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Hiroshi Takashima

Publications and source records attributed to Hiroshi Takashima.

At least 19 recordsLinked to original sources
PubMed2006

Photoinduced intramolecular electron-transfer reactions of reconstituted met- and zinc-myoglobins appending acridine and methylacridinium ion as DNA-binders.

Three types of reconstituted met- and zinc-myoglobin (metMb and ZnMb) dyads, ZnMbAc(4)Me+, ZnMbAc(6)Me+, and metMbAc(6) have been prepared by incorporating chemically modified metalloporphyrin cofactor appending an acridine (Ac) or a methylacridinium ion ([AcMe]+) into apo-Mb. In the bimolecular system between ZnMb and [AcMe]+, the photoexcited triplet state of ZnMb, 3(ZnMb)*, was successfully quenched by [AcMe]+ to form the radical pair of ZnMb cation (ZnMb*+) and reduced methylacridine ([AcMe]*), followed by a thermal back ET reaction. The rate constants for the intermolecular quenching ET (kq) and the back ET reaction (kb) at 25 degrees C were successfully obtained as kq = (8.8 +/- 0.4) x 10(7) M(-1) s(-1) and kb = (1.2 +/- 0.1) x 10(8) M(-1) s(-1), respectively. On the other hand, in case of the intramolecular photoinduced ET reactions of ZnMbAc(4)Me+ and ZnMbAc(6)Me+ dyads, the first-order quenching rate constants (kET) of 3(ZnMb)* by [AcMe]+ moiety were determined to be kET = 2.6 x 10(3) and 2.5 x 10(3) s(-1), respectively. When such ET occurs along the alkyl spacer via through-bond mechanism at the surface of Mb, the obtained kET is reasonable to provide decay constant of beta (1.0-1.3 A(-1)). Upon photoirradiation of [AcMe]+ moiety, kinetic studies also presented the intramolecular quenching reactions from the excited singlet state, 1([AcMe]+)*, whose likely process is the photoinduced energy-transfer reaction. For metMbAc(6) dyad, steady-state fluorescence was almost quenched, while the signal around 440 nm gradually appeared in the presence of various concentrations of DNA. Our study implies that synthetic manipulation at the Mb surface, by using an artificial DNA-binder coupled with photoinduced reaction, may provide valuable information to construct new Mb-DNA complex and sensitive fluorescent for DNA.

Acridines↗
PubMed2006

Molecular mechanism of rigid spine with muscular dystrophy type 1 caused by novel mutations of selenoprotein N gene.

Mutations of selenoprotein N, 1 gene (SEPN1) cause rigid spine with muscular dystrophy type 1 (RSMD1), multiminicore disease, and desmin-related myopathy. We found two novel SEPN1 mutations in two Japanese patients with RSMD1. To clarify the pathomechanism of RSMD1, we performed immunohistochemical studies using a newly developed antibody for selenoprotein N. Selenoprotein N was diffusely distributed in the cytoplasm of the control muscle, but was reduced and irregularly expressed in the cytoplasm of a patient with RSMD1. The expression pattern was very similar to that of calnexin, a transmembrane protein of the endoplasmic reticulum. Selenoprotein N seems to be an endoplasmic reticulum glycoprotein, and loss of this protein leads to disturbance of muscular function. One of the families had the SEPN1 homozygous mutation in the initiation codon 1_2 ins T in exon 1 and showed truncated protein expression. The other had a homozygous 20-base duplication mutation at 80 (80_99dup, frameshift at R27) which, in theory, should generate many nonsense mutations including TGA. These nonsense mutations are premature translation termination codons and they degrade immediately by the process of nonsense-mediated decay (NMD). However, truncated selenoprotein N was also expressed. A possible mechanism behind this observation is that SEPN1 mRNAs may be resistant to NMD. We report on the possible molecular mechanism behind these mutations in SEPN1. Our study clarifies molecular mechanisms of this muscular disorder.

