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M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 721 records · Page 40Linked to original sources
PubMed1992

[A case of the right aortic arch with the left subclavian artery as its last branch].

A case of the right aortic arch with the left subclavian artery as its last branch was found in an 80-year-old Japanese female cadaver during the 1990 dissection for students. The main findings were as follows. The ascending aorta arose from the left ventricle and ran right and upward to the level of the intervertebral disc between the 2nd and 3rd thoracic vertebrae. It then curved right and backward to form the aortic arch. The aortic arch joined the thoracic aorta that descended along the right side of the vertebral column and crossed obliquely the vertebral column at the level of the 8th thoracic vertebra. Finally it entered the abdomen through the aortic hiatus behind the esophagus. Four branches were given off from the aortic arch in the following order from left to right: the left common carotid, the right common carotid, and the right subclavian and the left subclavian arteries. The left subclavian artery, which had an aortic diverticulum at the origin of the aortic arch, ran left and upward behind the esophagus. The ligamentum arteriosum connected the left pulmonary artery with the aortic diverticulum of the left subclavian artery. The left common carotid artery, which normally had no branches before entering the cranium, gave off an accessory esophageal branch about 20 mm distally from its origin. The right and left vertebral arteries entered the transverse foramen of the 6th cervical vertebra. The left recurrent laryngeal nerve hooked around from the left dorsal to the right ventral part of the ligamentum arteriosum.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Cytogenetic 2; 18 and 18; 22 translocation in chronic lymphocytic leukemia with juxtaposition of bcl-2 and immunoglobulin light chain genes.

The majority of follicular lymphoma cells carry the typical chromosome translocation 14;18, which juxtaposes the bcl-2 gene to the immunoglobulin heavy-chain (IgH) gene. Variant translocations of the bcl-2 gene to the Ig lambda or Ig kappa gene have been found by molecular biological techniques in a significant fraction (approximately 10%) of chronic lymphocytic leukemia (CLL). However, there have been no reports describing the presence of cytogenetic 18;22 and 2;18 translocations in CLL, in spite of extensive karyotypic studies. We present here two cases of CLL, one with cytogenetically detected t(2;18)(p11;q21) and the other with the t(18;22)(q21;q11). The molecular analysis revealed that these translocations juxtaposed the bcl-2 and immunoglobulin light-chain (IgL) genes. The t(18;22) broke the 5' flanking region of the bcl-2 gene and juxtaposed to the immunoglobulin lambda light-chain (Ig lambda) gene in a head-to-head configuration, as in the cases previously described. In the case of the t(2;18), the bcl-2 gene and immunoglobulin kappa light-chain (Ig kappa) gene were juxtaposed in a head-to-tail configuration, which is opposite to that expected from the orientation of the genes on chromosomes. The breakpoint was located within the 5' untranslated region of the bcl-2 gene. The results presented here indicate that the bcl-2/immunoglobulin light-chain (IgL) gene juxtaposition seen in a fraction of CLL is the result of cytogenetically detectable reciprocal chromosome translocations 2;18 and 18;22.

Base Sequence↗
PubMed1992

[Clinical evaluation of bone marrow fibrosis in non-Hodgkin's lymphomas].

A study was performed in 62 patients with non-Hodgkin's lymphoma (ATL included) who were hospitalized between 1985 and 1991 and who underwent bone marrow aspiration and biopsy before or after treatment or at the time of recurrence. The relationships between the extent of bone marrow fibrosis and other prognostic factors as well as the effects of chemotherapy and bone marrow fibrositic prognosis were examined. The results were as follows: 1) The periods of survival in patients with high degree of fibrosis in bone marrow were significantly shortened. 2) The extent of bone marrow fibrosis significantly correlated with the presence or general symptoms, bone marrow invasion, and blood levels of LDH and Ca on blood biochemical examinations. 3) Effective therapy reduced collagen fibers as well as reticulin fibers in bone marrow. 4) Sixty-four percent of relapsing cases showed increase of bone marrow fibrosis. These results suggest that understanding the state of bone marrow fibrosis over the clinical course may give a good guide of indication the prognosis of malignant lymphoma.

Bone Marrow↗
PubMed1992

Development of a non-invasive transcutaneous blood glucose monitoring method using an ISFET biosensor.

