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Biomedical subjects

M Ikeuchi

Publications and source records attributed to M Ikeuchi.

At least 19 recordsLinked to original sources
PubMed1995

Directed inactivation of the psbI gene does not affect photosystem II in the cyanobacterium Synechocystis sp. PCC 6803.

PsbI is a small, integral membrane protein component of photosystem II (PSII), a pigment-protein complex in cyanobacteria, algae and higher plants. To understand the function of this protein, we have isolated the psbI gene from the unicellular cyanobacterium Synechocystis sp. PCC 6803 and determined its nucleotide sequence. Using an antibiotic-resistance cartridge to disrupt and replace the psbI gene, we have created mutants of Synechocystis 6803 that lack the PsbI protein. Analysis of these mutants revealed that absence of the PsbI protein results in a 25-30% loss of PSII activity. However, other PSII polypeptides are present in near wild-type amounts, indicating that no significant destabilization of the PSII complex has occurred. These results contrast with recently reported data indicating that PsbI-deficient mutants of the eukaryotic alga Chlamydomonas reinhardtii are highly light-sensitive and have a significantly lower (80-90%) titer of the PSII complex. In Synechocystis 6803, PsbI-deficient cells appear to be slightly more photosensitive than wild-type cells, suggesting that this protein, while not essential for PSII biogenesis or function, plays a role in the optimization of PSII activity.

Amino Acid Sequence↗
PubMed1995

Specific degradation of the D1 protein of photosystem II by treatment with hydrogen peroxide in darkness: implications for the mechanism of degradation of the D1 protein under illumination.

The D1 protein of the photosystem II (PSII) reaction center has a rapid turnover and is specifically degraded under illumination in vivo. When isolated PSII membranes were treated in darkness with 10 mM hydrogen peroxide (H2O2), an active form of oxygen that is generated at the acceptor side of PSII under illumination, proteins of the PSII reaction center were specifically damaged in almost the same way as observed under illumination with strong light. The D1 protein and, to a lesser extent, the D2 protein were degraded to specific fragments, and cross-linked products (the covalently linked adduct of the D1 protein and the alpha subunit of cytochrome b559 and the heterodimer of the D1 and D2 proteins) were generated concomitantly. The site of cleavage of the D1 protein that gave rise to a major fragment of 22 kDa was located in the loop that connects membrane-spanning helixes IV and V. Treatment with H2O2 caused the same damage to proteins in isolated thylakoids and in core complexes that contained the non-heme iron at the acceptor side, but not in isolated reaction centers depleted of the iron. From these observations and the effects of reagents that are known to interact with the non-heme iron, it is suggested that the damage to proteins is caused by oxygen radicals generated by the non-heme iron in the Fe(II) state in a reaction with H2O2. It is proposed, moreover, that a similar mechanism is operative during the selective and specific degradation of the D1 protein under illumination.

Chloroplasts↗
PubMed1995

Synthesis and enantioselectivity of optically active 1- and 3-substituted 4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols and related compounds as norepinephrine potentiators.

Optically active 1,2-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (1R,4R-3a and 1S,4S-3b, 1S,4R-4a, and 1R,4S-4b) and 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolines (4S-5a and 4R-5b) were prepared in order to examine the effects of the 1-, 3-, and 4-substituents of 2-methyl-4-phenyl- 1,2,3,4-tetrahydroisoquinolin-4-ol (PI-OH) (1) on the enantioselectivity for norepinephrine (NE) potentiating activity. The conformations and absolute configurations of 3-5 were determined from their 1H-NMR and circular dichroism (CD) spectra and by single-crystal X-ray diffractometric analysis. The NE potentiating activity of the optically active 3-5 and previously prepared 3-methyl derivatives (3R,4R-6a and 3S,4S-6b) of PI-OH were tested. The results show that compounds 3, 4, and 6 had high enantioselectivity for NE potentiation: the 4R series of the enantiomers exhibited activity but not the 4S-enantiomers. The activity of the 4-desoxy compound 5 also resided exclusively in the 4S-enantiomer. These findings suggest the presence of a specific receptor for NE uptake, and the enantiomers 3a, 4a, 5a, and 6a may be antagonistic at this NE uptake receptor.

