon monoxide (CO). The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation. Microvasculature of the isolated perfused rat liver was visualized by dual-color digital microfluorography to alternately monitor sinusoidal lining and fat-storing Ito cells. In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min per gram of liver. Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 microM) eliminated the baseline CO generation, and the vascular resistance exhibited a 30% elevation concurrent with discrete patterns of constriction in sinusoids and reduction of the sinusoidal perfusion velocity. The major sites of the constriction corresponded to local sinusoidal segments colocalized with Ito cell which were identified by imaging their vitamin A autofluorescence. The increase in the vascular resistance and sinusoidal constriction were attenuated significantly by adding CO (1 microM) or a cGMP analogue 8-bromo-cGMP (1 microM) in the perfusate. From these findings, we propose that CO can function as an endogenous modulator of hepatic sinusoidal perfusion through a relaxing mechanism involving Ito cells.

Heat shock transcription factor 1-associated expression of slow myosin heavy chain in mouse soleus muscle in response to unloading with or without reloading.

AIM: The effects of heat shock transcription factor 1 (HSF1) deficiency on the fibre type composition and the expression level of nuclear factor of activated T cells (NFAT) family members (NFATc1, NFATc2, NFATc3 and NFATc4), phosphorylated glycogen synthase kinase 3α (p-GSK3α) and p-GSK3ß, microRNA-208b (miR-208b), miR-499 and slow myosin heavy chain (MyHC) mRNAs (Myh7 and Myh7b) of antigravitational soleus muscle in response to unloading with or without reloading were investigated. METHODS: HSF1-null and wild-type mice were subjected to continuous 2-week hindlimb suspension followed by 2- or 4-week ambulation recovery. RESULTS: In wild-type mice, the relative population of slow type I fibres, the expression level of NFATc2, p-GSK3 (α and ß), miR-208b, miR-499 and slow MyHC mRNAs (Myh7 and Myh7b) were all decreased with hindlimb suspension, but recovered after it. Significant interactions between train and time (the relative population of slow type I fibres; P = 0.01, the expression level of NFATc2; P = 0.001, p-GSKß; P = 0.009, miR-208b; P = 0.002, miR-499; P = 0.04) suggested that these responses were suppressed in HSF1-null mice. CONCLUSION: HSF1 may be a molecule in the regulation of the expression of slow MyHC as well as miR-208b, miR-499, NFATc2 and p-GSK3 (α and ß) in mouse soleus muscle.

Electric charge distribution in proteins and ionic strength dependence of reaction rate.

The ionic strength dependence of the reaction rate between protein and dichloride anion radical has been investigated by flash photolysis of aqueous chloride-containing lysozyme, ribonuclease A, or insulin. The rate constant for the reaction of lysozyme or ribonuclease A with dichloride anion radicals decreases with increasing ionic strength, while it increases for insulin. The dependence was found to obey an equation derived from the theory of Debye and Hückel or the equation of Wherland and Gray for lysozyme within experimental errors. For ribonuclease A, however, it deviates largely from these equations. In the case of insulin a moderate deviation was observed. The different behavior in the ionic strength dependence is discussed in terms of the electric charge distribution in the protein molecules.

Resonance Raman study on mutant cytochrome P-450 obtained by site-directed mutagenesis.

Resonance Raman spectra were observed for the threonine-301 to serine or valine mutant as well as the wild type of rabbit liver microsomal cytochrome P-450 [laurate(omega-1)-hydroxylase] (P-450(omega-1], which were prepared through site-directed mutagenesis. The high-spin marker resonance Raman (RR) bands became similarly stronger for all the P-450s examined in the oxidized form upon addition of laurate, and the RR spectra in the higher frequency region of the oxidized, reduced and CO-adduct forms did not distinctly differ among the P-450s examined. Nevertheless, the Fe-CO stretching mode (vFe-CO) of the CO adduct exhibited an upshift for the valine mutant, suggesting positional proximity of Thr-301 to bound CO like Thr-252 of P-450cam, in agreement with the expectation from the sequence analysis. The vFe-CO band was shifted to higher frequency upon binding of normal alkyl fatty acids with C10 or longer alkyl chain but little affected by binding of shorter fatty acids.

Hydrogen bonding interaction of the amide group of Asn and Gln at distal E7 of bovine myoglobin with bound-ligand and its functional consequences.

