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Biomedical subjects

S Ikegami

Publications and source records attributed to S Ikegami.

At least 37 records · Page 2Linked to original sources
PubMed2000

Growth hormone therapy in achondroplasia.

Achondroplasia is one of the most common causes of severe rhizomelic dwarfism. We have previously reported the growth-promoting effect of growth hormone (GH) in this disorder. In this expanded clinical study, dose dependency and the long-term effect of GH were also investigated. Prepubertal children with achondroplasia (82 males and 63 females) were randomly divided into 2 groups. Patients were treated with 0.5 IU/kg per week or 1.0 IU/kg per week subcutaneous recombinant human GH. Of 75 patients, the mutational analysis of fibroblast growth factor receptor-3 revealed that G1138A was detected in 70 and G1138C was found in 2. GH increased growth rate and height z score in a dose-dependent manner. GH also increased serum insulin-like growth factor (IGF)-I, IGF-binding protein-3 and osteocalcin. No adverse effects were observed in either group. We conclude that GH therapy is a useful method for improvement of severe growth retardation of achondroplasia.

Achondroplasia↗
PubMed2000

[Osteoporosis].

Explore the source record for details and available documents.

Calcitonin↗
PubMed1999

Presence of phospholipid-neutral lipid complex structures in atherosclerotic lesions as detected by a novel monoclonal antibody.

A novel monoclonal antibody (ASH1a/256C) that recognizes atherosclerotic lesions in human and Watanabe heritable hyperlipidemic (WHHL) rabbit aortae is described. When (123)I-labeled ASH1a/256C antibody is injected intravenously into WHHL rabbits, it associates specifically with fatty streaks on the aorta. The antigen recognized by the antibody is lipid, based on extraction with chloroform and methanol from WHHL rabbit tissues. The antigen, purified by high performance liquid chromatography, was shown to be phosphatidylcholine (PC), which contains unsaturated fatty acyl groups based on analyses utilizing (1)H and (13)C nuclear magnetic resonance, Fourier transfer-infrared spectrum, and mass spectrometry. The antibody did not react with other classes of phospholipids or neutral lipids when tested using an enzyme-linked immunosorbent assay. When PC was mixed with either cholesterol, cholesteryl ester, or triacylglycerol, however, the reactivity of the antibody to PC increased up to 8-fold. Homogenates of aorta tissue obtained from normal and WHHL rabbits were fractionated using sucrose density gradient ultracentrifugation in which neutral lipid droplets, cellular membranes, and proteins are separated. The phospholipid content in cellular membrane fractions from WHHL rabbits was twice as high as that of normal rabbits, and there was an enormous difference in the antigenic activity in these fractions. The content of cholesterol in the cellular membrane fraction of WHHL rabbits was approximately 50 times higher than that of normal rabbits. Addition of neutral lipids to the cellular membrane fraction of normal rabbit markedly increased the antigenic activity. Atheromatous lesions in thickened WHHL rabbit aortic intima that were rich in lipid droplets were stained positively with ASH1a/256C immunohistochemically. These results strongly suggest that PC-neutral lipid complex domains are formed in atherosclerotic lesions.

Animals↗
PubMed1999

Increased anxiety and impaired pain response in puromycin-sensitive aminopeptidase gene-deficient mice obtained by a mouse gene-trap method.

A mouse mutation, termed goku, was generated by a gene-trap strategy. goku homozygous mice showed dwarfism, a marked increase in anxiety, and an analgesic effect. Molecular analysis indicated that the mutated gene encodes a puromycin-sensitive aminopeptidase (Psa; EC 3. 4.11.14), whose functions in vivo are unknown. Transcriptional arrest of the Psa gene and a drastic decrease of aminopeptidase activity indicated that the function of Psa is disrupted in homozygous mice. Together with the finding that the Psa gene is strongly expressed in the brain, especially in the striatum and hippocampus, these results suggest that the Psa gene is required for normal growth and the behavior associated with anxiety and pain.