A transcutaneous blood glucose monitoring method has been developed by combining an SOS/ISFET (silicone-on-sapphire/ion sensitive field effect transistor) biosensor with an SEF (suction effusion fluid) collecting technique. The SEF collecting cell has a stainless steel mesh at its bottom which is kept in a weak vacuum condition so as to suck up transcutaneous SEF and deposit it in a reservoir above. An ISFET biosensor, consisting of immobilized enzyme membranes, enables the detection of glucose concentrations in very small samples. The method has been successfully applied to non-invasive monitoring of human blood glucose levels during tests involving 75 g OGTT (oral glucose tolerance test). Glucose concentrations measured with SEF showed good correlation with those obtained directly from serum. Results suggest the feasibility of a portable blood monitoring system.

Biosensing Techniques↗
PubMed1992

[Thoracoscopic laser coagulation shrinkage of blebs in the treatment of spontaneous pneumothorax].

As a thoracoscopic treatment for spontaneous pneumothorax, electrocautery has been mainly used. But contact type electrocautery has a risk of perforation of blebs. We adopted carbon monoxide laser (wave length 5.4 microns) and good coagulation shrinkage of blebs could be obtained by non-contact irradiation. CO laser was delivered by As-S glass fiber and power of fiber tip was 2-4 W. Compared with Nd-YAG laser (wavelength 1.06 microns), CO laser showed lower risk of perforation of blebs. Thoracoscopic CO laser coagulation shrinkage of blebs proved to be a important method of treatment for patient of spontaneous pneumothorax.

Humans↗
PubMed1991

The role of N-glycosylation of GLUT1 for glucose transport activity.

To elucidate a functional role of N-glycosylation in glucose transporters, we introduced oligonucleotide-directed mutagenesis in GLUT1 cDNA to remove the possible site for N-linked glycosylation. The wild-type and the mutated GLUT1 cDNAs which induced a mutation of Asn at residue 45 to Asp, Tyr, or Gln were transfected and stably expressed into Chinese hamster ovary cells. The expressed wild-type and the mutated GLUT1 was demonstrated to be a broad band of a 45-60-kDa form and a sharp band of a 38-kDa form on Western blot analysis, respectively, indicating no glycosylation in the mutated GLUT1. Although the cell surface labeling of the glucose transporters demonstrated the presence of the glycosylation-defective glucose transporters on the cells surface, photoaffinity labeling of glycosylation-defective GLUT1 with [3H] cytochalasin B and a photoreactive mannose derivative, [3H]2-N-4-(1-azi-2,2,2,trifluoroethyl)benzoyl-1,3-bis(D-mannos+ ++-4-yloxy)-2- propylamine in the membranes was observed to be 40-70 and 15-30% of that of the wild-type GLUT1, respectively. The kinetic study of 2-deoxyglucose uptake revealed that the glycosylation-defective GLUT1 had a 2-2.5-fold greater Km value for 2-deoxyglucose uptake compared with the wild-type GLUT1. These observations strongly suggest that 1) N-glycosylation of GLUT1 glucose transporter is only on Asn 45 and 2) N-glycosylation plays an important role in maintaining a structure of glucose transporter with high affinity for glucose, thus, with high transport activity.

Affinity Labels↗
PubMed1991

Crystal structures of the apo- and holomutant human lysozymes with an introduced Ca2+ binding site.

The three-dimensional structures of apo- and holomutant human lysozymes (D86/92 lysozyme), in which a calcium binding site was designed and created for enhancing molecular stability by replacing both Gln86 and Ala92 with aspartic acids, were refined at 1.8-A resolution by x-ray crystallography. The overall structures and crystallographic thermal factors of all three proteins, the apo-, holo-D86/92, and the wild-type human lysozymes, were essentially identical; these results showed that the introduction of the calcium binding site did not affect either the overall structure or molecular rigidity of the proteins. However, structure analyses of the apo-D86/92 lysozyme revealed that the mutations affected the side chain conformation of residue 86 and hydrogen networks between the protein and the internal solvent molecules. In the structure of the holo-D86/92 lysozyme, seven oxygen ligands formed a slightly distorted pentagonal bipyramid around the calcium ion, indicating that the coordination around the calcium ion was quite similar to that in baboon alpha-lactalbumin. The pentagonal bipyramid coordination could be one of the most widely found and appropriate calcium binding schemes in proteins.