Asn and Gln with an amide group at gamma- and delta-positions, respectively, were substituted for distal His-E7 of bovine myoglobin to establish a system where hydrogen bonding interaction between the distal residue and bound-ligand can be altered by changing donor-acceptor distance. Two mutant myoglobins showed nearly identical (1)H-NMR spectral pattern for resolved heme peripheral side-chain and amino acid proton signals and similar two-dimensional NMR connectivities irrespective of cyanide-bound and -unbound states, indicating that the heme electronic structure and the molecular structure of the active site are not affected by a difference in one methylene group at the E7 position. Chemical exchange rate of Asn-E7 N(delta)H proton in met-cyano myoglobin is larger than that of Gln-E7 N(epsilon)H proton by at least two orders of magnitude, suggesting a considerable difference in the strength of hydrogen bond between the E7 side-chain and bound-ligand, due to the differential donor-acceptor distance between the two mutants. Thus a comparative study between the two proteins provides an ideal system to delineate a relationship between the stabilization of bound-ligand by the hydrogen bond and myoglobin's ligand affinity. The Asn-mutant showed a faster dissociation of cyano ion from met-myoglobin than the Gln-mutant by over 30-fold. Similarly, oxygen dissociation is faster in the Asn-mutant than in the Gln-mutant by approximately 100-fold. Association of cyanide anion to the mutant met-myoglobin was accelerated by changing Gln to Asn by a 4-fold. Likewise, oxygen binding was accelerated by approximately 2-fold by the above substitution. The present findings confirm that hydrogen bonding with the distal residue is a dominant factor for determining the ligand dissociation rate, whereas steric hindrance exerted by the distal residue is a primary determinant for the ligand association.

Deficiency of heat shock transcription factor 1 suppresses heat stress-associated increase in slow soleus muscle mass of mice.

AIM: Effects of heat shock transcription factor 1 (HSF1) deficiency on heat stress-associated increase in slow soleus muscle mass of mice were investigated. METHODS: Both HSF1-null and wild-type mice were randomly assigned to control and heat-stressed groups. Mice in heat-stressed group were exposed to heat stress (41 °C for 60 min) in an incubator without anaesthesia. RESULTS: Significant increase in wet and dry weights, and protein content of soleus muscle in wild-type mice was observed seven days after the application of the heat stress. However, heat stress had no impact on soleus muscle mass in HSF1-null mice. Neither type of mice exhibited much effect of heat stress on HSF mRNA expression (HSF1, HSF2 and HSF4). On the other hand, heat stress upregulated heat shock proteins (HSPs) at the mRNA (HSP72) and protein (HSP72 and HSP110) levels in wild-type mice, but not in HSF1-null mice. The population of Pax7-positive nuclei relative to total myonuclei of soleus muscle in wild-type mice was significantly increased by heat stress, but not in HSF1-null mice. Furthermore, the absence of HSF1 gene suppressed heat stress-associated phosphorylation of Akt and p70 S6 kinase (p-p70S6K) in soleus muscle. CONCLUSION: Heat stress-associated increase in skeletal muscle mass may be induced by HSF1 and/or HSF1-mediated stress response that activates muscle satellite cells and Akt/p70S6K signalling pathway.

Observation of the FeIV=O stretching Raman band for a thiolate-ligated heme protein. Compound I of chloroperoxidase.

The FeIV=O stretching vibration has never been identified for a cysteine-coordinated heme enzyme. In this study, resonance Raman and visible absorption spectra were observed simultaneously for transient species in the catalytic reaction of chloroperoxidase with hydrogen peroxide by using our original apparatus for mixed-flow and Raman/absorption simultaneous measurements. For the first intermediate, the FeIV=O stretching Raman band was observed at 790 cm-1, which shifted to 756 cm-1 with the 18O derivative, but the v4 band was too weak to be identified. This suggested the formation of an oxoferryl porphyrin pi cation radical. The second intermediate gave an intense v4 band at 1,372 cm-1 but no oxygen isotope-sensitive Raman band, suggesting oxygen exchange with bulk water.

Affinity separation of human plasma gelsolin on Affi-Gel Blue.