Aminopeptidases↗
PubMed1999

High-Fat diet enhances accumulation of hexachlorobenzene in rat dams and delays its transfer from rat dams to suckling pups through milk.

Effect of diets on the distribution and transfer of hexachlorobenzene (HCB) from dams to fetuses and suckling pups was investigated. In pregnant rats, the amount of HCB accumulated in fat tissues of the high-fat diet group was higher than that of the control diet group (P < 0.05). The amounts of HCB in fetuses of the high-fat and control diet groups were estimated to be about 0.28 and 0.12% of the dam's total intake during pregnancy, respectively. In both groups, a large proportion of HCB in dams disappeared during lactation period and was transferred to their pups through the milk. In the pups of the high-fat diet group, the amount of HCB in stomach contents was lower immediately after birth and decreased slowly compared with that in the control diet group during lactation. These results showed that a high-fat diet reduced the speed of the transfer of HCB from the dams to their suckling pups through milk.

Adipose Tissue↗
PubMed1999

Mild impairment of learning and memory in mice overexpressing the mSim2 gene located on chromosome 16: an animal model of Down's syndrome.

Human Sim2 is a product of one of the genes located on human chromosome 21q22 and is a homolog of Drosophila single-minded ( sim ) which is a critical player in midline development of the central nervous system of the fly. Since Sim2 mRNA is expressed in facial, skull, palate and vertebra primordia in human and rodent embryos, features that are associated with phenotypes of Down's syndrome (DS), its trisomic state is suspected to contribute to the symptoms of DS. Here we describe that mSim2 mRNA is expressed in hippocampus and amygdala of adult mice, and that while mice overexpressing mSim2 under the control of the beta-actin promoter are viable and fertile and have superficially normal skeletal, brain and heart structures, they exhibit a moderate defect in context-dependent fear conditioning and a mild defect in the Morris water maze test. Taken together, our data show that overdosage of Sim2 may be important for the pathogenesis of Down's syndrome, especially mental retardation.

Animals↗
PubMed1999

Selective effects of genistein, a soybean isoflavone, on B-lymphopoiesis and bone loss caused by estrogen deficiency.

Genistein, an isoflavone abundantly present in soybeans, has structural similarity to estrogen, suggesting that genistein may act as a phytoestrogen. To examine the possible role of genistein in hemopoiesis and bone metabolism, female mice were either sham-operated or ovariectomized (OVX), and selected OVX mice were administered genistein for 2-4 weeks (0.1-0.7 mg/day) or 17beta-estradiol (E2; 0.01-0.1 microg/day) s.c., using a miniosmotic pump (Alza Corp., Palo Alto, CA). In OVX mice, uterine weight declined but was completely restored by E2 administration. In contrast, genistein did not demonstrate a reversal of the OVX-induced uterine atrophy. The number of bone marrow cells markedly increased, 2-4 weeks after OVX, and most of these were B220-weakly positive pre-B cells. The increased B-lymphopoiesis was completely restored, not only by E2 but also by genistein administration. In OVX mice, the trabecular bone volume of the femoral distal metaphysis, measured by microcomputed tomography scanning and dual-energy x-ray absorptiometry, was markedly reduced; and genistein restored this, as did E2. These results indicate that genistein exhibits estrogenic action in bone and bone marrow, to regulate B-lymphopoiesis and prevent bone loss, without exhibiting estrogenic action in the uterus. Phytoestrogens may be useful for preventing bone loss caused by estrogen deficiency in females.

Animals↗
PubMed1999

Effects of sodium alginate and fish oil to reduce trichloroethylene accumulation in rats.

