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Biomedical subjects

A Yamazaki

Publications and source records attributed to A Yamazaki.

At least 55 records · Page 3Linked to original sources

[A case of metachronous lung cancer in which tumor developed within the different ipsilateral lobe over a short period of time and completion pneumonectomy was required].

A 51-year-old man underwent a middle-lower lobectomy for squamous cell carcinoma on February 8, 1996. In July, 1997, a computed tomography revealed a mass shadow in the right upper lung field. Completion pneumonectomy was performed. Histopathological examination showed poorly differentiated adenocarcinoma. This case was the shortest time to occurrence of second tumor in our metachronous lung cancer cases. We must always give attention to exist second primary lung cancer and double primary lung cancer after resection of primary lung cancer.

Adenocarcinoma↗

[A case of superior mediastinal neurinoma resected from the supra-clavicular area].

We report a case of superior mediastinal neurinoma that was resected from the supra-clavicular area. An abnormal shadow on the chest X-ray film was pointed out in a 53-year-old male. A left supra-clavicular mass was subsequently also discovered. We underwent extirpation of the tumor through supra-clavicular approach and confirmed to be a neurinoma histologically. We consider supra-clavicular approach which allows a good view might be useful.

Humans↗

[Application of measuring 99mTc-MAG3 plasma clearance based on one-compartment model (MPC method) to renal transplantation].

Measurement of 99mTc-MAG3 plasma clearance (CLmag) based on one-compartment model (MPC method) was applied to renal transplantation and evaluated for the factors which might affect the calculated results, especially concerning renal depth. Correlation coefficient of CLmag between MPC method using real renal depth and Russell or Bubeck single sampling method was good (r = 0.852 or 0.876, respectively). Regression equation between MPC method and Russell method was y = 1.044x - 3.0 and was more closer to y = x than that between MPC method and Bubeck method. CLmag of MPC method calculated by estimated renal depth from the abdominal thickness was also similar to that by real renal depth. Even if the fixed renal depth, 4 cm, was applied, the coefficient and regression equation between MPC method and Russell method were r = 0.884 and y = 1.004x - 10.2. In conclusion, MPC method is applicable to the evaluation of renal transplants. Though measuring renal depth is best, calculation with fixed renal depth of 4 cm might be practically acceptable.

Adult↗

A possible role of RGS9 in phototransduction. A bridge between the cGMP-phosphodiesterase system and the guanylyl cyclase system.

In the current concept of phototransduction, the concentration of cGMP in retinal rod outer segments is controlled by the balance of two enzyme activities: cGMP phosphodiesterase (PDE) and guanylyl cyclase (GC). However, no protein directly mediates these two enzyme systems. Here we show that RGS9, which is suggested to control PDE activity through regulation of transducin GTPase activity (He, W., Cowan, C. W., and Wensel, T. G. (1998) Neuron 20, 95-102), directly interacts with GC. When proteins in the Triton X-100-insoluble fraction of bovine rod outer segments were isolated by two-dimensional gel electrophoresis and binding of GC to these proteins was examined using a GC-specific antibody, proteins (55 and 32 kDa) were found to interact with GC. However, the activity of GC bound to the 55-kDa protein was not detected. This observation was elucidated by the finding that the 55-kDa protein inhibited GC activity in a dose-dependent manner. Amino acid sequence showed that five peptides derived from the 55-kDa protein were identical to corresponding peptides of RGS9. Together with other biochemical characterization of the 55-kDa protein, these observations indicate that the 55-kDa protein is RGS9 and that RGS9 inhibits GC. RGS9 may serve as a mediator between the PDE and GC systems.

3',5'-Cyclic-GMP Phosphodiesterases↗

Phosphorylation of the gamma subunit of the retinal photoreceptor cGMP phosphodiesterase by the cAMP-dependent protein kinase and its effect on the gamma subunit interaction with other proteins.