Apoproteins↗
PubMed1991

Alteration of N-terminal residues of mature human lysozyme affects its secretion in yeast and translocation into canine microsomal vesicles.

Signal sequences play a central role in the initial membrane translocation of secretory proteins. Their functions depend on factors such as hydrophobicity and conformation of the signal sequences themselves. However, some characteristics of mature proteins, especially those of the N-terminal region, might also affect the function of the signal sequences. To examine this possibility, several mutants of human lysozyme modified in the N-terminal region of the mature protein were constructed, and their secretion in yeast as well as in vitro translocation into canine pancreatic microsomes were analyzed using an idealized signal sequence L8 (MR(L)8PLAALG). Our results show the following. (1) Change in the charge at the N-terminal residue of the mature protein does not affect secretion drastically. (2) Substitution of a proline residue at the N terminus prevents cleavage of the signal sequence, although translocation itself is not impaired. (3) Excessive positive charges in the N-terminal region delay translocation of the precursor protein across the membrane. (4) Polar and negatively charged residues introduced into the N-terminal region affect the secretion of the mature protein by preventing its correct folding.

Amino Acid Sequence↗
PubMed1991

High-level secretion of the extracellular domain of the human growth hormone receptor using a baculovirus system.

A chemically synthesized gene (hGHR-ED) coding for the extracellular domain (ED) of the human growth hormone (hGH) receptor (hGHR) was inserted into the genome of Autographa californica nuclear polyhedrosis virus adjacent to the polyhedrin promoter. Spodoptera frugiperda cells infected with the recombinant virus secreted a protein with hGH-binding activity into the medium. The secreted 35-kDa protein was purified to near homogeneity. The purified protein exhibited a high binding affinity (Kd = 0.2-0.3 nM) to hGH. The highest cell production capability was estimated at more than 10-20 micrograms hGHR-ED/ml of culture. The inhibition of the hGHR-ED secretion by treatment with tunicamycin suggests that glycosylation is important for secretion.

Amino Acid Sequence↗
PubMed1991

Effects of proline mutations on the unfolding and refolding of human lysozyme: the slow refolding kinetic phase does not result from proline cis-trans isomerization.

The unfolding and refolding kinetics of six proline mutants of the human lysozyme (h-lysozyme) were carried out and compared to that of the wild-type protein. Our results show that the slow refolding phase observed in the h-lysozyme refolding kinetics cannot be ascribed to proline isomerization reactions. The h-lysozyme contains two proline residues at positions 71 and 103, both in the trans conformation in the native state. The refolding kinetics of the P71G/P103G mutant, in which both prolines have been replaced by a glycine, were found to be similar to those of the wild-type protein. The same slow phase amplitude of about 10% was found for both proteins, and the slow phase rate constants were also identical within experimental error. Other mutants such as P103G or P71G, in which only one of the two prolines has been replaced by a glycine, and A47P with its three prolines, gave identical slow refolding phases. The X-ray structure analysis and scanning microcalorimetric study of each protein (Herning et al., unpublished experiments) have confirmed that none of the considered mutations affects significantly protein structure and that no major changes in protein stability were brought about by these mutations. Therefore, comparison of the properties of the mutant and wild-type proteins is legitimate. Interestingly, the refolding kinetics of the V110P mutant, in which a proline residue has been introduced at position 110 (N-terminus of an alpha-helix), were clearly triphasic. For this mutant an additional very slow phase with properties similar to those expected from the proline hypothesis was detected. Equilibrium denaturation studies were conducted for each protein, and the refolding pathway of h-lysozyme is partly presented. We also discuss the effect of proline mutations on the energetics of the folding pathway of the h-lysozyme in water.

Base Sequence↗
PubMed1991

[The management of stage I lymphomas of the B-cell type with special reference to the role of radiation therapy].

