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H Maruta

Publications and source records attributed to H Maruta.

At least 73 records · Page 4Linked to original sources
PubMed1992

Asparagine 26, glutamic acid 31, valine 45, and tyrosine 64 of Ras proteins are required for their oncogenicity.

Ras and Rap1 proteins are related GTP-dependent signal transducers which require Gly-12, the effector domain (residues 32-40), and Ala-59 for stimulation of their GTPase activities by GAP1 and GAP3, respectively. The replacement of Gly-12 by Val or Ala-59 by Thr potentiates the Ras oncogenicity and Rap1A antioncogenicity. However, the mutations in the effector domain, in particular the replacement of Thr-35 by Ala, abolish both Ras oncogenicity and Rap1A antioncogenicity, indicating that the effector domain is involved in interactions of these signal transducers with their targets as well as the GAPs. In this paper, we demonstrate that (i) replacement of Tyr-64 of the Ha-Ras protein or Phe-64 of the Rap1A protein by Glu or other non-hydrophobic amino acids reduces their intrinsic GTPase activities and abolishes their stimulation by GAP1 or GAP3, respectively, (ii) replacement of Tyr-64 by Gly and other non-hydrophobic amino acids results in complete loss of the oncogenicity of the v-Ha-Ras protein, indicating that the hydrophobic residue 64, in addition to the known effector domain, is essential for the Ras protein to interact with its target as well as GAP1. In addition we have found that Asn-26, Glu-31, and Val-45 of the v-Ha-Ras protein are required for its oncogenicity. Replacement of the Ras residues at either positions 26, 31, or 45 by the corresponding Rap1A residues abolishes the Ras oncogenicity.

3T3 Cells↗
PubMed1992

The role of Gln61 and Glu63 of Ras GTPases in their activation by NF1 and Ras GAP.

Two distinct GAPs of 120 and 235 kDa called GAP1 and NF1 serve as attenuators of Ras, a member of GTP-dependent signal transducers, by stimulating its intrinsic guanosine triphosphatase (GTPase) activity. The GAP1 (also called Ras GAP) is highly specific for Ras and does not stimulate the intrinsic GTPase activity of Rap1 or Rho. Using GAP1C, the C-terminal GTPase activating domain (residues 720-1044) of bovine GAP1, we have shown previously that the GAP1 specificity is determined by the Ras domain (residues 61-65) where Gln61 plays the primary role. The corresponding domain (residues 1175-1531) of human NF1 (called NF1C), which shares only 26% sequence identity with the GAP1C, also activates Ras GTPases. In this article, we demonstrate that the NF1C, like the GAP1C, is highly specific for Ras and does not activate either Rap1 or Rho GTPases. Furthermore, using a series of chimeric Ras/Rap1 and mutated Ras GTPases, we show that Gln at position 61 of the GTPases primarily determines that NF1C as well as GAP1C activates Ras GTPases, but not Rap1 GTPases, and Glu at position 63 of the GTPases is required for maximizing the sensitivity of Ras GTPases to both NF1C and GAP1C. Interestingly, replacement of Glu63 of c-HaRas by Lys reduces its intrinsic GTPase activity and abolishes the GTPase activation by both NF1C and GAP1C. Thus, the potentiation of oncogenicity by Lys63 mutation of c-HaRas appears primarily to be due to the loss of its sensitivity to the two major Ras signal attenuators (NF1 and GAP1).

Amino Acid Sequence↗
PubMed1992

Characterization of bovine heparin-binding neurotrophic factor (HBNF): assignment of disulfide bonds.

The topology of the disulfides in native heparin-binding neurotrophic factor (HBNF) isolated from bovine brain was studied by proteolytic digestion using trypsin, Asp-N endoproteinase and chymotrypsin and peptide mapping. Disulfide-linked peptides were identified by automated Edman degradation. It has been shown that there are disulfide bonds between Cys15-Cys44, Cys23-Cys53, Cys30-Cys57, Cys67-Cys99 and Cys77-Cys109.

