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Biomedical subjects

T Kurihara

Publications and source records attributed to T Kurihara.

At least 109 records · Page 6Linked to original sources

[Myotonia and channelopathy].

Myotonia occurs with abnormalities of the muscle membrane, and there have been reports of various channel abnormalities including Cl, Na, and Ca channels. Historically in 1966, Lipicky and Bryant found the abnormality of the muscle Cl channel in Thomsen's disease and hereditary myotonia of goat. Thereafter, Na channel abnormality was found in myotonia associated with familial hyperkalemic periodic paralysis and paramyotonia congenita by using patch clamp technique. Myotonic dystrophy is the most common myotonic disorder and genetic studies disclosed the presence of abnormal triplet repeat in the chromosome 19q13.1 and the gene product is known as myotonin protein kinase. However, pathophysiological mechanism of myotonia in myotonic dystrophy is not yet clear except that there are mild decrease of Cl conductance in 5 out of 8 muscle fibers and late opening of Na channels also occurs. As for the treatment of myotonia, medications which work as Na channel blockers have been used and they are effective to reduce myotonia, but they do not improve muscle weakness. Recently dehydroepiandrosterone sulfate which is a male hormone secreted from the adrenal cortex has been used for myotonic dystrophy and the drug reduces myotonia and improves activities of daily living. The author confirmed that myotonia can be induced in the muscle preparations of mice by either anthracene-9-carboxylic acid (Cl channel blocker), or by anemone toxin (blocker of inactivation of Na channel), and dehydroepiandrosterone sulfate can reduce myotonic bursts in both of these muscle preparations by intracellular recordings.

Animals↗

Reaction mechanism of fluoroacetate dehalogenase from Moraxella sp. B.

Fluoroacetate dehalogenase (EC 3.8.1.3) catalyzes the dehalogenation of fluoroacetate and other haloacetates. The amino acid sequence of fluoroacetate dehalogenase from Moraxella sp. B is similar to that of haloalkane dehalogenase (EC 3.8.1.5) from Xanthobacter autotrophicus GJ10 in the regions around Asp-105 and His-272, which correspond to the active site nucleophile Asp-124 and the base catalyst His-289 of the haloalkane dehalogenase, respectively (Krooshof, G. H., Kwant, E. M., Damborský, J., Koca, J., and Janssen, D. B. (1997) Biochemistry 36, 9571-9580). After multiple turnovers of the fluoroacetate dehalogenase reaction in H218O, the enzyme was digested with trypsin, and the molecular masses of the peptide fragments formed were measured by ion-spray mass spectrometry. Two 18O atoms were shown to be incorporated into the octapeptide, Phe-99-Arg-106. Tandem mass spectrometric analysis of this peptide revealed that Asp-105 was labeled with two 18O atoms. These results indicate that Asp-105 acts as a nucleophile to attack the alpha-carbon of the substrate, leading to the formation of an ester intermediate, which is subsequently hydrolyzed by the nucleophilic attack of a water molecule on the carbonyl carbon atom. A His-272 --> Asn mutant (H272N) showed no activity with either fluoroacetate or chloroacetate. However, ion-spray mass spectrometry revealed that the H272N mutant enzyme was covalently alkylated with the substrate. The reaction of the H272N mutant enzyme with [14C]chloroacetate also showed the incorporation of radioactivity into the enzyme. These results suggest that His-272 probably acts as a base catalyst for the hydrolysis of the covalent ester intermediate.

Acetates↗

Crystal structures of reaction intermediates of L-2-haloacid dehalogenase and implications for the reaction mechanism.