This study was conducted to examine the effect of dietary sodium alginate and fish oil on bodily accumulated trichloroethylene (TCE), which has been widely used as a halogenated solvent and is metabolized at a high rate. Each of three groups of rats was fed on either of diets containing cellulose-soybean oil (control), Na-alginate-soybean oil or cellulose-fish oil for 3 wk, and thereafter given a single oral dose of TCE (100 mg (0.76 mmol)/rat). TCE levels in the blood were monitored for 10 h after the administration of TCE. The peak concentrations of TCE in the blood tended to be higher in the alginate and fish oil groups as compared with those in the cellulose-soybean oil group, but not to a significant extent. TCE concentrations in the liver, kidney, brain and the three fat tissues (epididymal, perirenal and subcutaneous) were significantly lower in the alginate and fish oil groups than in the cellulose-soybean oil group. Fat tissue weights were also lower in the alginate group and fish oil group. The hepatic drug metabolizing enzymes could not account for the remarkable decreases of residual TCE contents in the alginate and fish oil groups. These findings indicate that the metabolism and excretion of TCE might be accelerated in animals with reduced fat tissue mass.

Adipose Tissue↗
PubMed1999

[A clinical study of recurrence and progression of grade 3 superficial bladder tumor].

Forty-one patients who had grade 3, superficial, transitional cell carcinoma of the bladder were treated with transurethral resection of bladder tumor between January, 1986 and April, 1998. The clinicopathological studies were conducted on intravesical recurrence, disease progression, and prognosis using multivariate analyses. Intravesical recurrence was found in 18 patients (43.9%), and the recurrence-free rate was 77.0% for 1 year. The 3- and 5-year recurrence-free rates were 57.7% and 38.5% for patients with stage pTa disease, and 36.3% and 36.3% for patients with stawe pT1-disease. There was a significant difference between the recurrence-free rates in the patients with stage pTa disease and those with stage pT1 disease (p < 0.01). Disease progression was observed after a mean period of 14.2 months after treatment in 6 patients (14.6%) with pT1 tumors. Three of these patients died of cancer. In the multivariate analyses with clinical and pathological factors, bladder irritability, urine cytology after initial treatment, and tumor multiplicity were the factors contributing to a high risk for recurrence. Intravesical instillation with Calmette-Guerin bacillus was found to prevent recurrence. These results suggest that radical surgery should be performed in a timely manner in patients with G3-stage pT1 tumors because they have a higher risk of recurrence and progression as compared to patients with G3-stage pTa tumors.

Administration, Intravesical↗
PubMed1998

Inhibition of sea urchin fertilization by jaspisin, a specific inhibitor of matrix metalloendoproteinase.

Jaspisin, originally isolated from a marine sponge as an inhibitor of the hatching of the sea urchin (Hemicentrotus pulcherrimus) embryo, causes inhibition of sea urchin fertilization. Electron microscopic examination revealed that the acrosome reaction was induced in jaspisin-treated sperm when they were incubated with an intact egg. The acrosome-reacted sperm bound to the vitelline layer by the acrosomal material surrounding the acrosomal process. However, fusion of the acrosomal process and the egg plasma membrane failed to take place. Membrane potential changes were monitored using eggs preloaded with a membrane potential-sensitive fluorochrome, di-8-ANEPPS. Depolarization of the membrane potential, normally observed in the fertilized egg was not observed in the egg inseminated in the presence of jaspisin, indicating the absence of electrical continuity between the jaspisin-treated egg and sperm. Jaspisin inhibited the activities of matrix metallo-endoproteinase members but not of other types of proteinases. These results provide strong, albeit indirect, evidence that a matrix metallo-endoproteinase(s) is involved in the process of gamete fusion during sea urchin fertilization.

Acrosome↗
PubMed1998

Sperm-induced local [Ca2+]i rise separated from the Ca2+ wave in sea urchin eggs in the presence of a gamete fusion inhibitor, jaspisin .

