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M Kikuchi

Publications and source records attributed to M Kikuchi.

At least 667 records · Page 37Linked to original sources
PubMed1993

[Clinicopathological evaluation and treatment of bucillamine induced membranous nephropathy].

We discussed clinicopathological evaluation and treatment of bucillamine induced renal destruction. Thirteen cases of rheumatoid arthritis were investigated in whom proteinuria had developed while being treated with bucillamine. The dose of bucillamine ranged from 100 to 300 mg/day, and many of them were treated with a dose of 200-300 mg/day. The total dose was in the range of 9-57 g. Proteinuria had developed within 3 months after perceiving the efficacy of bucillamine in many of the cases. The details of renal histology revealed that membranous nephropathy was noted in all of the 13 cases and that mesangial proliferative gromerulonephritis was noted in eight cases (61.5%), thin basement membrane was noted in four cases (30.8%) and in one case (7.7%) amyloidosis were identified in parallel. After suspending further administration of bucillamine, the proteinuria was gradually reduced without any specific treatment or without increase in the dose of corticosteroid, and was eliminated in all cases within 10 months. There were some cases in whom proteinuria was eliminated within a short period of time by the administration of corticosteroid in a moderate dose (prednisolone 30 mg/day). It is necessary to initiate the administration of bucillamine from a small dose such as 100 mg/day and pay attention to onset of any side effect. It was also seemed necessary to confirm the renal histology by renal biopsy as far as feasible because a large variety of pathological findings are developed in the kidney of these cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[Spontaneous remission in adult T-cell leukemia].

Spontaneous remission in a 50-year-old woman with adult T-cell leukemia (ATL) is presented. The patient was referred to our hospital because of generalized lymphadenopathy and the appearance of abnormal lymphocytes with convoluted nuclei in the peripheral blood. She was diagnosed as ATL because of the characteristic morphological ATL cells, cell surface marker analysis and the presence of serum antibody to human T-cell lymphotropic virus type-I (HTLV-I). However during the following weeks before admission, her leukocyte count and ATL cells in the peripheral blood decreased in number even though she received no therapy. After admission, abnormal lymphocytes in the peripheral blood disappeared and lymphadenopathy decreased in size, LDH level was normalized. Spontaneous remission had continued ten months without chemotherapy, but she developed recurrence thereafter and died two years later after onset with progressive disease. Gene analysis study by Southern blot analysis showed monoclonal integration of HTLV-I proviral DNA at the same positions both before regression and after recurrence. In this case, the trigger of spontaneous remission was unclear.

Female↗
PubMed1993

[Analysis of blood flow velocity in the ophthalmic artery by color Doppler imaging. 2. Studies on diabetic eyes].

Color Doppler imaging was used to investigate the changes in Pourcelot index (RI), which is an index for vascular resistance calculated from the blood flow velocity of the ophthalmic artery, related to the complications of diabetes mellitus (diabetic retinopathy, diabetic nephropathy) and systemic background (duration of diabetes mellitus, value of hemoglobin A1C (HbA1c)) in 46 diabetic patients and in 20 normal subjects. RI was significantly higher in diabetic patients than in normal subjects (p < 0.05). RI increased in patients without retinopathy (p < 0.05), in patients with background retinopathy (p < 0.05), and in patients with preproliferative or proliferative retinopathy (p < 0.05), but it did not change in patients after panretinal photocoagulation, compared with the normal subjects. In diabetic patients, RI was higher (p < 0.05) in patients with nephropathy than in those without nephropathy. The time from onset of diabetes mellitus and the value of HbA1c had no correlation with RI. Our results indicate that choroidal circulation was changed in diabetic patients compared with normal subjects and that the changes were related to diabetic nephropathy.

Aged↗
PubMed1993

[Changes of the diabetic retinopathy score].