Crystal structures of L-2-haloacid dehalogenase from Pseudomonas sp. YL complexed with monochloroacetate, L-2-chlorobutyrate, L-2-chloro-3-methylbutyrate, or L-2-chloro-4-methylvalerate were determined at 1.83-, 2.0-, 2.2-, and 2.2-A resolutions, respectively, using the complex crystals prepared with the S175A mutant, which are isomorphous with those of the wild-type enzyme. These structures exhibit unique structural features that correspond to those of the reaction intermediates. In each case, the nucleophile Asp-10 is esterified with the dechlorinated moiety of the substrate. The substrate moieties in all but the monochloroacetate intermediate have a D-configuration at the C2 atom. The overall polypeptide fold of each of the intermediates is similar to that of the wild-type enzyme. However, it is clear that the Asp-10-Ser-20 region moves to the active site in all of the intermediates, and the Tyr-91-Asp-102 and Leu-117-Arg-135 regions make conformational changes in all but the monochloroacetate intermediates. Ser-118 is located near the carboxyl group of the substrate moiety; this residue probably serves as a binding residue for the substrate carboxyl group. The hydrophobic pocket, which is primarily composed of the Tyr-12, Gln-42, Leu-45, Phe-60, Lys-151, Asn-177, and Trp-179 side chains, exists around the alkyl group of the substrate moiety. This pocket may play an important role in stabilizing the alkyl group of the substrate moiety through hydrophobic interactions, and may also play a role in determining the stereospecificity of the enzyme. Moreover, a water molecule, which is absent in the substrate-free enzyme, is present in the vicinities of the carboxyl carbon of Asp-10 and the side chains of Asp-180, Asn-177, and Ala-175 in each intermediate. This water molecule may hydrolyze the ester intermediate and its substrate. These findings crystallographically demonstrate that the enzyme reaction proceeds through the formation of an ester intermediate with the enzyme's nucleophile Asp-10.

Binding Sites↗

Impaired macrophage function and enhanced T cell-dependent immune response in mice lacking CCR5, the mouse homologue of the major HIV-1 coreceptor.

The CC-chemokine receptor CCR5 has been shown to be the major coreceptor for HIV-1 entry into cells, and humans with homozygous mutation in the ccr5 gene are highly resistant to HIV-1 infection, despite the existence of many other HIV-1 coreceptors. To investigate the physiologic function of CCR5 and to understand the cellular mechanisms of these clinical observations, we generated a CCR5-deficient mouse model (ccr5[-/-]) by targeted deletion of the ccr5 gene. We found that although developed normally in a pathogen-free environment, CCR5-deficient mice showed reduced efficiency in clearance of Listeria infection and exert a protective effect against LPS-induced endotoxemia, reflecting a partial defect in macrophage function. In addition, CCR5-deficient mice had an enhanced delayed-type hypersensitivity reaction and increased humoral responses to T cell-dependent antigenic challenge, indicating a novel role of CCR5 in down-modulating T cell-dependent immune response.

Animals↗

Cardiac-specific overexpression of angiotensin II AT2 receptor causes attenuated response to AT1 receptor-mediated pressor and chronotropic effects.

Angiotensin (Ang) II has two major receptor isoforms, AT1 and AT2. Currently, AT1 antagonists are undergoing clinical trials in patients with cardiovascular diseases. Treatment with AT1 antagonists causes elevation of plasma Ang II which selectively binds to AT2 and exerts as yet undefined effects. Cardiac AT2 level is low in adult hearts, whereas its distribution ratio is increased during cardiac remodeling and its action is enhanced by application of AT1 antagonists. Although in AT2 knock-out mice sensitivity to the pressor action of Ang II was increased, underlying mechanisms remain undefined. Here, we report the unexpected finding that cardiac-specific overexpression of the AT2 gene using alpha-myosin heavy chain promoter resulted in decreased sensitivity to AT1-mediated pressor and chronotropic actions. AT2 protein undetectable in the hearts of wild-type mice was overexpressed in atria and ventricles of the AT2 transgenic (TG) mice and the proportions of AT2 relative to AT1 were 41% in atria and 45% in ventricles. No obvious morphological change was observed in the myocardium and there was no significant difference in cardiac development or heart to body weight ratio between wild-type and TG mice. Infusion of Ang II to AT2 TG mice caused a significantly attenuated increase in blood pressure response and the change was completely blocked by pretreatment with AT2 antagonist. This decreased sensitivity to Ang II-induced pressor action was mainly due to the AT2-mediated strong negative chronotropic effect and exerted by circulating Ang II in a physiological range that did not stimulate catecholamine release. Isolated hearts of AT2 transgenic mice perfused using a Langendorff apparatus also showed decreased chronotropic responses to Ang II with no effects on left ventricular dp/dt max values, and Ang II-induced activity of mitogen-activated protein kinase was inhibited in left ventricles in the transgenic mice. Although transient outward K+ current recorded in cardiomyocytes from AT2 TG mice was not influenced by AT2 activation, this study suggested that overexpression of AT2 decreases the sensitivity of pacemaker cells to Ang II. Our results demonstrate that stimulation of cardia AT2 exerts a novel antipressor action by inhibiting AT1-mediated chronotropic effects, and that application of AT1 antagonists to patients with cardiovascular diseases has beneficial pharmacotherapeutic effects of stimulating cardiac AT2.