Adult↗
PubMed2006

Association of AKT1 haplotype with the risk of schizophrenia in Iranian population.

AKT-glycogen synthase kinase 3beta (GSK3beta) signaling is a target of lithium and has been implicated in the pathogenesis of mood disorders and schizophrenia. AKT1 protein level is decreased in the peripheral lymphocytes and brains of schizophrenic patients. The SNP2/3/4 TCG haplotype of AKT1 was associated with schizophrenia in patients with Northern European origin. In the present study, we genotyped five single nucleotide polymorphisms (SNP1-5) of AKT1 gene according to the original study in Iranians comprising of 321 schizophrenic patients and 383 controls, all residing in Mashhad city, Northeastern Iran. Haplotype analysis showed that the frequency of a five-SNP haplotype (AGCAG) was significantly higher in schizophrenic patients (0.068) than that of controls (0.034) (P = 0.03 after Bonferroni correction, OR = 2.04, CI = 1.2-3.4). In stratified analysis by schizophrenia subtypes, the frequency of the same haplotype was significantly higher in disorganized subtype (n = 78, frequency of haplotype=0.081) when compared with normal controls (P = 0.04 after Bonferroni correction, OR = 2.59, CI = 1.3-5.2). Our findings did not confirm the association of AKT1 SNP2/3/4 TCG haplotype with the risk of schizophrenia as reported in the original study but showed the evidence of association with a different haplotype, AKT1 five-SNP AGCAG haplotype, with the risk of schizophrenia in Iranian population.

Alleles↗
PubMed2006

Stereoselective and driving-force-dependent photoinduced electron-transfer reactions of zinc myoglobin with optically active N,N'-dimethylcinchoninium and N,N'-dimethylcinchonidinium ions.

In order to understand the detailed mechanism of the stereoselective photoinduced electron-transfer (ET) reactions of zinc-substituted myoglobin (ZnMb) with optically active molecules by flash photolysis, we designed and prepared new optically active agents, such as N,N'-dimethylcinchoninium diiodide ([MCN]I2) and N,N'-dimethylcinchonidinium diiodide ([MCD]I2). The photoexcited triplet state of ZnMb, 3(ZnMb)*, was successfully quenched by [MCN]2+ and [MCD]2+ ions to form the radical pair of ZnMb cation (ZnMb.+) and reduced [MCN].+ and [MCD].+, followed by a thermal back ET reaction to the ground state. The rate constants (kq) for the ET quenching at 25 degrees C were obtained as kq(MCN)=(1.9+/-0.1)x10(6) M-1 s-1 and kq(MCD)=(3.0+/-0.2)x10(6) M-1 s-1, respectively. The ratio of kq(MCD)/kq(MCN)=1.6 indicates that the [MCD]2+ preferentially quenches 3ZnMb)*. The second-order rate constants (kb) for the thermal back ET reaction from [MCN].+ and [MCD].+ to ZnMb.+ at 25 degrees C were kb(MCN)=(0.79+/-0.04)x10(8) M-1 s-1 and kb(MCD)=(1.0+/-0.1)x10(8) M-1 s-1, respectively, and the selectivity was kq(MCD)/kq(MCN)=1.3. Both quenching and thermal back ET reactions are controlled by the ET step. In the quenching reaction, the energy differences of DeltaDeltaH ( not equal)(MCD-MCN) and DeltaDeltaS ( not equal)(MCD-MCN) at 25 degrees C were obtained as -1.1 and 0 kJ mol-1, respectively. On the other hand, DeltaDeltaH (not equal)(MCD-MCN)=11+/-2 kJ mol-1 and TDeltaDeltaS (not equal)(MCD-MCN)=-10+/-2 kJ mol-1 were given in the thermal back ET reaction. The highest stereoselectivity of 1.7 for [MCD].+ found at low temperature (10 degrees C) was due to the DeltaDeltaS ( not equal) value obtained in the thermal back ET reaction.