Cyclic GMP phosphodiesterase, a key enzyme in phototransduction, is composed of P alpha beta and two P gamma subunits. Interaction of P gamma with P alpha beta or with the alpha subunit (T alpha) of transducin is crucial for the regulation of cGMP phosphodiesterase in retinal photoreceptors. Here we have investigated phosphorylation of P gamma by cAMP-dependent protein kinase and its functional effect on the P gamma interaction with P alpha beta or T alpha in vitro. P gamma, but not P gamma complexed with T alpha (both GTP and GDP forms), is phosphorylated. Measurement of 32P radioactivity in phosphorylated P gamma, analysis of phosphorylated P gamma by laser mass spectrometry, identification of phosphoamino acid, and phosphorylation of mutant forms of P gamma indicate that only threonine 35 in P gamma is phosphorylated. Phosphorylation of P gamma mutants also reveals that the C and N terminals of P gamma which are required for the regulation of P alpha beta functions are not involved in the P gamma phosphorylation but that arginine 33, which is ADP-ribosylated by an endogenous ADP-ribosyltransferase, is required for the phosphorylation. Phosphorylated P gamma has a higher inhibitory activity for trypsin-activated cGMP phosphodiesterase than nonphosphorylated P gamma, indicating that the P gamma-P alpha beta interaction is affected by P gamma phosphorylation. Nonphosphorylated P gamma inhibits both the GTPase activity of T alpha and the binding of a hydrolysis-resistant GTP analogue to T alpha, while P gamma phosphorylation reduces these inhibitory activities. These observations suggest that a P gamma domain containing threonine 35 is involved in the P gamma-T alpha interaction, and P gamma phosphorylation regulates the P gamma-T alpha interaction. Our observation suggests that P gamma phosphorylation by cAMP-dependent protein kinase may function for the regulation of phototransduction in vertebrate rod photoreceptors.

3',5'-Cyclic-GMP Phosphodiesterases↗

Biochemical and pharmacological characterization of FR134043, a novel elastase inhibitor.

FR134043, disodium(Z,1S,15S,8S,24S,27R,29S,34S,37R)-29-ben zyl-21-ethylidene-27-hydroxy-15-isobutyrylamino-34-isopropyl-31,37 -dimethyl-10,16,19,22,30,32,35,38-octaoxo-36-oxa-9,11,17,20,23,28, 31,33-octaazatetracyclo[16.13.6.1(24),(28).0(3),(8)]octatricont a-3,5,7-trien-5,6-diyl disulfate, is a water-soluble inhibitor of human neutrophil elastase with a molecular mass of 1166.15 Da. FR134043 demonstrated a characteristic competitive inhibition of human neutrophil elastase with a Ki of 8 nM. In studies using synthetic substrates, FR134043 inhibited both neutrophil elastase activity and porcine pancreatic elastase activity with IC50 values of 35 nM and 49 nM respectively. FR134043 also inhibited hydrolysis of bovine neck ligament elastin by human neutrophil elastase with an IC50 value of 210 nM. In in vivo experiments, FR134043 protected animals against human neutrophil elastase (50 microg/animal)-induced lung hemorrhage in hamsters with an ED50 value of 3.1 microg/animal for intratracheal administration and 5.0 mg/kg for intravenous administration. Subcutaneous treatment with FR134043 significantly suppressed human neutrophil elastase (20 microg/paw)-induced paw edema in mice with an ED50 value of 3.3 mg/kg when evaluated 4 h after elastase injection. The potency of FR134043 given intratracheally to protect against porcine pancreatic elastase (100 microg/animal)-induced emphysema in hamsters was relatively low (Quasi-static lung compliance; ED50 = 1590 microg/animal) compared to that in acute animal models. FR134043 (10 mg/kg per h i.v. infusion) significantly improved lipopolysaccharide (0.25 mg/kg per h i.v. infusion)-induced thrombocytopenia and some coagulation parameters in rats. These results suggest that systemic administration of FR134043 would be advantageous over intratracheal administration of FR134043 for the treatment of adult respiratory distress syndrome, septic shock and pulmonary emphysema and other pathophysiologic conditions in which elastases are thought to be involved.

Animals↗

Guanylate-cyclase-inhibitory protein is a frog retinal Ca2+-binding protein related to mammalian guanylate-cyclase-activating proteins.