Angiotensin II↗

Determination of a normal level of serum CA125 in postmenopausal women as a tool for preoperative evaluation and postoperative surveillance of endometrial carcinoma.

In an attempt to determine a normal level of CA125 in postmenopausal women, CA125 levels of normal postmenopausal women (n = 36, 58.2 +/- 8.1 years) and postmenopausal women undergoing hormone replacement therapy (HRT) (n = 111, 56.8 +/- 6.1 years) were studied. A mean CA125 concentration of 10.0 +/- 3.8 U/ml was found in postmenopausal women without HRT and was significantly lower than that of postmenopausal women undergoing HRT (12.8 +/- 3.8 U/ml), indicating that the cutoff level of CA125 in postmenopausal women or women without reproductive organs should be estimated at a level lower than that conventionally accepted. A receiver operating characteristic (ROC) curve for a preoperative evaluation of myometrial invasion was analyzed in postmenopausal women with endometrial cancer (n = 110). A novel cutoff level of 20 U/ml of CA125 could detect myometrial invasion to more than one-half of the myometrium with sensitivity of 69.0%, specificity of 74.1%, positive predictive value of 58.8%, and negative predictive value of 81.6%. In addition, the distribution of CA125 levels was analyzed in patients who had undergone an operation for endometrial cancer more than 2 years earlier and as yet had no clinical evidence of recurrence of the disease. Ninety-six point two percent of 619 measurement values were lower than 20 U/ml. These results suggest that the novel CA125 level of 20 U/ml is clinically useful for preoperative evaluation and postoperative surveillance of endometrial carcinoma.

Aged↗

Multidrug-resistant recurrent breast cancer which responded to medroxyprogesterone acetate showing a remarkable improvement in the quality of life: report of a case and the role of team medical care.

We herein report the case of a patient with recurrent breast cancer who showed a remarkable improvement in her quality of life (QOL) as a result of a good response to medroxyprogesterone acetate (MPA). A 43-year-old Japanese woman developed bone metastases 3 years after surgery. Subsequent radiotherapy and chemoendocrine therapy with CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and tamoxifen all failed, and she could not sit up because of bone metastases. The performance status (PS) on admission was grade 4. After admission, delirium accompanied with sensory and visual hallucination caused by intense anxiety occurred, and a continuous consultation by psychiatrists was necessary. MPA treatment at the dose of 1200 mg/day alleviated the bone pain, thus improving her PS to grade 1. Her appetite also improved, while her mental state stabilized. A bone scintigram revealed an improvement of bone metastases, and the tumor markers also returned to normal values. The patient thus showed a pronounced improvement in her QOL due to both MPA treatment and team medical care. The role of the medical staff as well as the importance of their cooperation in achieving an improvement in the QOL of cancer patients is also discussed.

Adult↗

Construction and expression of a mouse-human chimeric antibody against human tumor necrosis factor-alpha.

A mouse anti-human tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody (MoAb), designated as 3B10, has previously been produced and characterized by our laboratory. We report here the construction and the expression of mouse-human chimeric antibody derived from the MoAb. cDNAs encoding variable regions of heavy and light chains were prepared from 3B10 cells by polymerase chain reaction, and introduced to mammalian expression vectors containing cDNA for human gamma1 and kappa constant regions, respectively. Cotransfection of the vectors into CHO cells resulted in production of antibody reacting with human TNF-alpha. In SDS-PAGE analysis, the chimeric antibody, c3B10, migrated at 170 kDa under a nonreducing condition, whereas two bands with 58 and 28 kDa appeared following treatment with 2-mercaptoethanol. Both c3B10 and mouse 3B10 neutralized the cytotoxic activity of human TNF-alpha to the same level, indicating that c3B10 holds the binding activity of its original MoAb. These findings suggest that the introduced genes for chimeric heavy and light chains are transcribed and translated to produce the chimeric heavy and light chain peptides, and that the peptides are assembled to form native IgG molecule. The chimeric anti-TNF-alpha antibody described in this study is expected to be less immunogenic and thus more suitable for possible clinical use.

Animals↗

X-ray structure of a reaction intermediate of L-2-haloacid dehalogenase with L-2-chloropropionamide.