Cinchona Alkaloids↗
PubMed2006

[Molecular genetics of inherited neuropathies].

Inherited neuropathies are clinically and genetically heterogeneous. At least 28 genes and 12 loci have been associated with Charcot-Marie-Tooth disease (CMT) and related inherited neuropathies. Most causes of inherited neuropathy have been discovered by positional cloning technique and in the past two years, the pace of CMT gene discovery has accelerated. Genetic studies have revealed the following gene mutations as the causes of inherited neuropathies; PMP22, MPZ, EGR2, SOX10, SIMPLE/LITAF, ARHGEF10 for CMT1 (autosomal dominant demyelinating form); GDAP1, MTMR2, SBF2/MTMR13, KIAA1985, NDRG1 PRX for CMT4 (autosomal recessive demyelinating form), MFN2, KIF1B, RAB7, GARS, NEFL, HSPB1, HSPB8 for CMT2 (autosomal dominant axonal form); LMNA, GAN1, KCC3, TDP1, APTX, SETX for AR-CMT2 (autosomal recessive axonal form); GIB1 for CMTX (X-linked CMT); DNM2 for CMT-DI (autosomal dominant CMT with intermediate nerve conduction velocities); and DHH for minifascicular neuropathy. These discovered CMT causing genes/proteins include those which show unpredictable correlations with the peripheral nervous system. However, these genes/proteins are definitely important for the peripheral nerve, and their discovery should pave the way for dramatic progress in the understanding of peripheral nerve biology. On the other hand, genotype-phenotype correlations of these genes are also important in order to understand the pathomechanisms of inherited neuropathy. Because, based on mutation studies, a large number of genes associated with both the CMT1/4 and CMT2 forms have been identified, it is usually difficult to predict the causative gene based on clinical information from patients without specific complications. To clarify the specific features and molecular mechanisms of five diseases that we previously reported, we reviewed recent progress in HMSN-P linked to chromosome 3, CMT4F caused by PRX, CMT4A caused by GDAP1, CMT4B2 caused by SBF2/MTMR13, and SCAN1 caused by TDP1. HMSN-P is characterized by late onset, proximal dominant severe muscle weakness, fasciculations, muscle cramp and sensory involvement. HMSN-P is a primary neuronopathy. Mutations in periaxin are associated with a broad spectrum of demyelinating neuropathies including DSS, a sensory dominant form and early onset slowly progressive CMT. Pathologically, loss of myelinated fibers, demyelination, small onion bulb formations, tomacula formation and myelin foldings were seen in sural nerves. Absence of septate like junction in the paranodal loop suggests that periaxin could be required for the adhesion complex. GDAP1 is a relatively common cause of CMT4. Half of reported patients showed the demyelinating form, while the rest showed the axonal form. The typical feature of CMT4A is paresis of the vocal cords and diaphragm. CMT4B2 is characterized by autosomal recessive, juvenile onset glaucoma and focally folded myelin in sural nerves. SBF2/MTMR13 mutations cause CMT4B2. Early onset glaucoma was seen in patients with nonsense mutations. SBF2/MTMR13 and MTMR2, which is the cause of CMT4B1, could be acting on the same 3-phosphoinositide signaling pathway. Clinical phenotypes of patients with TDP1, APTX, or SETX mutations share common clinical findings, namely cerebellar ataxia and axonal neuropathy. TDP1 and aprataxin both act on the single strand break repair pathway, with TDP1 working specifically on topoisomerase I related SSBR. Senataxin is a RNA helicase acting on RNA maturation and termination in yeast. Since these three proteins share a common pathway, disruption in any of them could induce a delay in the transcription process. The low rate of protein supply could lead to deaths of large neuronal cells.

Adaptor Proteins, Signal Transducing↗
PubMed2005

[Application of sentinel node navigation surgery to prostate cancer].