Adrenergic Uptake Inhibitors↗
PubMed1995

Synthesis and biological evaluation of 3,4-diphenyl-1,2-dihydroisoquinolines as a new tamoxifen analogue.

3,4-Diphenyl-1,2-dihydroisoquinoline derivatives (1) as a new tamoxifen analogue were synthesized with trifluoromethanesulfonic acid from 3,4-diphenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (2), which were prepared by intramolecular Barbier reaction of N-(2-iodobenzyl)phenacylamines. Anti-proliferative activities of 1 and 2, and 3,4-diphenyl-1,2,3,4-tetrahydroisoquinolines (3) prepared by NaBH4 reduction of 1 against human mammary carcinoma MCF-7 cell line and human nasopharyngeal carcinoma KB cell line were evaluated. 1,2-Dihydroisoquinoline (1a) was the most active against MCF-7 cells in the compounds tested and the activity [IC50(micrograms/mL) 0.94] was nearly equipotent to that of tamoxifen. The structure-activity relationships of the compounds 1,2 and 3 were discussed.

Antineoplastic Agents↗
PubMed1994

Chemical crosslinking studies of extrinsic proteins in cyanobacterial photosystem II.

Chemical crosslinking with a zero-length crosslinker, 1-ethyl-3-(3-dimethylaminopropyl) carbodimide hydrochloride, was applied to a cyanobacterial photosystem II complex retaining three extrinsic proteins, the 33 kDa manganese-stabilizing protein, cytochrome (cyt) c-550 and the 12 kDa protein. Three major crosslinked products were obtained in addition to the crosslinked product between the extrinsic 33 kDa and the intrinsic CP47 proteins. They were identified to be: cyt c-550-12 kDa; cyt c-550-12 kDa-33 kDa; D2-cyt c-550-12 kDa. These results indicate that the three extrinsic proteins are closely located with each other in cyanobacterial PSII, supporting the previous proposal that, like the 33 kDa protein; cyt c-550 and the 12 kDa protein are associated with PSII at the lumenal side of thylakoids. The results also suggested that the D2 reaction center protein provides a direct binding site for the extrinsic cyt c-550.

Binding Sites↗
PubMed1994

Synthesis and pharmacological evaluation of phenolic 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols as a new norepinephrine potentiator.

2-Methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline-4-ol(PI-OH) (2a) and its derivatives form a new class of compounds possessing norepinephrine (NE) potentiating activity. As a new series of compounds, the isomeric 4-(4-hydroxyphenyl)- and 4-(3-hydroxyphenyl)-2-methyl-1,2,3,4- tetrahydroisoquinolin-4-ols (3a and 3b), and 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinolin-4-ol (3c) were prepared and their NE potentiating activities were evaluated. The 4-(4-hydroxyphenyl) analogue (3a) had only moderate activity and the 4-(3-hydroxyphenyl) analogue (3b) possessed a slightly higher activity than PI-OH. The 4-(3,4-dihydroxyphenyl) analogue (3c) was the most active compound and the pD2 value was 7.71 +/- 0.06 (activity ratio; 26.9 fold) at a concentration of 3 x 10(-6) M. These results indicate the importance of dihydroxyphenylethanolamine moiety of 3c for the inhibition of NE uptake.

Animals↗
PubMed1994

[Two siblings with congenital adrenocortical unresponsiveness to ACTH showing peripheral neuropathy--morphometric evaluation of the sural nerve].