Changes of the retinopathy score with the progression of diabetic retinopathy were investigated in 87 eyes of 44 diabetic patients. The previously reported retinopathy scoring system of Yamashita et al., utilizing fluorescein angiography, was used. Factors relevant to an increase of the retinopathy score were determined using quantification analysis (a type of multivariate analysis). The factors assessed were microaneurysms, the extent of retinal nonperfusion, intraretinal microvascular abnormalities, the grade of fluorescein dye leakage from retinal vessels, neovascularization, the grade of macular edema, the HbA1c level and the duration of retinopathy. The retinopathy score increased in 50 eyes (57%) after a mean follow-up period of 24.9 months. The probability of the score increasing in the eyes with advanced background retinopathy was 78%. The probability in eyes with preproliferative or proliferative diabetic retinopathy was 52% or 11%, respectively. The mean increase of the score in one year was 3.0 for all subjects. The increase in the eyes with advanced background, preproliferative or proliferative diabetic retinopathy was 6.1, 2.8 or 0.1, respectively. Our results suggest that this scoring system can effectively detect changes of background and preproliferative retinopathy. According to quantification analysis, the factor most relevant to the increase of the score was retinal nonperfusion. Dye leakage and neovascularization were also relevant, in descending order.

Diabetic Retinopathy↗
PubMed1993

Mixed connective tissue disease associated with lupus lymphadenitis.

We have encountered 2 patients with mixed connective tissue disease (MCTD) associated with lymphadenopathy at the outset. Biopsy specimens of enlarged lymph nodes showed massive necrotizing lesions with follicular hyperplasia, which are occasionally observed in the involved lymph nodes of patients with systemic lupus erythematosus (SLE) and called lupus lymphadenitis. Usually, the only histologic finding of an involved lymph node in MCTD is lymphoid hyperplasia. These are the 2nd and 3rd cases of MCTD associated with lupus lymphadenitis. Our cases suggest that histologic studies of the swollen lymph nodes are not helpful in distinguishing MCTD from SLE.

Biopsy↗
PubMed1993

[Lymphoscintigraphy with 99mTc-DTPA-HSA in the diagnosis of protein-losing gastroenteropathy].

We evaluated the diagnostic capability of technetium-99m-diethylene triamine pentaacetic acid-human serum albumin (99mTc-DTPA-HSA) lymphoscintigrapy in a patient with protein-losing gastroenteropathy. 99mTc-DTPA-HSA (total 740 MBq) was injected subcutaneously into the digital webs of the both feet. With a gamma camera, whole-body and abdominal lymphoscintigrams were obtained after the injection of the radioisotope: early images and delayed images taken 5-15 min and 50-60 min, respectively, after the injection. A few days later, the dynamic lymphoscintigraphy was also performed. Lymph fluid leakage into the small bowel and the sites of the leakage were detected. It was concluded that lymphoscintigraphy with 99mTc-DTPA-HSA was a useful diagnostic tool in patients with protein-losing gastroenteropathy.

Adult↗
PubMed1993

[Technological progress in hyperthermia].

In the early stage of hyperthermia, a large number of physical and engineering efforts have been done in the development or the improvement of the heating techniques. As matters stand, they were not always satisfied clinically. Thus even in this moment, clinical techniques of hyperthermia should be build up rapidly. This paper describes some of the highlights of ongoing physical researches to develop the clinical hyperthermia and to identify a trend of emerging physical systems available on hyperthermia.

Humans↗
PubMed1993

[Analysis of blood flow velocity of ophthalmic artery with color Doppler imaging. 1. Studies on normal human eyes].

Color Doppler imaging was used to analyze the blood flow velocity of the ophthalmic artery (BVA) by measuring the pulse wave of flow velocity in the ophthalmic artery of normal subjects. Maximum systolic BVA (Vmax), minimum end-diastolic BVA (Vmin), time-averaged BVA (Vmean), Pourcelot index (RI) and pulsatility index (PI) were determined using color Doppler imaging. The coefficients of reproducibility of Vmax, Vmin, Vmean, RI and PI were 10%, 9%, 15%, 4% and 14%, respectively, when analyzed twice at one-hour intervals. There was no significant difference between the values of the right eye and that of the left eye in each case. The averages of Vmax, Vmin, Vmean, RI and PI of 33 normal eyes were 25.4 +/- 7.6 cm/sec, 6.3 +/- 2.3 cm/sec 16.7 +/- 6.6 cm/sec, 0.75 +/- 0.052, 1.19 +/- 0.25 (mean +/- S.D.), respectively, Vmax, Vmin and Vmean decreased significantly with age (Vmax:linear correlation coefficient r = -0.65, p < 0.001; Vmin: r = -0.61, p < 0.001, r = -0.64, p < 0.001. RI did not change with age. PI increased significantly with age (r = 0.30, p < 0.05).