Two guanylate-cyclase-activating proteins (GCAP) encoded by a tail-to-tail gene array have been characterized in the mammalian retina. Using frog retina as a model, we obtained evidence for the presence of a photoreceptor Ca2+-binding protein closely related to GCAP. This protein (206 amino acids) does not stimulate guanylate cyclase (GC) in low [Ca2+], but inhibits GC in high [Ca2+], and is therefore termed guanylate-cyclase-inhibitory protein (GCIP). Sequence analysis indicates that GCIP and GCAP1 and GCAP2 have diverged substantially, but conserved domains present in all vertebrate GCAP are present in GCIP. Moreover, partial characterization of the GCIP gene showed that the positions of two introns in the GCIP gene are identical to positions of corresponding introns of the mammalian GCAP gene array. As to the major differences between GCIP and GCAP, the fourth EF hand Ca2+-binding motif of GCIP is disabled for Ca2+ binding, and GCIP does not stimulate GC. Monoclonal and polyclonal antibodies raised against recombinant GCIP identified high levels of GCIP in the inner segments, somata and synaptic terminals of frog cone photoreceptors. The results suggest that GCIP is a Ca2+-binding protein of the GCAP/recoverin subfamily. Its localization in frog cones closely resembles that of GC in mammalian cones. GCIP inhibits GC at high free [Ca2+], competing with GCAP1 and GCAP2 for GC regulatory sites.

Amino Acid Sequence↗

Determination of the depth of penetration of the alpha subunit of retinal G protein in membranes: a spectroscopic study.

This paper reports the fluorescence quenching of the alpha subunit of retinal rod outer segment G protein (Gtalpha) by vesicles of brominated phospholipids. Two different brominated phospholipids with the bromine quencher groups attached at the 6-7 and 9-10 positions in one of the fatty acyl chains have been used to estimate the depth of penetration of the Gtalpha protein in the lipid vesicles using steady-state fluorescence quenching techniques. Our studies provide evidence of the interaction between Gtalpha protein, in its active conformation, with the lipid vesicles mimicking natural membranes. This study demonstrates that in vitro the distance between fluorescent tryptophan site of Gtalpha and the membrane surface is approximately 6.5 A.

Animals↗

[Resection of asymptomatic infected bulla associated with pulmonary tuberculosis].

The patient was a 49-year-old man. A physical examination in 1995 had disclosed the presence of a bulla in his left lung. Chest x-ray films taken in February 1997 disclosed niveau formation as an abnormal shadow in contact with the bulla. The patient was given a diagnosis of an infected bulla, and underwent an operation for partial resection of the S 6 portion of the left lung. The intracystic fluid was serous and no general bacteria or mycobacteria were detected. However, histopathological examination found granulation tissue associated with caseous necrosis and containing mycobacteria. The patient is currently receiving tuberculostatic agents on an outpatient basis.

Blister↗

[Three cases of pulmonary dirofilariasis suspected of lung cancer].

We experienced with three patients with pulmonary dirofilariasis found in resected lungs. Two patients showed abnormal shadows on chest roentgenograms without symptoms. Another patients had chest discomfort. All patients underwent diagnostic thoracotomy. Histopathological examination showed necrotic granulomatous lesions surrounded by fibrous tissue and transverse section of Dirofilaria immits was found. It has been an increasing reported disease. It is important to keep in mind the possibility of dirofilariasis.

Adolescent↗

[A case of mediastinal cavernous hemangioma resected through thoracoscope].

A case of mediastinal cavernous hemangioma was reported. An abnormal shadow on the chest X-ray film was pointed out in a 55-year-old male. CT scan and MRI revealed a right posterior mediastinal tumor but did not aid in the final diagnosis. We underwent extirpation of the tumor through thoracoscope and confirmed to be a cavernous hemangioma histologically. No major vascular connections between the tumor and major vessels were found. It was useful of thoracoscopic surgery in this case.

Endoscopy↗

Biochemical and pharmacological characterization of FK706, a novel elastase inhibitor.