Fifty-one patients with clinical stage I B-cell lymphomas were treated between 1980 and 1988. For the entire group, the actuarial 5-year survival rate and 5-year freedom from relapse rate were 78% and 64%, respectively. Primary site, tumor bulk and performance status were the prognostic factors. Twenty-three patients were intensively treated with local radiotherapy alone, because (1) they had histologically low grade (7 patients) or follicular large cell (1 patients) tumors, (2) Waldeyer's ring was the site of the primary (11 patients) or (3) the tumor was less than 4 cm in maximum diameter (4 patients). Among them, only one patient died due to lymphoma (5-year survival rate: 95%), and 19 remained disease free (5-year freedom from relapse rate: 80%). In contrast, of the remaining 23 patients treated with both radiation therapy and combination chemotherapy (VEMP or CHOP), the 5-year survival rate and 5-year freedom from relapse rate were 70% and 54%, respectively. These results suggest that high-risk patients should be treated with more aggressive combination chemotherapy as well as radiotherapy. However, low-risk patients with stage I B-cell lymphomas can be treated by local radiotherapy alone.

Adult↗
PubMed1991

Hydrolysis of branched cyclodextrins by a cyclodextrin-hydrolyzing enzyme from Bacillus sphaericus E-244.

The action of a cyclodextrin-hydrolyzing enzyme from Bacillus sphaericus E-244 on branched alpha- and beta-cyclodextrins was investigated. Glucosyl-alpha-cyclodextrin (6-O-alpha-D-glucosylcyclomaltohexaose) and maltosyl-alpha-cyclodextrin (6-O-alpha-D-maltosylcyclomaltohexaose) were hydrolyzed to 6(3)-O-alpha-D-glucosylmaltohexaose and 6(3)-O-alpha-D-maltosylmaltohexaose, respectively. Glucosyl-beta-cyclodextrin (6-O-alpha-D-glucosylcyclomaltoheptose) and maltosyl-beta-cyclodextrin (6-O-alpha-D-maltosyclomaltohepatose) were also mainly transformed to 6(4)-O-alpha-D-glucosylmaltoheptaose and 6(4)-O-alpha-D-maltosylmaltoheptaose, respectively. These results suggest that the cyclodextrin-hydrolyzing enzyme cleaves branched alpha- and beta-cyclodextrins at an alpha-1,4 linkage which is located furthest from the branching point on the cyclodextrin ring.

Bacillus↗
PubMed1991

Defective provirus form of human T-cell leukemia virus type I in adult T-cell leukemia/lymphoma: clinicopathological features.

Human T-cell leukemia virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma (ATLL). To examine the relationship between defective HTLV-I proviruses and clinicopathological features, we examined 95 patients with ATLL showing clonal integration of HTLV-I proviral DNA; 77 patients (81%) showed 1 clonal band, 15 (16%) showed 2 clonal bands, and 3 (3%) showed 3 clonal bands. In addition, the defective proviral form was detected in 28 patients (29%): 23 (30%) of the 77 with 1 clonal band, 4(27%) of the 15 with 2 clonal bands, and 1(33%) of the 3 with 3 clonal bands. The numbers of clonal bands had no association with the presence of defective proviruses. We classified the 95 patients with ATLL into four types according to clinicopathological features (smoldering leukemia, chronic leukemia, acute leukemia, and lymphoma types). The distribution of patients with the defective form was not different among these four types. The HTLV-I genomes must have integrated into the human genome DNA and been deleted partially in the cells. The defective form was kept during the clinical stage. All patients with the defective form showed defect of the gag or/and env region. No patient had a defect of the pX region. These data suggest that the pX region of HTLV-I must have played an important role in ATLL genesis.

Amino Acid Sequence↗
PubMed1991

The crystal structure of a mutant human lysozyme C77/95A with increased secretion efficiency in yeast.

The three-dimensional structure of a mutant human lysozyme, C77/95A, in which residues Cys77 and Cys95 were replaced by alanine, was determined at 1.8-A resolution by x-ray crystallography. The properties of this mutant protein have been well characterized with respect to its thermal stability and secretion efficiency in a yeast expression system. The overall three-dimensional structure of C77/95A was found to be essentially identical to that of the wild-type human lysozyme, although the coordinates were shifted by more than 0.5 A and the thermal factors of the main-chain atoms were increased in the vicinity of residue 77. The reduction in thermal stability of this mutant has been previously explained by an increase in entropy of the unfolded state. In addition, a packing defect (cavity) produced by the removal of the disulfide bond was detected in the three-dimensional structure of C77/95A. This cavity can also be a reason why the stability of the protein is reduced because the free energy of the folded state could be expected to increase. The increased secretion efficiency cannot be due mainly to the three-dimensional structure, but may possibly be related to some event in the pathway of protein secretion. One of the possibilities might involve molecular flexibilities in the secondary or tertiary structure for lack of one of the disulfide bonds.