The crystal structure of a complex prepared by soaking a single crystal of the S175A mutant of L-2-haloacid dehalogenase from Pseudomonas sp. YL in a solution containing a poor substrate, L-2-chloropropionamide, has been determined by X-ray analysis at 2. 15 A resolution with a crystallographic R factor of 19.8%. The present analysis has revealed the structure of the reaction intermediate trapped in the crystal. In the intermediate, the substrate moiety lacking chlorine is covalently bound to the carboxyl group of D10, and adopts the pro-D-configuration at the C2 atom. The amide group of the substrate is hydrogen-bonded with the hydroxy group of S118. The methyl group bound to the C2 atom exists in a hydrophobic pocket which is important for recognition of the alkyl group of the substrate. The guanidino group of R41 has reasonable orientation for halogen-abstraction.

Amides↗

A transcultural study of psychopharmacotherapy for schizophrenia of neuroleptic treatment between Tokyo and Bali.

We made a comparison of drug treatment for the patients with schizophrenia between two psychiatric hospitals in Tokyo, Japan, and Bali, Indonesia. An initial preliminary, cross-sectional study revealed that the mean daily dose of neuroleptics was significantly higher in Tokyo than it was in Bali. A second, longitudinal, study showed that the mean neuroleptic dose for newly admitted patients in the acute phase was higher, and the number of patients receiving maintenance treatment after discharge larger in Tokyo, while the mean duration of hospitalization was shorter, and the re-admission rate 1 year after discharge lower in Bali. These findings suggest that the course of schizophrenia is more favorable in Bali. As a result of lower dose of neuroleptics, the prevalence of tardic dyskinesia was much lower in Bali than it was in Tokyo.

Adult↗

A cold-adapted lipase of an Alaskan psychrotroph, Pseudomonas sp. strain B11-1: gene cloning and enzyme purification and characterization.

A psychrotrophic bacterium producing a cold-adapted lipase upon growth at low temperatures was isolated from Alaskan soil and identified as a Pseudomonas strain. The lipase gene (lipP) was cloned from the strain and sequenced. The amino acid sequence deduced from the nucleotide sequence of the gene (924 bp) corresponded to a protein of 308 amino acid residues with a molecular weight of 33,714. LipP also has consensus motifs conserved in other cold-adapted lipases, i.e., Lipase 2 from Antarctic Moraxella TA144 (G. Feller, M. Thirty, J. L. Arpigny, and C. Gerday, DNA Cell Biol. 10:381-388, 1991) and the mammalian hormone-sensitive lipase (D. Langin, H. Laurell, L. S. Holst, P. Belfrage, and C. Holm, Proc. Natl. Acad. Sci. USA 90:4897-4901, 1993): a pentapeptide, GDSAG, containing the putative active-site serine and an HG dipeptide. LipP was purified from an extract of recombinant Escherichia coli C600 cells harboring a plasmid coding for the lipP gene. The enzyme showed a 1,3-positional specificity toward triolein. p-Nitrophenyl esters of fatty acids with short to medium chains (C4 and C6) served as good substrates. The enzyme was stable between pH 6 and 9, and the optimal pH for the enzymatic hydrolysis of tributyrin was around 8. The activation energies for the hydrolysis of p-nitrophenyl butyrate and p-nitrophenyl laurate were determined to be 11.2 and 7.7 kcal/mol, respectively, in the temperature range 5 to 35 degrees C. The enzyme was unstable at temperatures higher than 45 degrees C. The Km of the enzyme for p-nitrophenyl butyrate increased with increases in the assay temperature. The enzyme was strongly inhibited by Zn2+, Cu2+, Fe3+, and Hg2+ but was not affected by phenylmethylsulfonyl fluoride and bisnitrophenyl phosphate. Various water-miscible organic solvents, such as methanol and dimethyl sulfoxide, at concentrations of 0 to 30% (vol/vol) activated the enzyme.

Cloning, Molecular↗

Purification, characterization, and mechanism of a flavin mononucleotide-dependent 2-nitropropane dioxygenase from Neurospora crassa.