Amino Acid Sequence↗
PubMed1991

[Study of the predictive factors of postoperative blood pressure in cases with primary aldosteronism].

Some patients develop hypertension after adrenalectomy for primary aldosteronism. We treated 60 cases with primary aldosteronism, and the percentages of cases manifesting hypertensive blood pressures after operation were as follows: 40.0% at the first month, 24.2% at the second year, 30.4% at the 5th year after operation. What are the most important clinical factors relating to postoperative blood pressure? Knowledge of those factors would help in predicting the postoperative blood pressure in cases with primary aldosteronism. The relationships between the postoperative blood pressure and several clinical factors were evaluated for a certain postoperative period using multiple regression analyses. The results were as follows: 1. The duration of preoperative hypertension is the major determinant at the second month after operation. 2. The histological findings for the kidney are the major determinant at the 6th month and the first year after operation. 3. At the second year postoperation, the histological findings for the kidney and the familial history of hypertension are the major determinant respectively. 4. The familial history of hypertension is the most determinant at the 5th year after operation. It is concluded that the preoperative duration of hypertension and the histological findings for the kidney are helpful in predicting blood pressure during the first 2 years after operation, while the familial history of hypertension influences the postoperative blood pressure thereafter.

Adrenalectomy↗
PubMed1991

Rsr1 and Rap1 GTPases are activated by the same GTPase-activating protein and require threonine 65 for their activation.

The Rsr1 protein of Saccharomyces cerevisiae has been shown to be essential for bud site selection (Bender, A., and Pringle, J. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 9976-9980). This protein of 272 amino acids shares approximately 50% sequence identity with both Ras and Rap GTPases. However, neither GTP binding nor GTPase activity of the Rsr1 protein has been reported. The Rsr1 protein shares with human Rap1 GTPases the four specific motifs, i.e. Gly-12, residues 32-40, Ala-59, and residues 64-70, that are required for GAP3-dependent activation of the Rap1 GTPases. In this paper we demonstrate that the intrinsic GTPase activity of the Rsr1 protein is stimulated by GAP3 purified from bovine brain cytosol. The Rsr1 GTPase is not activated by either GAP1 or GAP2 which are specific for the Ras and Rho GTPases, respectively. Thus, it appears that the Rsr1 GTPase is a new member of the Rap1 GTPase family. Replacement of Gly-12 by Val in the Rsr1 GTPase completely abolishes the GAP3-dependent activation. The chimeric GTPases, Ras(1-60)/Rsr1(61-168) and Rsr1(1-65)/Ras(66-189), are activated by GAP3 but not by GAP1. Replacement of Thr-65 by Ser in the latter chimeric GTPase completely abolishes the GAP3-dependent activation, indicating that Thr-65 is required for distinguishing GAP3 from GAP1. We have previously shown that Gln-61 and Ser-65 are sufficient to determine the GAP1 specificity. Replacement of Thr-35 by Ala in the common effector domain (residues 32-40) of the chimeric Ras/Rsr1 GTPases completely abolishes GAP3-dependent activation.

Amino Acid Sequence↗
PubMed1991

[Dopaminergic control of gonadotropin secretion in male senescence].

To verify the role of the dopaminergic mechanism in the control of gonadotropin secretion and aging of this mechanism in men, we studied serum gonadotropin response to LH-RH (100 micrograms i.v.) in basal condition and during dopamine infusion (DA 4 micrograms/kg/min). Seven young males (24-29yr.) and twenty aged males (50-80yr.) without endocrinological diseases were included in the present study. Aged male subjects were divided into hyperresponders, in whom maximal LH response to LH-RH without DA infusion exceeded 153.5mIU/ml (mean + 2SD of young male subjects), and non-hyperresponders, in whom maximal LH responses to LH-RH without DA infusion were less than 153.5mIU/ml. In hyperresponders, serum LH response at 30 minutes after LH-RH administration was significantly (p less than 0.05) suppressed by DA infusion. In non-hyperresponders and young male subjects, however, serum LH response to LH-RH was not affected by DA infusion. Basal levels of serum LH and FSH in hyperresponders tended to be higher than that of non-hyperresponders. Total serum testosterone, free testosterone and estradiol levels of hyper and non-hyperresponders failed to reveal any significant differences. These observations suggest that 1) DA directly suppresses gonadotroph responsiveness to LH-RH, 2) in aging men, inhibitory tone imposed on gonadotrophs by DA is decreased, and 3) this decline of DA system can cause hypergonadotropism in aging men, independent of serum sex steroids levels.