A sentinel node (SN) validation study using a radioactive tracer and back-up extended pelvic lymph node (LN) dissection was performed in 40 patients with non-metastatic prostate cancer (PCa). The results of the study were favorable, with sensitivity, specificity, and accuracy of SN biopsies revealed 90%, 100%, and 97.5%, respectively. Although 1 patient had false negative LNs, the SN concept was still validated because extensive LN metastasis disrupted the physiological lymphatic flow in this case. Based on our promising results to date, we examined the utility of SN navigation surgery (SNNS) in patients with LN metastasis probability of 10% or less on Partin tables. Endoscopic minilaparotomy surgery, established by Kihara et al., was applied to our SN biopsies in 9 patients with clinically localized PCa. SNs were successfully resected in 7 of these patients. Limited pelvic LN dissection was performed in 3 patients, including 1 patient with LN metastasis. SN biopsy and radical prostatectomy were performed via a 5-cm lower abdominal incision. In summary, endoscopic minilaparotomy SNNS is a less invasive form of radical surgery for PCa that offers accurate diagnosis of LN status.

Endoscopy↗
PubMed2004

Fine mapping of 16q-linked autosomal dominant cerebellar ataxia type III in Japanese families.

The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. To date, at least 11 genes and 13 additional loci have been identified in ADCAs. Despite phenotypic differences, spinocerebellar ataxia 4 (SCA4) and Japanese 16q-linked ADCA type III map to the same region of 16q22.1. We report four Japanese families with pure cerebellar ataxia and a disease locus at 16q22.1. Our families yielded a peak lod score of 6.01 at marker D16S3141. To refine the candidate region, we carried out genetic linkage studies in four pedigrees with a high density set of DNA markers from chromosome 16q22.1. Our linkage data suggest that the disease locus for 16q-ADCA type III is within the 1.25-Mb interval delineated by markers 17msm and CTTT01. We screened for mutations in 36 genes within the critical region. Our critical region lies within the linkage interval reported for SCA4 and for Japanese 16q-ADCA type III. These data suggest that the ADCA that we have characterized is allelic with SCA4 and Japanese 16q-linked ADCA type III.

Alleles↗
PubMed2004

Validity of sentinel lymph node concept for patients with prostate cancer.

PURPOSE: We investigated the feasibility and validity of the sentinel lymph node concept for patients with prostate cancer. MATERIALS AND METHODS: A total of 24 patients (mean age 68.1 years) with prostate cancer but without detectable distant metastases were enrolled in this study. Radioactive tracer (technetium labeled phytate) was injected into the prostate 5 to 6 hours before surgery. Preoperative lymphoscintigraphy was viewed, and in vivo and ex vivo gamma probing was performed during the surgery, which included backup extended lymph node dissection. Radioactivity of the excised lymph nodes was measured and validated with an autowell scintillation counter. RESULTS: Radioactive positive (hot) nodes were identified in 17 of the 24 (70.8%) patients by lymphoscintigraphy, in 21 of 24 (87.5%) patients by in vivo probing and in 23 of 24 (95.8%) patients by ex vivo probing. On an individual basis the numbers of hot nodes identified by lymphoscintigraphy and in vivo probing were low (40% and 36%, respectively) compared to the high detection rate for ex vivo probing (91%). CONCLUSIONS: Although sentinel lymph nodes can be used for prostate cancer, detailed lymph node mapping and extended dissection backup are currently needed. It is also important to establish novel procedures for accurate and complete removal of all hot nodes.

Aged↗
PubMed2004

Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinoma.