FK706, sodium 2-[4-[[(S)-1-[[(S)-2-[[(RS)-3, 3, 3-trifluoro-1-isopropyl-2-oxopropyl]aminocarbonyl]pyrrolidin -1-yl]carbonyl]-2-methylpropyl] aminocarbonyl] benzoylamino] acetate, C26H32F3N4NaO7, is a synthetic water-soluble inhibitor of human neutrophil elastase. This compound demonstrated a competitive and slow-binding inhibition of human neutrophil elastase with a Ki of 4.2 nM. In studies using synthetic substrates, FK706 inhibited human neutrophil elastase activity and porcine pancreatic elastase activity with respective IC50 values of 83 and 100 nM. FK706, however, inhibited more weakly, (IC50 values > 340 microM) other serine proteinases such as human pancreatic alpha-chymotrypsin, human pancreatic trypsin and human leukocyte cathepsin G. FK706 also effectively inhibited the hydrolysis of bovine neck ligament elastin (2 mg/ml final concentration) by human neutrophil elastase (4 microg/ml final concentration) with an IC50 value of 230 nM. FK706 protected animals against human neutrophil elastase (50 microg/animal)-induced lung hemorrhage with ED50 values of 2.4 microg/animal by intratracheal administration and 36.5 mg/kg by intravenous administration, respectively. Subcutaneous administration of FK706 significantly suppressed human neutrophil elastase (20 microg/paw)-induced paw edema in mice in a dose-dependent manner (47% inhibition at a dose of 100 mg/kg). These results suggest that FK706 would be a useful tool for investigating the role of human neutrophil elastase in inflammatory disorders associated with an excess of elastase, such as pulmonary emphysema, adult respiratory distress syndrome, septic shock, cystic fibrosis, chronic bronchitis and rheumatoid arthritis.

Animals↗

Residues within the polycationic region of cGMP phosphodiesterase gamma subunit crucial for the interaction with transducin alpha subunit. Identification by endogenous ADP-ribosylation and site-directed mutagenesis.

Interaction between the gamma subunit (Pgamma) of cGMP phosphodiesterase and the alpha subunit (Talpha) of transducin is a key step for the regulation of cGMP phosphodiesterase in retinal rod outer segments. Here we have utilized a combination of specific modification by an endogenous enzyme and site-directed mutagenesis of the Pgamma polycationic region to identify residues required for the interaction with Talpha. Pgamma, free or complexed with the alphabeta subunit (Palphabeta) of cGMP phosphodiesterase, was specifically radiolabeled by prewashed rod membranes in the presence of [adenylate-32P]NAD. Identification of ADP-ribose in the radiolabeled Pgamma and radiolabeling of arginine-replaced mutant forms of Pgamma indicate that both arginine 33 and arginine 36 are similarly ADP-ribosylated by endogenous ADP-ribosyltransferase, but only one arginine is modified at a time. Pgamma complexed with Talpha (both GTP- and GDP-bound forms) was not ADP-ribosylated; however, agmatine, which cannot interact with Talpha, was ADP-ribosylated in the presence of Talpha, suggesting that a Pgamma domain containing these arginines is masked by Talpha. A Pgamma mutant (R33,36K), as well as wild type Pgamma, inhibited both GTP hydrolysis of Talpha and GTP binding to Talpha. Moreover, GTP-bound Talpha activated Palphabeta that had been inhibited by R33,36K. However, another Pgamma mutant (R33,36L) could not inhibit these Talpha functions. In addition, GTP-bound Talpha could not activate Palphabeta inhibited by R33,36L. These results indicate that a Pgamma domain containing these arginines is required for its interaction with Talpha, but not with Palphabeta, and that positive charges in these arginines are crucial for the interaction.

3',5'-Cyclic-GMP Phosphodiesterases↗

[A self-conceptual descriptive study of childrearing women and their family--analyses of "the self as a mother" and "the self as an individual with a life of their own"].

A retrospective exploratory-descriptive design was used to describe the modern Japanese women's self-concept during the early stages of childrearing. The purpose of this research was to explore how a Japanese woman's self-concept changes after she becomes a mother. Seven women, aged 28 to 38, from a purpose sample, were interviewed at home using the-semi-structured interview guide. The core category, "someone needs me", provided the more significant indicator of women's self-concept, reflecting the importance of their existence to others. Findings indicated that the modern Japanese woman seeks to be needed by two parties: their children and society. One of these needs originates in the self as a mother. The other originates in the self as an individual with a life of their own. In the acceptance, through family life, of the fulfillment of the two selves,: "myself needed by my child" and "myself needed by society", the self-concept of modern Japanese women during the early stages of childrearing was defined.

Adult↗

Physeal surgery: indications and operative treatment.

The evaluation and treatment of problems that can be corrected by surgery on the growth plate have changed somewhat in recent years; therefore, it is the purpose of this article to update the reader on these advances, as well as review the basic concepts. We review the radiographic evaluation of problems in the extremities and detail key points of physeal operative techniques for correcting problems occurring with growth.

Growth Plate↗

Possible stimulation of retinal rod recovery to dark state by cGMP release from a cGMP phosphodiesterase noncatalytic site.