Adult↗
PubMed1992

Non-lysosomal degradation of misfolded human lysozymes with and without an asparagine-linked glycosylation site.

Human lysozyme is a monomeric secretory protein composed of 130 amino acid residues, with four intramolecular disulfide bonds and no oligosaccharides. In this study, a mutant protein, [Ala128] lysozyme, which cannot fold because it lacks a disulfide bond, Cys6-Cys128, was expressed in mouse fibroblasts and was found to be mostly degraded in the cells, whereas the control wild-type lysozyme was quantitatively secreted into the media. The degradation of [Ala128]lysozyme was independent of the transport from the endoplasmic reticulum to the Golgi apparatus. The degradation was greatly inhibited by incubation of cells at 15 degrees C, but was minimally affected by treatment of cells with the lysosomotropic agent, chloroquine, implying a non-lysosomal process. Additional mutations (Gly48-->Ser or Met29-->Thr) were created to make asparagine-linked (N-linked) glycosylation site in the [Ala128]lysozyme, and the resultant double mutants, [Ser48, Ala128]lysozyme and [Thr29, Ala128]lysozyme, were analyzed with respect to their intracellular degradation. These mutant proteins were susceptible to N-linked glycosylation, and were degraded in a similar manner to that of [Ala128] lysozyme, except that the onset of degradation of [Ser48, Ala128]lysozyme and [Thr29, Ala128] lysozyme, but not of [Ala128]lysozyme, was preceded by a lag period of up to 60 min. Furthermore, the degradative double mutants, [Ser48, Ala128]lysozyme and [Thr29, Ala128]lysozyme, were glycosylated post-translationally as well as co-translationally. These observations suggest that there is some interaction between the mechanisms of glycosylation and degradation.

Animals↗
PubMed1992

Nonsense mutation of glucokinase gene in late-onset non-insulin-dependent diabetes mellitus.

A nonsense mutation at codon 186 in exon 5 of the gene for glucokinase, an enzyme important for glucose-induced insulin secretion, was identified in a Japanese patient with late-onset non-insulin-dependent diabetes mellitus (NIDDM). All affected members of her family were heterozygous for the mutation and had late-onset NIDDM or impaired glucose tolerance, whereas unaffected members showed normal glucose tolerance. The early insulin response to oral glucose was impaired in affected relatives, but was normal in those unaffected. These findings suggest that the glucokinase mutation raises the set-point of pancreatic beta cells for glucose-induced insulin secretion, leading to abnormal glucose tolerance in some patients with late-onset NIDDM.

Adolescent↗
PubMed1992

Replacement of intracellular C-terminal domain of GLUT1 glucose transporter with that of GLUT2 increases Vmax and Km of transport activity.

The intracellular C-terminal domain is diverse in size and amino acid sequence among facilitative glucose transporter isoforms. The characteristics of glucose transport are also divergent, and GLUT2 has far higher Km and Vmax values compared with GLUT1. To investigate the role of the intracellular C-terminal domain in glucose transport, we expressed in Chinese hamster ovary cells the mutated GLUT1 protein whose intracellular C-terminal domain was replaced with that of GLUT2 by means of engineering the chimeric cDNA. Cytochalasin B, for which GLUT2 protein has much lower affinity, bound to this chimeric protein in a fashion similar to GLUT1. In contrast, greater transport activity was observed in this chimeric glucose transporter compared with the wild-type GLUT1 at 10 mM 2-deoxy-D-glucose concentration. The kinetic studies on 2-deoxy-D-glucose uptake revealed a 3.8-fold increase in Km and a 4.3-fold increase in Vmax in this chimeric glucose transporter compared with the wild-type GLUT1. Thus, replacement of the intracellular C-terminal domain confers the GLUT2-like property on the glucose transporter. These results strongly suggest that the diversity of intracellular C-terminal domain contributes to the diversity of glucose transport characteristics among isoforms.