A nitroalkane-oxidizing enzyme was purified to homogeneity from Neurospora crassa. The enzyme is composed of two subunits; the molecular weight of each subunit is approximately 40,000. The enzyme catalyzes the oxidation of nitroalkanes to produce the corresponding carbonyl compounds. It acts on 2-nitropropane better than on nitroethane and 1-nitropropane, and anionic forms of nitroalkanes are much better substrates than are neutral forms. The enzyme does not act on aromatic compounds. When the enzyme reaction was conducted in an 18O2 atmosphere with the anionic form of 2-nitropropane as the substrate, acetone (with a molecular mass of 60 Da) was produced. This indicates that the oxygen atom of acetone was derived from molecular oxygen, not from water; hence, the enzyme is an oxygenase. The reaction stoichiometry was 2CH3CH(NO2)CH3 + O2-->2CH3COCH3 + 2HNO2, which is identical to that of the reaction of 2-nitropropane dioxygenase from Hansenula mrakii. The reaction of the Neurospora enzyme was inhibited by superoxide anion scavengers in the same manner as that of the Hansenula enzyme. Both of these enzymes are flavoenzymes; however, the Neurospora enzyme contains flavin mononucleotide as a prosthetic group, whereas the Hansenula enzyme contains flavin adenine dinucleotide.

Acetone↗

[Prognostic value of myocardial 123I-BMIPP imaging in patients with congestive heart failure without coronary artery disease].

We performed 123I-BMIPP (BMIPP) imaging in order to clarify the characteristics of fatty acid metabolism and its effect on prognosis in patients with congestive heart failure (CHF) without coronary artery disease. We studied 15 normal subjects and 42 patients with CHF (idiopathic dilated cardiomyopathy; 24, hypertensive heart disease; 12, valvular heart disease; 6). We obtained cardiac imaging with BMIPP and 201Tl at rest on separate days before discharge. Using whole body imaging, the ratio of cardiac uptake of the isotope to total injected dose was calculated (%Uptake). We calculated the cardiac uptake ratio of BMIPP (%Uptake of BMIPP divided by %Uptake of 201Tl), percent washout of BMIPP from the heart over 3 hours and unhomogeneity of myocardial distribution of BMIPP (coefficient of variation of BMIPP, CV) as scintigraphic parameters. Cardiac events were defined as cardiac death or deterioration of CHF which requiring readmission. Uptake ratio (CHF: 0.91 +/- 0.17, normal; 1.10 +/- 0.09, p = 0.0000) and CV (CHF; 20 +/- 5, normal; 16 +/- 5, p = 0.0385) were different significantly between CHF and normal subjects. During the follow-up period of 27.2 +/- 14.4 months (4.5-53.5 months) cardiac events developed in 15 patients (cardiac death; 8, deterioration of CHF; 7). In univariate analysis, %uptake of 201Tl, uptake ratio, % FS, serum norepinephrine level and serum renin activity were different significantly between event and event-free groups. Cox proportional hazard analysis showed that the uptake ratio (p = 0.0000) and age (p = 0.018) were independent predictors of cardiac events. In patients with uptake ratio less than 0.88, relative risks of cardiac events was 23.7 times greater than in patients with uptake ratio more than 0.89. These data suggested that in patients with CHF fatty acid metabolism was deteriorated and cardiac uptake of BMIPP was a strong and independent predictor of long-term prognosis in patients with heart failure.

Adult↗

[Evaluation of long-term prognosis in patients with heart failure: is cardiac imaging with iodine-123 metaiodobenzylguanidine useful?].

The effect of cardiac sympathetic activity on long-term prognosis in patients with heart failure was evaluated by cardiac imaging with iodine-123 metaiodobenzylguanidine (123I-MIBG) in 46 patients admitted for the first episode of heart failure (idiopathic dilated cardiomyopathy: 18, ischemic heart disease: 10, hypertensive heart disease: 7, valvular heart disease: 4, others: 7). Cardiac imaging was performed with 123I-MIBG and thallium-201 (201Tl) at rest on separate days before discharge. Using whole body imaging, the ratio of cardiac uptake of the isotope to total injected dose was calculated (percentage uptake). The cardiac uptake ratio of 123I-MIBG (percentage uptake of 123I-MIBG divided by percentage uptake of 201Tl) and percentage washout of 123I-MIBG from the heart over 3 hours were calculated as scintigraphic parameters. Cardiac events were defined as cardiac death or deterioration of heart failure requiring readmission. Scintigraphic parameters, clinical parameters, left ventricular function obtained by echocardiography and neurohumoral parameters were compared between the event group and event-free group. During the follow-up period of 26.9 +/- 13.9 (7.1-53.8 months), cardiac events developed in 14 patients (cardiac death in 10 and deterioration of heart failure in 4; 30%). Univariate analysis showed uptake ratio and washout rate of 123I-MIBG, percentage uptake of 201Tl, New York Heart Association class at discharge, fractional shortening of the left ventricle, serum norepinephrine and atrial natriuretic peptide levels differed significantly between the two groups. Cox proportional-hazard analysis showed that the uptake ratio was an independent predictor of cardiac events (p < 0.0001). When a cut-off point in the uptake ratio equal to or less than 0.50 and age equal to or more than 65 years old were included in the Cox proportional-hazard analysis instead of actual numbers, relative risks of cardiac events by each index were 31.2 (95% confidence interval, 3.9 to 247.6; p = 0.001) and 4.2 (p = 0.025), respectively. These data suggest that cardiac uptake of 123I-MIBG is a strong and independent predictor of long-term prognosis in patients with heart failure.