Cyclic GMP phosphodiesterase, a key enzyme for phototransduction, contains alpha, beta (Palphabeta), and two gamma (Pgamma) subunits. In addition to catalytic sites, Palphabeta has two classes of noncatalytic cGMP binding sites with different affinities (Kd values <100 nM and >1 microM). Pgamma regulates Palphabeta as an inhibitor of cGMP hydrolysis and as a stimulator of cGMP binding to the high affinity noncatalytic sites. Pgamma release from Palphabeta by the GTP-bound alpha subunit of transducin (GTP.Talpha) interrupts these two functions. Here we describe a novel regulation of the Pgamma release by [cGMP] and its physiological implication. We isolated Pgamma mutants that exhibit abnormally one of these two functions, indicating the distinct domains in Pgamma are involved to express these functions. When [cGMP] was high ( approximately 5 microM), Pgamma responsible for the inhibition of cGMP hydrolysis was preferentially released, and cGMP hydrolysis activity of Palphabeta was increased about 10 times. When [cGMP] was low (less than approximately 0.5 microM), Pgamma responsible for the stimulation of cGMP binding to the high affinity sites was released. The Pgamma release resulted in the decrease of relative affinity of cGMP for the high affinity sites to at least (null)/1;10, followed by the rapid release of cGMP from one of the high affinity sites (apparent t1/2 = 3.8 s). cGMP ( approximately 5 microM) inhibited the extraction of Palphabeta from rod membranes by a Mg2+-free hypotonic buffer. The inhibition of Palphabeta extraction was not affected by Pgamma, suggesting that Palphabeta detects on the order of micromolar [cGMP] using low affinity noncatalytic sites on Palphabeta. Because [cGMP] is approximately 5 microM in darkness and lowered by photoexcitation and phosphodiesterase concentration is approximately 30 microM in rod photoreceptors, it is possible that cGMP phosphodiesterase functions to increase cytoplasamic [cGMP] after [cGMP] is reduced to the illuminated level.

3',5'-Cyclic-GMP Phosphodiesterases↗

Discrimination of two functions of photoreceptor cGMP phosphodiesterase gamma subunit.

cGMP phosphodiesterase, a key enzyme in phototransduction, is composed of P alpha beta and two P gamma S. P gamma has two functions in P alpha beta regulation: (I) an inhibitor of cGMP hydrolysis and (II) a stimulator of cGMP binding to their noncatalytic sites. Here we show for the first time that these functions can be discriminated. P gamma release by GTP-bound transducing from P alpha beta was stimulated by NaCl in a concentration-dependent manner. However, phosphodiesterase activity in membranes washed with NaCl-free buffer already reached the maximum level. [3H]-cGMP binding of P alpha beta in membranes washed with NaCl required more P gamma than that in membranes washed without NaCl. Other salts had a similar effect. Identical P gamma was released under different [NaCl]. These results indicate that P gamma for the function (I) is released in low [salt], but P gamma for the function (II) is released in high [salt]. These P gamma functions may be expressed separately in phototransduction.

3',5'-Cyclic-GMP Phosphodiesterases↗

Enhancement of brain noradrenaline and dopamine turnover by thyrotropin-releasing hormone and its analogue NS-3 in mice and rats.

The effects of intravenous injections of thyrotropin-releasing hormone and its analog NS-3 (montirelin hydrate, CG3703) on the dynamics of brain monoamines were examined in mice and rats. In mice, both NS-3 (0.1-1 mg/kg) and thyrotropin-releasing hormone (10 and 30 mg/kg) increased the concentrations of 4-hydroxy-3-methoxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid. The turnover rates, estimated either by depletion of catecholamines after treatment with alpha-methyl-p-tyrosine or by probenecid-induced accumulation of homovanillic acid, were enhanced by these peptides. In contrast, none of the compounds had any influence on the serotonin turnover. In rats, both NS-3 and thyrotropin-releasing hormone produced a regionally specific increase in the concentrations of the catecholamine metabolites. A microdialysis study demonstrated that NS-3 significantly increased the release of dopamine in the nucleus accumbens as well as the striatum of conscious rats, while thyrotropin-releasing hormone caused a weak but significant enhancement of dopamine release only in the nucleus accumbens. These findings indicate that NS-3 was far more potent than thyrotropin-releasing hormone in facilitating the turnover of catecholamines without affecting serotonin turnover in the mouse and rat brain.

Animals↗