Amino Acid Sequence↗
PubMed1992

Conformation and length of the signal sequence affect processing of secretory protein.

Processing of human lysozyme with artificially designed signal sequences was examined in an in vitro translation-translocation system and compared with their secretory capabilities in yeast. It has been shown that the conformation of the C-terminal region of the signal sequence and the length of the hydrophobic segment are important factors for efficient cleavage of the signal sequence.

Amino Acid Sequence↗
PubMed1992

Role of the basic amino acid cluster and Glu-23 in pyrimidine dimer glycosylase activity of T4 endonuclease V.

T4 endonuclease V [endodeoxyribonuclease (pyrimidine dimer); deoxyribonuclease (pyrimidine dimer), EC 3.1.25.1] initiates repair of damaged DNA by hydrolysis of the N-glycosyl bond at the 5' side of a pyrimidine photodimer in double-stranded DNA. To study one of the active sites of T4 endonuclease V, systematic site-directed mutagenesis was performed on the synthetic T4 endonuclease V gene, in parallel with three-dimensional structure analysis by x-ray crystallography. The mutant proteins were evaluated for DNA glycosylase activity using an oligonucleotide duplex (14-mer) containing a single thymidine dimer as a substrate. Replacement of either Glu-23 with glutamine or asparatic acid or Arg-3 with glutamine completely abolished DNA glycosylase activity. Mutation of Arg-3 to lysine or of Arg-26 to glutamine or lysine in a basic amino acid cluster caused serious defects in DNA glycosylase activity, which are reflected in the increases in Km and decreases in kcat of DNA glycosylase activity. On the other hand, substitutions of lysine for Arg-22 or of glutamine for Arg-117 or Lys-121 resulted in increases in the Km value. The completely inactive mutant proteins, E23Q and R3Q, in which glutamine was substituted for Glu-23 and Arg-3, respectively, were further investigated by CD spectroscopy for their ability to bind the oligonucleotide substrate. It was found that the E23Q protein retained specific substrate-binding ability, whereas the R3Q protein did not. These results indicate that Glu-23 plays an important role in catalysis of the DNA glycosylase reaction, and that Arg-3 is a crucial residue for substrate binding. In addition, Arg-22, Arg-26, Arg-117, and Lys-121 in the basic amino acid cluster also participate in substrate binding. We conclude that the basic amino acid cluster in T4 endonuclease V is an essential structure for DNA glycosylase activity.

Amino Acid Sequence↗
PubMed1992

Participation of glutamic acid 23 of T4 endonuclease V in the beta-elimination reaction of an abasic site in a synthetic duplex DNA.

T4 endonuclease V catalyzes the hydrolysis of the glycosyl bond of a thymine dimer in a DNA duplex and the cleavage of the 3'-phosphate by beta-elimination. We have previously identified a catalytic site for the first reaction (pyrimidine dimer-glycosylase activity) by systematic mutagenesis (Doi et al. Proc. Natl. Acad. Sci. USA 1992 in press) and by x-ray crystallography (Morikawa et al. Science, 256: 523-526, 1992). The results showed that replacement of Glu23 with either glutamine or aspartic acid completely abolished the glycosylase activity. We describe the investigation of the second reaction (apurinic/apyrimidinic endonuclease activity), using twenty two mutants of T4 endonuclease V plus a DNA mini duplex containing an abasic site. Replacement of Glu23 by glutamine abolished the second reaction, but replacement with aspartic acid did not. The pH optima of the mutant (23 Asp) and the wild type were found to be 5.0 and 5.5, respectively. We conclude that the carboxylate anion in position 23 may act as a general base in the beta-elimination reaction of the endonuclease.

Amino Acid Sequence↗
PubMed1992

Functional signal peptide reduces bilayer thickness of phosphatidylcholine liposomes.