Adult↗
PubMed1991

The residues of Ras and Rap proteins that determine their GAP specificities.

The oncogenic transformation of a normal fibroblast by mutated Ras genes can be reversed by overexpression of a Ras-related gene called Rap1A (or Krev1). Both Ras and Rap1A proteins are G proteins and appear to serve as signal transducers only in the GTP-bound form. Therefore, GAP1 and GAP3, which stimulate the intrinsic GTPase activities of normal Ras and Rap1A proteins, respectively, serve as attenuators of their signal transducing activities. In this paper, we describe the enzymatic properties of several mutated Rap1A and chimeric Ras/Rap1A (or -1B) proteins which lead to the following conclusions: (i) the GAP3-dependent activation of both Rap1A and -1B GTPases requires Gly12, but neither Thr61 nor Gln63; (ii) residues 64 to 70 of the Rap1 GTPases are sufficient to determine their specificities for GAP3; and (iii) residues 61 to 65 of the Ras GTPases are sufficient for determining their specificities for GAP1. Thus, the domains of the Ras or Rap1 proteins that determine whether their signals are attenuated by GAP1 or GAP3 are distinct from the N-terminal domain (residues 21 to 54) that determines whether their signals are oncogenic or antioncogenic. The Arg12 mutant of chimeric HaRas(1-54)/Rap1A(55-184) protein has been previously reported to be oncogenic (Zhang, K., Noda, M., Vass, W. C., Papageorge, A.G., and Lowy, D.R. (1990) Science 249, 162-165). In this paper, we show that the Val12 mutant of chimeric HaRas(1-54)/Rap1B(55-184) protein is also oncogenic, suggesting that the C-terminal geranylgeranylation of the Rap 1B protein can replace functionally the C-terminal farnesylation of the Ras protein to allow the G protein to be oncogenic.

Amino Acid Sequence↗
PubMed1991

Characterization of two forms of poly(ADP-ribose) glycohydrolase in guinea pig liver.

A poly(ADP-ribose) glycohydrolase from guinea pig liver cytoplasm has been purified approximately 45,000-fold to apparent homogeneity. The cytoplasmic poly(ADP-ribose) glycohydrolase designated form II differed in several respects from the nuclear poly(ADP-ribose) glycohydrolase I (Mr = 75,500) previously purified from the same tissue (Tanuma et al., 1986a). The purified glycohydrolase II consists of a single polypeptide with Mr of 59,500 estimated by a sodium dodecyl sulfate-polyacrylamide gel. A native Mr of 57,000 was determined by gel permeation. Peptide analysis of partial proteolytic degradation of glycohydrolases II and I with Staphylococcus aureus V8 protease revealed that the two enzymes were structurally different. Amino acid analysis showed that glycohydrolase II had a relatively low proportion of basic amino acid residues as compared with glycohydrolase I. Glycohydrolase II and I were acidic proteins with isoelectric points of 6.2 and 6.6, respectively. The optimum pH for glycohydrolases II and I were around 7.4 and 7.0, respectively. The Km value for (ADP-ribose)n (average chain length n = 15) and the Vmax for glycohydrolase II were 4.8 microM and 18 mumol of ADP-ribose released from (ADP-ribose)n.min-1.(mg of protein)-1, respectively. The Km was about 2.5 times higher, and Vmax 2 times lower, than those observed with glycohydrolase I. Unlike glycohydrolase I, glycohydrolase II was inhibited by monovalent salts. ADP-ribose and cAMP inhibited glycohydrolase II more strongly than glycohydrolase I. These results suggest that eukaryotic cells contain two distinct forms of poly(ADP-ribose) glycohydrolase exhibiting differences in properties and subcellular localization.