3-Iodobenzylguanidine↗

Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor.

Chemokines are a structurally related family of cytokines that are important for leukocyte trafficking. The C-C chemokine monocyte chemoattractant protein-1 (MCP-1) is a potent monocyte activator in vitro and has been associated with monocytic infiltration in several inflammatory diseases. One C-C chemokine receptor, CCR2, has been identified that mediates in vitro responses to MCP-1 and its close structural homologues. CCR2 has also recently been demonstrated to be a fusion cofactor for several HIV isolates. To investigate the normal physiological function of CCR2, we generated mice with a targeted disruption of the ccr2 gene. Mice deficient for CCR2 developed normally and had no hematopoietic abnormalities. However, ccr2(-/-) mice failed to recruit macrophages in an experimental peritoneal inflammation model. In addition, these mice were unable to clear infection by the intracellular bacteria, Listeria monocytogenes. These results suggest that CCR2 has a nonredundant role as a major mediator of macrophage recruitment and host defense against bacterial pathogens and that MCP-1 and other CCR2 ligands are effectors of those functions.

Animals↗

Cysteine sulfinate desulfinase, a NIFS-like protein of Escherichia coli with selenocysteine lyase and cysteine desulfurase activities. Gene cloning, purification, and characterization of a novel pyridoxal enzyme.

Selenocysteine lyase (EC 4.4.1.16) exclusively decomposes selenocysteine to alanine and elemental selenium, whereas cysteine desulfurase (NIFS protein) of Azotobacter vinelandii acts indiscriminately on both cysteine and selenocysteine to produce elemental sulfur and selenium respectively, and alanine. These proteins exhibit some sequence homology. The Escherichia coli genome contains three genes with sequence homology to nifS. We have cloned the gene mapped at 63.4 min in the chromosome and have expressed, purified to homogeneity, and characterized the gene product. The enzyme comprises two identical subunits with 401 amino acid residues (Mr 43,238) and contains pyridoxal 5'-phosphate as a coenzyme. The enzyme catalyzes the removal of elemental sulfur and selenium atoms from L-cysteine, L-cystine, L-selenocysteine, and L-selenocystine to produce L-alanine. Because L-cysteine sulfinic acid was desulfinated to form L-alanine as the preferred substrate, we have named this new enzyme cysteine sulfinate desulfinase. Mutant enzymes having alanine substituted for each of the four cysteinyl residues (Cys-100, Cys-176, Cys-323, and Cys-358) were all active. Cys-358 corresponds to Cys-325 of A. vinelandii NIFS, which is conserved among all NIFS-like proteins and catalytically essential (Zheng, L., White, R. H., Cash, V. L., and Dean, D. R. (1994) Biochemistry 33, 4714-4720), is not required for cysteine sulfinate desulfinase. Thus, the enzyme is distinct from A. vinelandii NIFS in this respect.

Amino Acid Sequence↗

Molecular evolution of myelin proteolipid protein.

We show that the major membrane protein of central nervous system myelin, proteolipid protein, evolved much more rapidly than it does now more than 300 million years ago. We reason that myelin proteolipid protein evolved rapidly just after its appearance in vertebrates and that its evolutionary rate then gradually decreased. Comparison of the rates between the synonymous and nonsynonymous nucleotide substitutions for the cDNA suggests the possibility that positive selection operated on myelin proteolipid protein at least when it appeared in vertebrates.

Amino Acid Sequence↗