An increase in intracellular Ca2+ concentration ([Ca2+]i) at a focal plane was recorded simultaneously with sperm-egg binding and membrane current upon insemination of sea urchin Hemicentrotus pulcherrimus eggs. No change in current and [Ca2+]i occurred in the presence of jaspisin, a novel substance that inhibits metallo-endoproteinase and sperm-egg membrane fusion (S. Ikegami, H. Kobayashi, Y. Myotoishi, S. Ohta and K. H. Kato (1994) J. Biol. Chem. 269, 23262-23267). With low doses of jaspisin, a spermatozoon first produced a step inward current (I(on)) as an indication of gamete membrane fusion and then induced a local [Ca2+]i rise at the site of sperm attachment 6-10 seconds after I(on). The sperm, however, soon detached from the egg. Increasing inward current was abruptly cut off (I(off)) within 9-15 seconds and the local [Ca2+]i rise began to decline 1-3 seconds after I(off). In most cases, no further responses or an elevation of fertilization envelope (FE) occurred. In some cases, [Ca2+]i at the sperm attachment site increased again even after the sperm detached and triggered a Ca2+ wave which caused an activation current and FE formation. This recording of a gamete membrane-fusion-induced local [Ca2+]i rise, separated from the Ca2+ wave, is a key phenomenon for elucidating the initial sperm stimulation of the egg at fertilization.

Animals↗
PubMed1998

Feeding fish oil to rats accelerates the metabolism of hexachlorobenzene.

This study was conducted to examine the influence of dietary fat on the metabolism and excretion of hexachlorobenzene (HCB), a ubiquitous food contaminant which is metabolized at a low rate. Three groups of rats were fed semi-purified diets containing 10 g/100 g of either soybean oil, lard or fish oil for 2 wk and then given a single dose of HCB by intragastric gavage. The concentrations of HCB and pentachlorophenol (PCP), a major metabolite of HCB, were monitored in the blood for 5 d. Fecal excretion of HCB did not differ among the three groups, indicating no difference in HCB retained in the body among the groups. Concentrations of HCB in blood, liver and brain samples from the lard and fish oil groups, the members of which had a low fat tissue mass, were consistently higher as compared with those in samples from the soybean oil group. The concentration of PCP and the PCP/HCB ratio in the blood were higher in the fish oil group than in the other groups. In addition, the amount of PCP excreted in urine was highest in the fish oil group. The hepatic cytochrome P-450 content in the fish oil group was higher than that in the other groups. These findings indicate that feeding fish oil to rats accelerated HCB metabolism. An increase in hepatic HCB concentration due to a small fat tissue mass and high hepatic cytochrome P-450 content may have played a role in accelerating HCB metabolism in the fish oil group.

Adipose Tissue↗
PubMed1998

[A case report of complete inversion of the bladder in an old woman].

A 77-year-old Japanese woman was admitted to our hospital complaining of small urinary volume. Physical examination revealed a light red, edematous, pyriform mass, approximately 7 cm in diameter at the vulva. An orifice posterior to the base of the mass was catheterized and 20 ml of urine was obtained. Roentgenograms of contrast material injection to the orifice demonstrated a space of 20 ml. A diagnosis of complete inversion of the bladder was made. Under epidural anesthesia, attempts were made to reduce the mass through the urethra. The manual reduction proved to be difficult, but was successful by manual compression of the bladder wall and squeezing it back through the urethra, which took approximately 60 minutes. Complete transurethral inversion of the bladder is so rare that not much of the pathogenesis is clarified. In our patient, senility, obesity, multiple labor and surgeries are assumed to have resulted in laxity of the pelvic wall which would be one of the major risk factors for this condition.

Aged↗
PubMed1997

Structure of a covalently cross-linked form of core histones present in the starfish sperm.