Amino Acids↗
PubMed1991

The assessment of bioavailable androgen levels from the serum free testosterone level.

Recently, it has been concluded that measurement of the serum free testosterone level is crucial for evaluating male gonadal function. However, the extent of the decline of serum free testosterone levels with aging and the actual levels in male infertility have not yet been clearly defined. In this study, the clinical significance of serum free testosterone levels was evaluated in a total of 248 subjects, including 120 healthy adult males (54 males aged 20-39, 26 males aged 40-59 and 41 males aged more than 60), 94 infertile males, 28 male hemodialysis patients, and 6 patients with Klinefelter's syndrome. Since the serum free testosterone levels correlate significantly with serum LH and FSH levels among 120 normal adult males, it appears that free testosterone has a biological action on the organ. In the subjects aged over 60, serum free testosterone levels were significantly decreased compared with the decrease of serum total testosterone. Thus, biologically active androgen levels decreased with aging. Serum free testosterone levels tended to decrease significantly from 40 years onwards. In infertile males, serum total testosterone levels were equal to those in normal adult males, but their serum free testosterone levels were significantly lower. This decrease of serum free testosterone may be one of the causes of their hypospermatogenesis. In male hemodialysis patients, serum total and free testosterone levels were not lower than in normal adult males. It is considered that the decline of percentage of serum free testosterone levels in aged males and infertile males was caused by increased serum sex hormone binding globulin (SHBG) levels. Several workers have shown that the production of SHBG is regulated by sex steroid hormones. In this study, however, serum SHBG levels were not correlated with the E2/T ratio. We concluded that measurement of the serum free testosterone level is of value in the endocrinological evaluation of male gonadal function.

Adult↗
PubMed1991

Placental transfer and effects of famotidine on neonates.

The effect of famotidine on neonates was studied in 34 obstetric patients who underwent elective cesarean section. In the famotidine group, 20 mg of famotidine was intramuscularly injected at 60 min before induction of anesthesia, and 0.5 mg of atropine was injected at 30 min before induction. In the control group, only atropine was given. Ratio of famotidine concentration in the umbilical venous blood to that in the maternal venous blood was determined as 0.64 +/- 0.13 (mean +/- SD). No significant differences were noted in the Apgar scores, neonatal gastric acidity, and results of liver function tests between the two groups. No side effect, such as the development of gastrointestinal infections, was observed.

Journal Article↗
PubMed1991

[Therapeutic efficacy of testolactone (aromatase inhibitor) to oligozoospermia with high estradiol/testosterone ratio].

To our knowledge, the action of estradiol which is produced from testosterone by aromatase on human spermatogenesis has not been fully clarified. In oligozoospermia, with high values of E2/T ratio, it is considered that the role of estradiol is suppressive to spermatogenesis. In this study, alteration of spermatogenesis was evaluated when serum estradiol levels were decreased by suppression of aromatase activity. Nine male infertile patients were treated with testolactone (Teslac: 1.0 g/day, for 3 months), one of the aromatase inhibitors. Four of them had an increase in sperm count (more than 10 x 10(6)/ml relative to base line). In endocrinological findings, serum estradiol levels and E2/free T ratio were significantly decreased after treatment. Serum free testosterone levels were significantly increased in all cases, presumably from decreased sex hormone binding globulin (SHBG) levels. These findings suggested the effectiveness of the administrated aromatase inhibitor. In particular four patients whose sperm counts were improved after testolactone treatment had high values of basal serum estradiol levels and E2/free T ratio before treatment, and these values were normalized after treatment. In conclusion we suggest that an aromatase inhibitor may be effective to male infertile patients with high serum estradiol levels.

Adult↗
PubMed1991

Effects of chemically defined tannins on poly (ADP-ribose) glycohydrolase activity.