BACKGROUND: Although a correlation between microvessel density (MVD) and tumor aggressiveness has been established for several malignancies, the data for renal cell carcinoma (RCC) is conflicting. In order to clarify the significance of MVD, we investigated the relationships between MVD and tumor stage, grade, size, occurrence of metastasis and patient survival. METHODS: Tumor specimens from 70 patients with primary renal cell carcinoma were examined by immunohistochemical staining for CD34. RESULTS: There was a tendency for MVD to decrease from G1 to G3 tumors or from stage T1 to T3 tumors, although this was not statistically significant. However, the MVD for 56 non-metastatic and 14 metastatic tumors were significantly different (P = 0.005) at 109 +/- 67 and 58 +/- 35 per x400 field (mean +/- SD), respectively. Microvessel density for 36 large and 34 small tumors was also significantly different (P < 0.0001) at 48 +/- 22 and 142 +/- 54 per x400 field, respectively. The survival rate of patients with small, low grade and hypervascular tumors was significantly higher than that of patients with large (P = 0.0015), high grade (P = 0.05) or low MVD (P = 0.039) tumors. Cox proportional hazards regression analysis showed that tumor grade and size emerged as independent prognostic factors. CONCLUSION: High MVD in RCC was inversely associated with tumor aggressiveness, but MVD was not the independent prognostic factor.

Antigens, CD34↗
PubMed2004

Electrochemical and luminescent properties of new mononuclear ruthenium(II) and binuclear iridium(III)-ruthenium(II) terpyridine complexes.

Hexafluorophosphate salts of mononuclear complexes [Ru(II)Cl(L)(terpy)]+ (L = dmbpy (1); dpbpy (2), sambpy (3), and dpp (7), and binuclear complexes [Ru(II)2Cl2(dpp)(terpy)2]2+ (8) and [Ir(III)Ru(II)Cl2(dpp)(terpy)2]3+ (9) were prepared and characterized. Abbreviations of the ligands are bpy = 2,2'-bipyridine, dmbpy = 4,4'-dimethyl-2,2'-bipyridine, dpbpy = 4,4'-diphenyl-2,2'-bipyridine, dpp = 2,3-bis(2-pyridyl)pyrazine, sambpy = 4,4'-bis((S)-(+)-alpha-1-phenylethylamido)-2,2'-bipyridine, and terpy = 2,2':6',2''-terpyridine. The absorption spectra of 8 and 9 are dominated by ligand-centered bands in the UV region and by metal-to-ligand charge-transfer bands in the visible region. The details of their spectroscopic and electrochemical properties were investigated. In both binuclear complexes, it has been found that the HOMO is based on the Ru metal, and LUMO is dpp-based. [Ir(III)Ru(II)Cl2(dpp)(terpy)2]3+, indicating intense emission at room temperature, and a lifetime of 154 ns. The long lifetime of this bimetallic chromophore makes it a useful component in the design of supramolecular complexes.

Journal Article↗
PubMed2004

Electrochemical and phosphorescent properties of new Ir(III) complexes coordinated by various bipyridine derivatives.

Four useful polypyridine iridium(III) complexes in the form of [IrCl2L2]+ were prepared and their spectroscopic and electrochemical properties as well as X-ray crystallography were investigated. The ligands used were L = 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine, 4,4'-diphenyl-2,2'-bipyridine, 1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline, and 2,2'-biquinoline. Synthetic methods were developed by a sequential ligand-replacement, which occurred in the reaction vessel using a microwave oven. All complexes showed that LUMOs are based on the pi-system contribution of the polypyridine ligand for [IrCl2(bpy)2]+, [IrCl2(dmbpy)2]+, [IrCl2(dpbpy)2]+, [IrCl2(phen)2]+, [IrCl2(dpphen)2]+ and [IrCl2(bqn)2]+. The HOMOs are also localized on the polypyridine ligand in the iridium complexes. It was found that [IrCl2L2]+ emits intense phosphorescence at room temperature. In particular, the use of dpbpy as ancillary ligands extends the lifetime (660 ns) of the 3(pi-pi*) excited states of Ir(III) polypyridine complexes. The complex [IrCl2(bqn)2]+ with electron acceptor substituents shows a large red-shift to 622 nm. It is noticed that iridium polypyridine complexes show intense emissions at various colors, such as yellow for [IrCl2(dmbpy)2]+ and red for [IrCl2(bqn)2]+ which can be applied to photosensitizers. The spectroscopic and electrochemical details are also reported herein.