The post-translational modification of core histones plays an essential role in chromatin remodeling processes. We recently reported the occurrence of a novel histone modification, involving a epsilon-(gamma-glutamyl)lysine cross-link between a glutamine residue of histone H2B and a lysine residue of histone H4 in the testis of the starfish, Asterina pectinifera[Shimizu, T., Hozumi, K., Horiike, S., Nunomura, K., Ikegami, S., Takao, T., and Shimonishi, Y. (1996) Nature 380, 32]. In order to determine the complete structure of the modified histone heterodimer, p28 from both testis and sperm was purified. p28 was digested with Achromobacter lyticus protease I or Staphylococcus aureus V8 protease to give proteolytic fragments that were separated by HPLC. Amino acid analysis, sequencing, and mass spectrometric analysis of the fragments showed that the amino acid sequences of these fragments are identical to those of both histones H2B and H4, except for two NH2-terminal peptides obtained by digestion with A. lyticus protease I. One of the peptides, K8, was identical to that reported previously, and the other was a here-to-fore unidentified peptide, which was designated K10. Amino acid and positive-ion FAB-MS/MS analyses of K10 showed that it to be a fragment, derived from Gly8-Lys10 of histone H2B and Gly9-Lys16 of histone H4. The yields of K8 and K10 were calculated to be 47 and 42%, respectively, expressed as the percent of the total amount of p28 used in the experiment. Based on these data, the structure of p28 was determined to be a heterodimer, composed of histones H2B and H4, formed through a transglutaminase-catalyzed acyl transfer reaction between Gln9 of histone H2B and Lys5 or Lys12 of histone H4.

Amino Acid Sequence↗
PubMed1997

High-sensitivity mass spectrometry for analysis of posttranslational modifications.

Pulsed fast atom bombardment ionization (pulsed-FAB) mass spectrometry has been developed to improve the sensitivity of tandem mass spectrometry (MS/MS), allowing it to be used for the analysis of very small samples. MS/MS, when used with a magnetic four-sector instrument coupled with the pulsed-FAB system, allows significant enhancement in product ion intensity of over ten-fold in magnitude over conventional FAB. MS/MS was applied to the structural analysis of a unique nuclear protein, designated p28, which was isolated from a histone fraction obtained from starfish testes. The results clearly show that protein p28 is a heterodimer composed of testicular histones H2B and H4 which are cross-linked between Gln9 of H2B and Lys5 of H4.

Amino Acid Sequence↗
PubMed1997

Hexachlorobenzene accumulated by dams during pregnancy is transferred to suckling rats during early lactation.

The distribution of ingested stable, lipophilic environmental pollutants in dams and their transfer to fetuses and sucklings were investigated in rats fed a diet containing a small amount (35.1 nmol/100 g diet) of hexachlorobenzene (HCB). In the first experiment, we examined the distribution of HCB in pregnant and nursing rats fed the HCB diet during pregnancy and lactation. Its transfer to their sucklings was also studied. On d 16 after parturition, HCB concentrations in the blood, and subcutaneous and perirenal fat of nursing rats fed the HCB diet during pregnancy and lactation were approximately 1/3.5, 1/15 and 1/2.8, respectively, those of pregnant rats fed the HCB diet only during pregnancy. On the other hand, the HCB concentrations in the blood, and subcutaneous and perirenal fat of sucklings were approximately 6, 29 and 15 times higher than those of their dams. Therefore, a large amount of HCB apparently was transferred from dams to suckling pups through the milk. In the second experiment, we fed dams the HCB diet only during pregnancy and determined the distribution of HCB in the pregnant rats and fetuses as well as in the nursing rats and suckling pups. The estimated amount of HCB transferred from a dam to her fetuses corresponded to about 0.39% of her total intake during pregnancy. The amount of HCB detected in nursing rats on d 16 after parturition was much smaller than that in the pregnant rats, suggesting that a large proportion of the HCB that accumulated during pregnancy disappeared from the organs and fat tissues during lactation. The HCB concentration in the stomach contents of suckling pups fed by the dams who had consumed HCB before parturition was highest on d 2 after birth and decreased gradually during the 16 d after birth. In the blood, liver and fat tissues of suckling rats, the HCB concentrations increased until 7 d after birth and then decreased gradually. We conclude that the HCB that accumulated in dams during pregnancy was transferred to their suckling pups through milk in the early days after birth.

Animals↗