Three classes of chemically defined tannins, gallotannins, ellagitannins and condensed tannins were examined for their inhibitory activities against purified poly (ADP-ribose) glycohydrolase. Ellagitannins showed higher inhibitory activities than gallotannins. In contrast, condensed tannins, which consist of an epicathechin gallate (ECG) oligomer without a glucose core were not appreciably inhibitory. Kinetic analysis revealed that the inhibition of ellagitannins was competitive with respect to the substrate poly(ADP-ribose), whereas gallotannins exhibited mixed-type inhibition. These results suggest that conjugation with glucose of hexahydroxy-diphenoyl (HHDP) group, which is a unique component of ellagitannins, potentiated the inhibitory activity, and that the structure of ellagitannins may have a functional domain which competes with poly(ADP-ribose) on the poly(ADP-ribose) glycohydrolase molecule.

Glycoside Hydrolases↗
PubMed1991

[Clinical application of Modulith SL20 on extracorporeal shock wave lithotripsy for upper urinary tract calculi].

Thirty-nine patients, 27 males and 12 females with renal and ureteral stones, were treated using the Modulith SL 20 between October 1990 and January 1991. Thirty-three of the 39 cases had a single session of extracorporeal shockwave lithotripsy (ESWL) and the other six cases had two sessions. The pulverization rate of ESWL by this device was 84.6%. According to the X-rays taken 21 days after ESWL, of the 37 cases, 14 (37.8%) were stone-free, 18 (48.7%) had residual sandy stones less than 4 mm in diameter, five (13.5%) had residual stone fragments larger than 4.1 mm in diameter, and two cases were not clear. Using the criterion of cases which can be expected to have spontaneous passage, in other words, residual stones less than 4 mm in diameter, lithotripsy with the Modulith SL 20 was regarded as "effective" in 32 of the 37 cases (86.5%). As side effects of this treatment, hematuria was observed for several days after ESWL in all patients, but not other serious complications were observed. Among the 37 cases in which the grade could be evaluated the evaluation for 24 (64.9%) was "useful" and that for 13 (35.1%) "useful to some extent". Therefore, ESWL was performed very successfully.

Adult↗
PubMed1990

[Determination of the normal range of serum LH and FSH levels in normal adult males--comparison with IRMA and RIA].

To determine the normal range of serum LH and FSH levels, blood samples from 53 normal adult males were measured by a double antibody radioimmunoassay system and a new immunoradiometric assay (IRMA) system. It was necessary to evaluate the individual pulsatile secretion and the differences in measured values among laboratories to determine the normal range. Therefore, in 53 normal adult males lacking any evidence of hormonal abnormalities, blood was sampled at 9:00 a.m. daily for 3 days, and these samples were measured in 3 laboratories. The result of the hormone concentration of blood sample was not appropriate as the normal range because of the high amplitude of LH and FSH pulses. Coefficient values (CV) between the mean value of the first two samples and the mean value of all three samples were small. Therefore, the mean value of the first two samples was clinically accurate for use as the normal range. Significant differences in measured values were observed among the 3 laboratories. The normal range, which included individual pulsatile secretion, and the differences in measured values among the laboratories was as followings: LH (RIA): 7.6-13.7 mIU/ml, LH (IRMA): 2.1-4.7 mIU/ml, FSH (RIA): 4.7-9.5 mIU/ml, FSH (IRMA): 3.0-7.4 mIU/ml. The serum LH and FSH levels of 68 untreated male infertility patients tended to rate high with respect to our normal range. It was considered that the normal range determined in this study was useful for clinical management.

Adult↗
PubMed1990

[Study on new quinolone-resistant strains isolated from urine--annual changes of its frequency and the relation to drug volume].