A 13-year-old boy, with the diagnosis of congenital adrenocortical unresponsiveness to ACTH (ACTH insensitivity) at age 7, developed a steppage gait, when under glucocorticoid replacement therapy at age 13. The parents were healthy and not consanguinous. On general physical examination, a mild diffuse skin hyperpigmentation was noted. Neurological examinations revealed that all the muscle stretch reflexes of both limbs were absent without pathologic reflexes. Pes cavus was found bilaterally. A slight decrease of tactile sensation was noted distal to the ankle joints. Pain sensation was slightly decreased in the toes. On laboratory examination, the conduction velocities of the left ulnar and median motor nerves were 51 and 45 m/sec, respectively, which are normal. No M-wave responses were obtained by electrical stimulation of the tibial and peroneal nerves. The coefficient of the variation of the R-R interval from ECG recordings was normal. Orthostatic hypotension was not observed. Achalasia was negative on the barium swallow esophagram. Therefore, it was concluded that he had motor and sensory polyneuropathy, and a right sural nerve biopsy was performed. A 12-year-old girl, a sister of the boy described above, with the diagnosis of ACTH insensitivity at age 5, noted a pain on the medial aspect of the left sole after skating. On general physical examination, a mild diffuse skin hyperpigmentation was discovered. On neurological examination, a spontaneous pain with dysesthesia was noted on the plantar aspect of the 1st, 2nd and 3rd left toes and on the anterior and medial aspect of the sole. Otherwise she was normal. A diagnosis of the left tarsal tunnel syndrome was made.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[The actual conditions of patients with intractable diseases in Hiroshima Prefecture].

All 3,515 patients of intractable diseases who received medical benefits in Hiroshima prefecture were surveyed to determine actual conditions of daily life while being treated. This is the first study in Japan, which has looked at daily life of all patients of intractable diseases at the level of a whole prefecture. Effective collection rate of the questionnaire was 78.8% (2,768 cases). The results are summarized as follows: 1) Many patients and their families wish to be treated at home, with the more severely impaired patients expressing a greater need for home care. 2) Large regional differences were seen in required travel time to visit the hospital, and in the percentage of patients and their families who expressed a desire for medical specialists in intractable diseases for their region. 3) While income of families of the severely impaired patient was generally low, their medical payment burden was heavy. In addition families of patients were heavily burdened physically and mentally. The tasks that lie ahead in the care of patients of intractable diseases would be home care assistance, correction of regional differences, and financial aid for severely impaired patients.

Activities of Daily Living↗
PubMed1992

Synergism in insulin-like effects of molybdate plus H2O2 or tungstate plus H2O2 on glucose transport by isolated rat adipocytes.

The effect of molybdate, tungstate, molybdate plus H2O2 or tungstate plus H2O2 on 3-O-methylglucose (3-O-MG) uptake was studied in isolated rat adipocytes to investigate whether these agents possess an insulin-like action. High concentrations (10-30 mM) of molybdate or tungstate significantly stimulated the uptake of 3-O-MG while 1 mM of the metaloxides did not. The combination of 1 mM molybdate and 1 mM H2O2, or 1 mM tungstate and 1 mM H2O2 induced striking stimulation of the uptake of 3-O-MG in a synergistic manner, whereas 1 mM H2O2 alone showed only a small effect. The effect of metaloxides plus H2O2 (1 mM) and the effect of insulin (20 nM) were not additive, and both effects were ATP or energy dependent based on experiments using KCN. These results indicate that a weak insulin-like effect of molybdate or tungstate is potentiated synergistically with H2O2, presumably by producing peroxocompounds. Based on the present findings, these new agents may be useful for investigating the mechanism of insulin action and may indicate a new class of drugs for diabetes mellitus.

3-O-Methylglucose↗
PubMed1992

Purification and characterization of the photosystem I complex from the filamentous cyanobacterium Anabaena variabilis ATCC 29413.