To investigate the interaction between a signal peptide and the lipid bilayer, two kinds of peptides, L8-M5 (L8 = MRL8PLAALG, M5 = KVFER) and L14-M5 (L14 = MRL14PLAALG), were examined in membranes composed of dioleoylphosphatidylcholine (DOPC). Peptides L8 and L14 are artificially designed signal sequences, and M5 is the N-terminal five residues of human lysozyme; L8 mediated effective secretion of human lysozyme in yeast, while L14 did not [Yamamoto, Y., et al. (1987) Biochem. Biophys. Res. Commun. 149, 431-436]. DOPC liposomes incorporating L8-M5 or L14-M5 were observed by electron cryomicroscopy as pairs of concentric circles, and the separation of the bilayer was measured along the membrane. Peptide L8-M5 was found to reduce the bilayer thickness, but L14-M5 did not. CD measurements revealed that L8-M5 adopted an alpha-helical conformation with random coil in the liposome membranes and that L14-M5 adopted a more helical and less random conformation than L8-M5. Fluorescence spectroscopy using both aqueous and membranous probes revealed that L8-M5 destabilized the lipid bilayer more strongly than L14-M5. These results suggest that functional L8-M5 reduces the bilayer thickness and destabilizes the lipid bilayer and that these activities are important for signal peptide function.

Amino Acid Sequence↗
PubMed1992

Enthalpic destabilization of a mutant human lysozyme lacking a disulfide bridge between cysteine-77 and cysteine-95.

To understand the role of disulfide bridges in protein stability, the thermodynamic changes in the denaturation of two mutant human lysozymes lacking a disulfide bridge between Cys-77 and Cys-95 (C77A and C77/95A) were analyzed using differential scanning calorimetry (DSC). At pH 3.0 and 57 degrees C, the stabilities of both the C77A and C77/95A mutants were decreased about 4.6 kcal.mol-1 in Gibbs free energy change. Under the same conditions, the enthalpy changes (delta H) were 94.8 and 90.8 kcal.mol-1, respectively, which were smaller than that of the wild type (100.8 kcal.mol-1). The destabilization of the mutants was caused by enthalpic factors. Although X-ray crystallography indicated that the mutants preserve the wild-type tertiary structure, removal of the disulfide bridge increased the flexibility of the native state of the mutants. This was indicated both by an increase in the crystallographic thermal factors (B-factors) and by a decrease in the affinity of N-acetylglucosamine trimer [(NAG)3] observed using isothermal titration calorimetry (DTC) due to entropic effects. Thus, the effect of cross-linking on the stability of a protein is not solely explained by the entropy change in denaturation.

Amino Acid Sequence↗
PubMed1992

Role of proline residues in human lysozyme stability: a scanning calorimetric study combined with X-ray structure analysis of proline mutants.

It has been shown that protein stability can be modulated from site-directed mutations that affect the entropy of protein unfolding [Matthews, B. W., Nicholson, H., & Becktel, W. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 6663-6667]. However, the effect of a specific amino acid replacement on stability highly depends on the location of the mutation site and its environment in the protein structure [Yutani, K., Hayashi, S., Sugisaki, Y., & Ogasahara, K. (1991) Proteins Struct., Funct., Genet. 9, 90-98). To clarify the role of specific proline residues in the thermostability of human lysozyme (h-lysozyme), a series of proline mutants were investigated by means of scanning calorimetry and high-resolution X-ray crystallography. The thermodynamic properties of the mutant and wild-type h-lysozymes are compared and discussed on the basis of their three-dimensional structure. h-Lysozyme contains two proline residues at positions 71 and 103. The Pro71----Gly substitution was found to destabilize h-lysozyme by decreasing the entropic contribution of unfolding by about 2 kcal/mol at 68.8 degrees C. This is consistent with the theoretical expectations for such a substitution. However, the same substitution at position 103 (Pro103----Gly) does not affect h-lysozyme stability, and the thermodynamic properties of the P71G/P103G and P71G mutants are essentially the same. Pro71 which is conserved among lysozymes from other species, appears to be important for stability, whereas Pro103, which is not conserved, does not. These differences are explained in terms of residue accessibility to the solvent and crystallographic B-factor, which reflects the amino acid mobility.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry, Differential Scanning↗