There is concerned that the new quinolone-resistant strains have increased along with its widespread usage. We analysed the annual changes in frequency of ofloxacin-resistant strains isolated from urine in the past four years at two different types of hospitals, department of urology in Sapporo Medical College and Muroran City Hospital, since the usage of these agents seem to be related to the annual changes of the frequencies. The results were summarised as follows: 1) In the two hospitals, drug volume of the new quinolones had been increased, in particular, the past six years from 1984. 2) The annual changes in frequency of ofloxacin-resistant Staphylococcus aureus have been increasing from 0 to 41.2 percent in Sapporo Medical College and 16.7 to 96.7 percent in Muroran City Hospital. The frequency of ofloxacin-resistant Pseudomonas aeruginosa also have been increasing from 24 to 66.7 percent in Sapporo Medical College and 37.5 to 81.8 percent in Muroran City Hospital. 3) The frequency of ofloxacin-resistant indole positive Proteus spp. and Serratia marcescens for four years at Sapporo Medical College (indole positive Proteus spp.: 0-1.8 percent, Serratia marcescens: 10-43 percent) was very different from that at Muroran City Hospital (indole positive Proteus spp.: 65-82 percent, Serratia marcescens: 71-100 percent). The difference seems to be caused by the hospital acquired infection.

4-Quinolones↗
PubMed1990

[Therapeutic evaluation of male infertility--the increase of seminal transferrin level and the improvement in sperm concentration following administration of clomiphene citrate].

This study was designed to evaluate the functional changes of Sertoli cells following the administration of clomiphene citrate for male infertility. Sperm count and seminal transferrin level were measured before and after the treatment in 22 cases of oligozoospermia (sperm count: less than 20 X 10(6)/ml) and 14 cases of subnormal sperm count group (sperm count: 20-30 X 10(6)/ml). Clomiphene citrate was administered per os for more than 3 months consecutively in a dose of 25 mg/day. Seminal transferrin concentration increased more than 1.5 times compared with pre-treatment level in 6 cases (16.7%). Among these patients, sperm count markedly increased (20 X 10(6)/ml or more than the pre-treatment level) in 3 cases (50%) and slightly increased (10 X 10(6)/ml or more than pre-treatment) in 1 case (16.7%). In 30 cases, in which seminal transferrin level did not increase, sperm count markedly increased in 6 cases (20%) and slightly increased in 6 cases (20%). Thus, sperm count was improved more frequently in the cases in which seminal transferrin level remained elevated than the cases with no elevation of serum transferrin level. Serum FSH level of patients whose seminal transferrin level remained elevated after the treatment was significantly higher than that of patients with no elevation of serum transferrin level (mean +/- SD = 32.8 +/- 18.0 mIU/ml v.s. 14.4 +/- 11.7 mIU/ml, respectively). These data suggested that the activation of Sertoli cells may contribute to the increase of sperm count following the administration of clomiphene citrate and the elevated seminal transferrin secretion may be related to the increase of serum FSH level following this treatment.

Clomiphene↗
PubMed1990

[Studies on incidental carcinoma of the prostate].

We reviewed 157 patients retrospectively with incidental carcinoma of the prostate who had been treated at our collaborating hospitals during the past ten years. Of 5212 patients with benign prostatic hyperplasia who received subcapsular prostatectomy or transurethral resection of the prostate (TUR-P), 157 (3.0%) were diagnosed as having an incidental carcinoma of the prostate, which was somewhat lower than that in previously published reports. Of these, 30 and 127 patients were in stage A1 and A2, respectively. Well, moderately and poorly differentiated carcinomas were found in 44.6%, 36.7% and 18.5% of the patients, respectively. The incidence of poorly differentiated carcinoma in the study seemed to be higher than that in the previous reports. A positive correlation was identified in TUR-P specimens between the carcinoma differentiation and its extension which was evaluated by cancer-positive chip ratio. Atypical adenomatous hyperplasia and intraductal dysplasia were identified in 36.9% and 85.3% of the patients with incidental carcinoma, respectively. These incidences tended to become lower as the carcinoma became less differentiated or more extended. Further studies will be necessary to define the significance of these pathological findings as a direct biological precursor of prostatic carcinoma. Six out of the 157 patients with incidental carcinoma showed a progression during the follow-up period. All of these patients were in stage A2 and all but one showed a histology of moderately or poorly differentiated carcinoma at the time of diagnosis. Radical prostatectomy or radiation therapy as well as endocrine therapy should be considered as treatment modalities for stage A2 patients, when staging lymphadenectomy shows no pelvic lymph node metastasis.

Humans↗