A photoactive photosystem I complex has been purified from the filamentous, nitrogen-fixing cyanobacterium Anabaena variabilis ATCC 29413. Cells were broken using glass beads, and the membrane fraction was solubilized with beta-dodecyl maltoside followed by two rounds of fast protein liquid chromatography on anion exchange columns. The polypeptide composition of the isolated complex was determined by sodium dodecyl sulfate-urea-polyacrylamide gel electrophoresis and N-terminal amino acid sequencing of the fractionated proteins. The purified complex consists of at least 11 proteins, identified as the PsaA, PsaB, PsaC, PsaD, PsaE, PsaF, PsaI, PsaJ, PsaK, PsaL, and PsaN proteins. The spectrum of the flash-induced absorbance change measured between 670 and 830 nm shows that the purified complex contains 99 +/- 11 chlorophyll a molecules per P700, the primary donor in photosystem I. The kinetics of the rereduction of oxidized P700 following an actinic flash indicate that forward electron transfer from P700 to the FA/FB iron-sulfur center acceptors is functional in the isolated complex.

Amino Acid Sequence↗
PubMed1992

Stoichiometric association of extrinsic cytochrome c550 and 12 kDa protein with a highly purified oxygen-evolving photosystem II core complex from Synechococcus vulcanus.

A highly purified, native photosystem II (PS II) core complex was isolated from thylakoids of Synechococcus vulcanus, a thermophilic cyanobacterium by lauryldimethylamine N-oxide (LDAO) and dodecyl beta-D-maltoside solubilization. This native PS II core complex contained, in addition to the proteins that have been well characterized in the core complex previously purified by LDAO and Triton X-100, two more extrinsic proteins with apparent molecular weights of 17 and 12 kDa. These two proteins were associated with the core complex in stoichiometric amounts and could be released by treatment with 1 M CaCl2 or 1 M alkaline Tris but not by 2 M NaCl or low-glycerol treatment, indicating that they are the real components of PS II of this cyanobacterium. N-Terminal sequencing revealed that the 17 and 12 kDa proteins correspond to the apoprotein of cytochrome c550, a low potential c-type cytochrome, and the 9 kDa extrinsic protein previously found in a partially purified PS II preparation from Phormidium laminosum, respectively. In spite of retention of these two extrinsic proteins, no homologues of higher plant 23 and 17 kDa extrinsic proteins could be detected in this cyanobacterial PS II core complex.

Amino Acid Sequence↗
PubMed1992

In vivo and in vitro effects of cyclosporin A on glucose transport by soleus muscles of mice.

The effect of cyclosporin A (CyA) on 2-deoxyglucose (2DG) uptake by soleus muscles of ICR mice was studied in vivo and in vitro. The basal and insulin-stimulated uptakes of 2DG by the muscles as well as the plasma insulin level were significantly decreased by the in vivo treatment of mice with 20 mg/kg/day of CyA for 6 weeks (P less than 0.01 and P less than 0.05), whereas the insulin binding was increased inversely in the muscles from 20 mg/kg/day CyA-treated mice. The insulin-stimulated uptake of 2DG by the muscles was significantly decreased by the in vitro treatment of the muscles with 1, 10 and 100 micrograms/mL of CyA (P less than 0.05 and P less than 0.01, respectively), while the basal uptake of 2DG was not changed by the in vitro treatment of the muscles with CyA. The insulin binding to the muscles was not altered by the in vitro treatment of the muscles with CyA. These findings suggest that CyA affects not only the insulin secretion from the pancreatic islets but also the postbinding mechanisms of insulin action on the glucose transport by the muscles, which may account for a part of the diabetogenic effect of CyA.

Adenosine Triphosphate↗
PubMed1992

Presence of an N-terminal presequence in the PsaI protein of the photosystem I complex in the filamentous cyanobacterium Anabaena variabilis ATCC 29413.

The psaI gene encoding the 5.2 kDa protein component (PsaI) of the photosystem I complex was cloned from the cyanobacterium Anabaena 29413. The gene is present in single copy in this cyanobacterial genome. The nucleotide sequence of a 500 bp region of the cloned DNA revealed the presence of an open reading frame encoding a 46 amino acid long polypeptide. The N-terminal 11 residues are absent in the mature polypeptide and thus represents the first identified cleavable presequence on the PsaI protein. We suggest that this presequence directs the N-terminus of the protein to the thylakoid lumen.