Alanine↗
PubMed1991

Behavior of cysteine mutants of human lysozyme in de novo synthesis and in vivo secretion.

To investigate the mechanism of disulfide-bond-coupled de novo folding of human lysozyme, we have constructed 23 mutant enzymes in which cysteine residue(s) were replaced by alanine(s). The mutant genes were translated in vitro in a system composed of rabbit reticulocyte lysate, canine pancreatic microsomal vesicles and oxidized glutathione. This system allows the formation of intramolecular disulfide bonds in translation products translocated into the microsomal lumen. The mobilities of the translation products were analyzed by SDS/PAGE in nonreducing conditions. Some mutant lysozymes were found to form a compact conformation with native-like mobility in the presence of SDS. The de novo formation of the SDS-resistant compact conformation of each mutant correlated well with its efficiency of secretion by Saccharomyces cerevisiae. Our results suggest that the de novo synthesized products reflect the conformational states in vivo to some extent, and that the formation of SDS-resistant compact conformation can be regarded as a necessary condition for allowing lysozyme to be secreted. In addition, the analysis of a mutant C116A (Cys116----Ala) under different oxidative conditions suggests two distinct pathways for the disulfide-bond-coupled formation of the compact conformation.

Animals↗
PubMed1991

A T-cell neoplasia showing clinicopathologic features of malignant histiocytosis with novel chromosomal abnormalities and N-ras mutation.

Malignant histiocytosis (MH) is a distinct disease entity defined clinically and morphologically. However, the neoplastic origin of MH is not well established. The authors report a 26-year-old woman who showed the typical clinicopathologic features of so-called MH. Cytogenetic and molecular genetic examinations were performed in addition to the morphologic and immunologic approach. The expression of CD2 and T-cell receptor gene rearrangements indicated the T-cell origin of this case. CD30, which is positive for anaplastic large cell lymphoma (Ki-1 lymphoma), was not expressed. The cytogenetic study revealed a clonal chromosome abnormality involving 3q25, 6p21, 11p15, and 11q21. An N-ras point mutation within codon 12 (GGT----GCT) was also detected. These finding indicate that MH defined clinically and morphologically is not a tumor of true histiocytic origin and that it should be reclassified on the basis of immunologic, cytogenetic, and molecular genetic data.

Adult↗
PubMed1991

Evidence for intramolecular disulfide bond shuffling in the folding of mutant human lysozyme.

Our previous results using the Saccharomyces cerevisiae secretion system suggest that intramolecular exchange of disulfide bonds occurs in the folding pathway of human lysozyme in vivo (Taniyama, Y., Yamamoto, Y., Kuroki, R., and Kikuchi, M. (1990) J. Biol. Chem. 265, 7570-7575). Here we report on the results of introducing an artificial disulfide bond in mutants with 2 cysteine residues substituting for Ala83 and Asp91. The mutant (C83/91) protein was not detected in the culture medium of the yeast, probably because of incorrect folding. Thereupon, 2 cysteine residues Cys77 and Cys95 were replaced with Ala in the mutant C83/91, because a native disulfide bond Cys77-Cys95 was found not necessary for correct folding in vivo (Taniyama, Y., Yamamoto, Y., Nakao, M., Kikuchi, M., and Ikehara, M. (1988) Biochem. Biophys. Res. Commun. 152, 962-967). The resultant mutant (AC83/91) was secreted as two proteins (AC83/91-a and AC83/91-b) with different specific activities. Amino acid and peptide mapping analyses showed that two glutathiones appeared to be attached to the thiol groups of the cysteine residues introduced into AC83/91-a and that four disulfide bonds including an artificial disulfide bond existed in the AC83/91-b molecule. The presence of cysteine residues modified with glutathione may indicate that the non-native disulfide bond Cys83-Cys91 is not so easily formed as a native disulfide bond. These results suggest that the introduction of Cys83 and Cys91 may act to suppress the process of native disulfide bond formation through disulfide bond interchange in the folding of human lysozyme.

Amino Acid Sequence↗