Human plasma gelsolin was specifically eluted with 1 mM adenosine 5'-triphosphate from an Affi-Gel Blue column. Since the ionic strength of sodium chloride required to elute the protein from the dye column was much higher than that of 1 mM adenosine 5'-triphosphate, the binding of plasma gelsolin with the dye-ligand appeared to be biospecific. Taking advantage of this affinity interaction, we have developed a revised purification method of human plasma gelsolin. The purification included ammonium sulfate precipitation, diethylaminoethyl-Sepharose chromatography, Affi-Gel Blue chromatography, and Phenyl-Sepharose chromatography. The method allowed a reproducible purification of the protein to apparent homogeneity, producing a 331-fold purification with a yield of 6%.

X-ray crystal structure and catalytic properties of Thr252Ile mutant of cytochrome P450cam: roles of Thr252 and water in the active center.

The structure-function relationship in cytochrome P450cam monooxygenase was studied by employing its active site mutant Thr252Ile. X-ray crystallographic analyses of the ferric d-camphor-bound form of the mutant revealed that the mutation caused a structural change in the active site giving an enlarged oxygen-binding pocket that did not contain any hydrophilic group such as the OH group of Thr and H(2)O. The enzyme showed a low monooxygenase activity of ca. 1/10 of the activity of the wild-type enzyme. Kinetic analyses of each catalytic step revealed that the rate of proton-coupled reduction of the oxygenated intermediate of the enzyme, a ternary complex of dioxygen and d-camphor with the ferrous enzyme, decreased to about 1/30 of that of the wild-type enzyme, while the rates of other catalytic steps including the reduction of the ferric d-camphor-bound form by reduced putidaredoxin did not change significantly. These results indicated that a hydrophilic group(s) such as water and/or hydroxyl group in the active site is prerequisite to a proton supply for the reduction of the oxygenated intermediate, thereby giving support for the operation of a proton transfer network composed of Thr252, Asp251, and two other amino acids and water proposed by previous investigators.

Ameliorative effect of vasopressin-(4-9) through vasopressin V(1A) receptor on scopolamine-induced impairments of rat spatial memory in the eight-arm radial maze.

In order to clarify the mechanism by which pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH(2) (vasopressin-(4-9)), a major metabolite C-terminal fragment of [Arg(8)]-vasopressin (vasopressin-(1-9)), improves learning and memory, we used several different drugs such as an acetylcholine receptor antagonist, a Ca(2+)/calmodulin-dependent protein kinase II inhibitor, vasopressin receptor antagonists and L-type Ca(2+) channel blocker to disrupt spatial memory in rats. Moreover, we examined the effect of vasopressin-(4-9) on acetylcholine release in the ventral hippocampus using microdialysis. Vasopressin-(4-9) (10 fg/brain, i.c.v.) improved the impairment of spatial memory in the eight-arm radial maze induced by scopolamine, pirenzepine and Ca(2+)/calmodulin -dependent protein kinase II inhibitor. Pirenzepine, a vasopressin V(1A) receptor antagonist, and L-type Ca(2+) channel blocker, but not a vasopressin V(2) receptor antagonist, suppressed the effects of vasopressin-(4-9) on scopolamine-induced impairment of spatial memory. Moreover, vasopressin-(4-9) did not affect acetylcholine release in the ventral hippocampus of intact rats or of scopolamine-treated rats as assessed by microdialysis. These results suggest that vasopressin-(4-9) activates vasopressin V(1A) receptors on the postsynaptic membrane of cholinergic neurons, and induces a transient influx of intracellular Ca(2+) through L-type Ca(2+) channels to interact with muscarinic M(1) receptors. The activation of these processes by vasopressin-(4-9) is critically involved in the positive effect of vasopressin-(4-9) on scopolamine-induced impairment of spatial memory.

Vitamin D-binding protein synthesized by a human hepatocellular carcinoma cell line.

The binding protein for 25-hydroxycholecalciferol was studied in the medium spent for the culture of HuH-7 cells, which were originally derived from a human hepatocellular carcinoma tissue. The binding protein for 25-hydroxycholecalciferol synthesized by HuH-7 cells was immunologically similar to vitamin D-binding protein in human serum and had an inter-alpha mobility. A sedimentation coefficient of 4.1 S was found on sucrose density gradient analyses. The molecular weight was estimated to be approximately 58,000 by gel filtration on a standardized column of Sephadex G-150. When mixed with filamentous actin purified from rabbit skeletal muscle, it depolymerized filamentous actin and bound to monomeric, globular actin to make a 5.5 S 1:1 molar complex with a molecular weight of approximately 100,000. These results support the conclusion that HuH-7 cells produce a functional vitamin D-binding protein.