Journal Article↗
PubMed2004

[Update on hereditary neuropathy].

Hereditary neuropathies are classified into several subtypes according to clinical, electrophysiologic and pathologic findings. Recent genetic studies have revealed their phenotypic and genetic diversities. In the primary peripheral demyelinating neuropathies (CMT1), at least 15 genes have been associated with the disorders; altered dosage or point mutation of PMP22, GJB1, MPZ, EGR2, MTMR2, NDRG1, PRX, SOX10, GDAP1 and MTMR13/SBF2. In the primary peripheral axonal neuropathies (CMT2), at least 10 genes have been associated with these disorders; NEFL, KIF1B, MFN2, GAN1, LMNA, RAB7, GARS, TDP1, APTX, and SETX. In addition, some mutations in GJB1, MPZ, GDAP1 and NEFL also present with clinical and electrophysiologic findings of CMT2. Patients with TDP1, APTX or SETX mutations share common clinical findings; autosomal recessive inheritance, cerebellar ataxia, and axonal neuropathy. These genes are suspected to be related to DNA/RNA repair and induce cell death especially in neuronal cells. In addition to the above diseases, we have reported a new type of NMSNP (MIM# * 604484) characterized by proximal dominant neurogenic atrophy, obvious sensory nerve involvement and the gene locus on 3q12.3. Here, we summarize the genetic bases of hereditary neuropathies and attempt to highlight significant genotype-phenotype correlations with a special interest in nonsense-mediated mRNA decay pathway.

Demyelinating Diseases↗
PubMed2003

A case of adult-onset Alexander disease with Arg416Trp human glial fibrillary acidic protein gene mutation.

Heterozygous point mutations in the coding region of the human glial fibrillary acidic protein (GFAP) gene have been reported in patients with various forms of Alexander disease (AD). We report a case of genetically confirmed adult-onset AD with palatal myoclonus, pyramidal tract signs, cerebellar signs, and marked atrophy of the medulla oblongata and spinal cord, autonomic dysfunction and heterozygous R416W GFAP mutation. Interestingly, this R416W mutation has also been reported in both infantile and juvenile forms of Alexander disease. The fact that a R416W mutation causes various types of AD suggests that clinical severities of AD are due not only to the different sites and nature of mutations in GFAP, but also to other modifying factor(s).

Adult↗
PubMed2003

Detection of the 14-3-3 protein in the cerebrospinal fluid of Japanese multiple sclerosis patients presenting with severe myelitis.

Recent studies showed that the 14-3-3 protein is detectable in the cerebrospinal fluid (CSF) of prion-unrelated neurological diseases, such as meningoencephalitis and myelitis. To investigate the possible association between the amounts of the 14-3-3 protein in the CSF and the clinical severity of multiple sclerosis (MS), its levels were determined by Western blot in the CSF of the patients with relapsing-remitting MS (RRMS) (n=10), secondary progressive MS (SPMS) (n=7), primary progressive MS (PPMS) (n=2), and non-MS inflammatory diseases of the CNS (n=5). The 14-3-3 protein was identified in seven CSF samples, including four patients with SPMS in acute relapse, one with SPMS in remission accompanied by fresh cerebral infarction, one with RRMS in acute relapse, and one with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy. The patients positive for the CSF 14-3-3 protein immunoreactivity showed more severe disability and higher levels of pleocytosis, protein, IgG, beta2-microglobulin, and neuron-specific enolase in the CSF, compared with those negative for its immunoreactivity. Four of these patients exhibited extensive lesions distributed along multiple vertebral segments in the spinal cord on MRI. In contrast, none of the MS patients without an extensive involvement of the spinal cord showed the CSF 14-3-3 protein immunoreactivity. These results suggest that detection of the 14-3-3 protein in the CSF provides a marker for severe inflammation-induced extensive damage of the central nervous system tissues responsible for poor therapeutic responses and irreversible neurological deficits in MS.