Amino Acid Sequence↗
PubMed1992

An immunopotentiator of beta-1,6;1,3 D-glucan prevents diabetes and insulitis in BB rats.

The preventive effect of an immunopotentiator, beta-1,6;1,3 D-glucan, on the development of diabetes and insulitis was studied in BB rats. The intravenous administration of 1 mg kg-1 week-1 of beta-1,6;1,3 D-glucan from the age of 4 weeks decreased the cumulative incidence of diabetes from 43.3% (13/30) to 6.7% (2/30) (P less than 0.005) and also the incidence of insulitis from 82.4% (14/17) to 26.3% (5/19) at the age of 20 weeks (P less than 0.002). Eight of nine rats were free from diabetes for 5 weeks after stopping beta-1,6;1,3 D-glucan at the age of 20 weeks. The total numbers of leukocytes in the peripheral blood and spleen of the rats were increased by beta-1,6;1,3 D-glucan treatment (P less than 0.05), whereas their T lymphocytes subsets were not changed. These data indicate that immunopotentiators could modulate the autoimmune mechanisms directed to pancreatic islets and inhibit the development of diabetes in BB rats.

Adjuvants, Immunologic↗
PubMed1992

Urinary excretion of human growth hormone in children with short stature: correlation with pituitary secretion of human growth hormone.

Thirty-five children with short-stature underwent insulin-loading and sleep tests for assessment of secretion of human growth hormone. Correlations between the levels of human growth hormone in the serum and urine during the tests were examined to elucidate the clinical significance of urinary human growth hormone levels in short children. The concentration and total amount of human growth hormone in the urine correlated significantly with the peak concentration of serum human growth hormone (r = 0.81, p less than 0.001 and r = 0.80, p less than 0.001, respectively) and the integrated concentration of human growth hormone (r = 0.85, p less than 0.001 and r = 0.85, p less than 0.001, respectively) in the insulin-loading test. The concentration and total amount of human growth hormone in the morning urine also correlated significantly with the peak concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.70, p less than 0.001, respectively) and the integrated concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.72, p less than 0.001, respectively) in the sleep test. The concentration or total amount of human growth hormone in the urine differed significantly among children with human growth hormone deficiency, those with nonendocrine short stature, and those with normal stature (p less than 0.05). These data suggest that measurement of human growth hormone in the urine may be used to assess secretion of human growth hormone, serving as a screening test for human growth hormone deficiency in children.

Adolescent↗
PubMed1992

[Clinical significance of serum CA130 level in women with spontaneous abortion, hydatidiform mole and early normal and tubal pregnancy].

We examined the serum CA130 level in women in early pregnancy with normal (n = 13), and abnormal (n = 28) course. The abnormal course consisted of intrauterine spontaneous abortion (n = 10), hydatidiform mole (n = 3) and tubal pregnancy (n = 15). The serum CA130 level was higher than for normal nonpregnant women (35u/ml) in 69% (9/13) of women with normal pregnancy, 90% (9/10) of those with intrauterine spontaneous abortion and 100% (3/3) of those with hydatidiform mole; the mean value and standard deviation for these three groups were 131 +/- 150u/ml (n = 13), 197 +/- 253u/ml (n = 10), and 47 +/- 15u/ml (n = 3), respectively. In contrast, the serum CA130 level of the 15 women with tubal pregnancy was 28 +/- 21u/ml. Among these patients, all of the 13 women without genital bleeding had a CA130 level within the normal range for nonpregnant women (mean +/- SD; 20 +/- 6u/ml). Since CA130 is abundant in the decidual tissue but is scant in tubal tissue, a high CA130 level in maternal sera during early pregnancy may indicate the presence of the destruction of decidual tissue, while a low or normal CA130 level throughout early pregnancy is regarded as characteristic of tubal pregnancy.

Abortion, Spontaneous↗