Partial purification and characterization of human hepatoma-derived growth factor.

A human hepatoma cell line, HuH-7, which was established from a hepatoma tissue removed at surgical operation from an adult Japanese male, grows autonomously in a serum-free chemically defined medium. A human hepatoma-derived growth factor with potent growth-promoting activity, was partially purified from the conditioned medium of HuH-7 cells, using ion-exchange, heparin affinity chromatography and gel filtration. The partially purified growth factor (HuHGF) is acid- and heat-labile, and sensitive to reduction and trypsin digestion. HuHGF, which is of relatively high molecular weight (about 64 kDa) examined by gel filtration, stimulates not only the DNA synthesis of Swiss mouse 3T3 fibroblasts, but also the growth of HuH-7 cells in serum-free chemically defined medium, suggesting that it is produced by and acts on HuH-7 cells as an autocrine growth factor. This putative growth factor may play an important role in the autonomous growth of hepatoma and may lead to useful diagnostic or therapeutic approaches to human hepatoma.

Docetaxel enhances the cytotoxicity of tetrahydropyranyladriamycin in a sequence-dependent manner.

BACKGROUND: Taxanes and anthracyclines are active against breast cancer. In this study we investigated the combined antitumor activity of these drugs, with particular regard to sequence-dependency. MATERIALS AND METHODS: The combined antitumor activity of docetaxel and tetrahydropyranyladriamycin (THP) against two human breast cancer xenografts was assessed using an in vitro histoculture drug-response assay. The sequence-dependency of the combined cytotoxicity was evaluated by isobologram. RESULTS: A synergistic antitumor activity of combined docetaxel + THP was exhibited against the R-27 xenograft when docetaxel was given first or simultaneously with THP. However, this synergism was diminished when THP was used before docetaxel. While an additive effect of combined docetaxel + THP was observed against MX-1 xenograft when docetaxel was given first or simultaneously with THP, this effect was not marked using the THP/docetaxel sequence. CONCLUSION: Docetaxel increased the antitumor activity of THP, but only when administered before or simultaneously with THP.

Duplication of the thumb. A retrospective review of two hundred and thirty-seven cases.

Over a twenty-two-year period, 237 patients (261 hands) with duplication of the thumb were seen in the Hand Clinic of Osaka University Hospital. Two groups were identified: Group A, 141 patients without previous surgical treatment, and Group B, ninety-six patients with residual deformity despite previous surgical treatment. Using a modification of Wassel's classification, seven types of deformity were defined. In Group A these types were identified on the basis of the observed duplications of bone and soft tissue. In all but ten of the Group-B patients preoperative roentgenograms were not available and the type of deformity had to be deduced from the residual duplicated bone, the surgical scar, and the residual deformity. Surgery, performed on 193 hands (125 in Group A and sixty-eight in Group B), attempted to restore normal anatomical relationships. The results could be evaluated in 130 hands according to the range of motion, joint stability, and alignment of the remaining thumb after an average follow-up of 35.0 months. According to the rating system described, the results were rated as good in 75.5 per cent, fair in 20.2 per cent, and poor in 4.3 per cent of the ninety-four hands in Group-A patients who were followed. In the thirty-six hands of Group-B patients who could be followed, the preoperative and postoperative scores were compared. Thirteen were not improved while the other twenty-three, sixteen improved from fair to good and seven improved from poor to fair, to give a good result in 63.9 per cent of the Group-B patients who were followed. The results in these 130 Group-A and B hands emphasize the importance of providing muscle balance and, in young patients, of performing an arthroplasty of the interphalangeal or metacarpophalangeal joint when indicated, although arthrodesis was indicated as a salvage operation for Group-B patients who were more than fifteen years old.

Changes in diffusion-weighted MRI after status epilepticus.

A 3-year-old male developed hemiplegia and aphasia after convulsive status epilepticus. Diffusion-weighted magnetic resonance images demonstrated cytotoxic edema in the white matter 6 days after the seizure episode and subsequently in the gray matter after an additional 7 days. Diffusion-weighted magnetic resonance images demonstrated a subacute evolution of the pathologic process after the status epilepticus.