14-3-3 Proteins↗
PubMed2003

Interferon therapy-responsive brain metabolic abnormalities in a case of adult-onset subacute sclerosing panencephalitis evaluated by 1H MRS analysis.

We describe a 22-year-old woman with an adult-onset, slowly progressive form of subacute sclerosing panencephalitis (SSPE), who was repeatedly evaluated by brain magnetic resonance spectroscopy (MRS). The brain lesion spectrum showed a decrease in N-acetylaspartate (NAA) resonance, an increase in inositol (Ins) resonance, and an unaltered choline signal. These findings suggest neuronal loss and reactive gliosis without inflammation, consistent with brain biopsy findings showing astrocytic proliferation unaccompanied by lymphocytic infiltrates. The unusually protracted clinical course might be attributable to an absence of inflammatory infiltrates in the brain. Intraventricular interferon injection plus oral inosine pranobex treatment produced a substantial improvement in the MRS findings, suggesting the validity of monitoring MRS in SSPE.

Adult↗
PubMed2003

Remarkably stereoselective photoinduced electron-transfer reaction between zinc myoglobin and optically active binaphthyl bisviologen.

We have designed and synthesized new optically active bisviologens ([BNMV](4+)) containing a binaphthyl moiety to examine the stereoselective photoinduced electron-transfer (ET) reactions with zinc-substituted myoglobin (ZnMb) by flash photolysis. The photoexcited triplet state of ZnMb, (3)(ZnMb)*, was successfully quenched by [BNMV](4+) ions to form the radical pair of a ZnMb cation (ZnMb(.+)) and a reduced viologen ([BNMV](.3+)), followed by a thermal ET reaction to the ground state. The rate constants ( k(q)) for the ET quenching at 25 degrees C were obtained as k(q)( R)=(2.9+/-0.2)x10(7) M(-1) s(-1) and k(q)( S)=(2.2+/-0.2)x10(7) M(-1) s(-1), respectively. The ratio of k(q)( R)/ k(q)( S)=1.3 indicates that the ( R)-isomer of the chiral viologen preferentially quenches (3)(ZnMb)*. On the other hand, the rate constants ( k) for the thermal ET reaction from [BNMV](.3+) to ZnMb(-+) at 25 degrees C were k( R)=(1.2+/-0.1)x10(8) M(-1) s(-1) and k( S)=(0.47+/-0.03)x10(8) M(-1) s(-1), respectively, and the ratio remarkably increased to k( R)/ k( S)=2.6. The activation parameters, Delta H(not equal) and Delta S(not equal), were determined from the kinetic measurements at various temperatures (10-30 degrees C) to understand the ET mechanisms. In the quenching reaction, the energy differences of Delta Delta H*(R- S) and T Delta Delta S*( R- S) at 25 degrees C were calculated to be -3.9+/-1.6 and -3.3+/-0.2 kJ mol(-1), respectively, whereas Delta Delta H*( R-S)=7.7+/-1.9 kJ mol(-1 )and T Delta Delta S*( R-S)=9.9+/-0.5 kJ mol(-1 )were found for the thermal ET reaction. Therefore, the thermal ET reaction to the ground state was proved to be dominated by the entropy term, and the large stereoselectivity may arise from the decrease in charge repulsion between donor and acceptor.

Animals↗
PubMed2003

CMT4A: identification of a Hispanic GDAP1 founder mutation.

Mutations of the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) cause autosomal recessive Charcot-Marie-Tooth disease type 4A. We report four additional families with recessive mutations (487C-->T, Q163X; 359G-->A, R120Q) of GDAP1; Q163X occurred in three unrelated Hispanic families that had the same haplotype suggesting a Spanish founder mutation. Both the Q163X and the R120Q mutation cause demyelination and axonal loss. The patients had symptoms within the first two years of life and involvement of cranial, sensory, and enteric nerves. Neuropathology showed loss of large myelinated fibers, onion bulb formations and focal folding of the outer myelin lamina.

Adolescent↗