PubMed Health⌕ Search

Biomedical subjects

Y Sudo

Publications and source records attributed to Y Sudo.

At least 127 records · Page 7Linked to original sources
PubMed1992

Palmitoylation alters protein activity: blockade of G(o) stimulation by GAP-43.

The addition of palmitate to cysteine residues enhances the hydrophobicity of proteins, and consequently their membrane association. Here we have investigated whether this type of fatty acylation also regulates protein-protein interactions. GAP-43 is a neuronal protein that increases guanine nucleotide exchange by heterotrimeric G proteins. Two cysteine residues near the N-terminus of GAP-43 are subject to palmitoylation, and are necessary for membrane binding as well as for G(o) activation. N-terminal peptides, which include these cysteines, stimulate G(o). Monopalmitoylation reduces, and dipalmitoylation abolishes the activity of the peptides. The activity of GAP-43 protein purified from brain also is reversibly blocked by palmitoylation. This suggests that palmitoylation controls a cycle of GAP-43 between an acylated, membrane-bound reservoir of inactive GAP-43, and a depalmitoylated, active pool of protein.

Animals↗
PubMed1992

The effect of FK664, a new cardiovascular drug, on systemic capacitance vessels in anesthetized dogs.

To characterize the cardiovascular effect of FK664, a compound developed for the treatment of heart failure, the mean circulatory pressure (MCP), cardiac output and other parameters were measured in open-chest anesthetized dogs. Milrinone, a cardiotonic agent, and nifedipine, a calcium channel blocker were used as reference substances. Nifedipine (10 micrograms/kg), FK664 (0.1 mg/kg) or milrinone (0.1 mg/kg) given intravenously reduced the total peripheral resistance in a similar extent (35-40%). Whereas nifedipine had no effect on MCP, FK664 produced a significant decrease in MCP. Milrinone caused a minimal decrease in MCP, but not significantly. These results indicate that FK664 dilates the systemic capacitance vessels. This action to reduce the pre-load would be beneficial in the treatment of heart failure.

Animals↗
PubMed1992

Improved heart failure protection by FK664, a novel positive inotropic agent, in dog heart-lung preparations.

The effects of FK664, a novel positive inotropic agent, and enoximone on pentobarbital-induced heart failure were compared in dog heart-lung preparations. Both FK664 and enoximone improved the cardiac function curve in a dose-dependent manner and restored it to the control level at drug concentrations of 1 microgram/ml and 10 micrograms/ml, respectively. Therefore, the cardiotonic potency of FK664 appears to be 10 times that of enoximone. These agents were almost equal in force-rate separation of cardiac effect. Neither of the agents produced arrhythmia at any dose tested. These results suggest that FK664 may be a potent cardiotonic agent for the treatment of heart failure.

Animals↗
PubMed1992

Wegener's granulomatosis in a patient with a rheumatoid arthritis.

A 38-year-old woman with rheumatoid arthritis who developed Wegener's granulomatosis is described. Wegener's granulomatosis appeared with saddle nose, perforation in her nasal septum, and granuloma in the nasal cavity. Laboratory evaluation showed a positive rheumatoid factor and circulating immune complex. Radiographic examination revealed ankylotic changes in both wrist and elbow joints. Bilateral anosmia and other disease manifestations completely responded to treatment with oral cyclophosphamide and prednisolone.

Adult↗
PubMed1992

[Study on the pharmacokinetics of cefepime (I)].

The pharmacokinetics of 14C-cefepime dihydrochloride (14C-CFPM), were studied in rats upon both single and repeated intravenous administration. 1. Blood level of radioactivity was 59.27 micrograms eq./ml at 5 minutes after single intravenous administration at a dose of 20 mg/kg, and declined biexponentially thereafter. The values of AUC and T 1/2 were 70.1 micrograms eq..hr/ml and 38.0 hours, respectively. 2. Blood level of radioactivity was 59.41 micrograms eq./ml at 5 minutes after administration on the 7th day of repeated intravenous administration at a daily dose of 20 mg/kg, and declined more slowly as compared to the case of single administration. The values of AUC and T 1/2 after repeated administration were 159.7 micrograms eq..hr/ml and 44.5 hours, respectively. 3. Urinary and fecal excretion rates after single administration were 93.3% and 3.3%, respectively. 4. Urinary and fecal excretion rates were almost constant throughout the repeated administration; 88.4-90.7% and 2.3-3.7%, respectively. 5. 14C-CFPM distributed rapidly to the whole body except to the central nervous system. Although the radioactivity was removed rapidly from tissues, high levels of radioactivity remained in the kidney and the spleen as compared to other tissues. 6. Tissue concentrations of radioactivity at 5 minutes after the final dose of repeated administration were about the same as those after single administration but they declined more slowly than those after single administration. High levels of radioactivity were found in the kidney and the spleen as were found upon single administration. The ratios of these levels between repeated and single dosing were 4.3 and 2.6 for kidney and spleen, respectively. 7. Data obtained with autoradiograms of the whole body were consistent with measured tissue distribution obtained in both cases of single and repeated administration.

Animals↗
PubMed1992

[Study on the pharmacokinetics of cefepime (II)].

The pharmacokinetics of 14C-cefepime dihydrochloride (14C-CFPM), was studied in dogs after single intravenous administration at a dose of 20 mg/kg. Protein binding was also investigated both in vitro and in vivo. 1. Blood level of radioactivity was 83.53 microns eq./ml at 5 minutes after single intravenous administration and declined biexponentially thereafter. The values of AUC and T1/2 were 229 microns eq.(.)hr/ml and 90 hours, respectively. 2. Urinary and fecal excretion rates were 95.1% and 2.7%, respectively. 3. The in vitro protein binding at 1 to 100 microns/ml of drug concentration was 7.9 to 12.7% in rat, 12.4 to 18.6% in human, and 12.5 to 14.5% in dog. In vivo protein binding, which increased with time after administration, was 10.8 to 92.9% in rat and 17.5 to 64.9% in dog at 5 minutes to 6 hours.

Animals↗
PubMed1992

[Two separate surgical repairs of post-infarction blowout rupture of the left ventricular free wall and subsequently developed subepicardial aneurysm].

A 69-year-old female patient with acute myocardial infarction was admitted to our hospital. After i.v. administration of the rt-PA, echocardiography disclosed pericardial effusion to which pericardial drainage was performed first through subxiphoid incision. Immediately after the drainage, electromechanical dissociation emerged and emergency thoracotomy was performed. There was a small blowout rupture of the left ventricular free wall that was successfully repaired using single suture buttressed with Dacron felt without cardiopulmonary bypass support. On the 38th day after the surgery, cineangiography disclosed ventricular aneurysm, to which aneurysmectomy was performed under the cardiopulmonary bypass and her post operative progress was uneventful. Histological study of the resected specimen revealed so called subepicardial aneurysm. Although blowout rupture of the left ventricular free wall used to be lethal, there might be a chance of life saving even without cardiopulmonary bypass support, if the left thoracotomy could be done as quickly as possible.

Aged↗
PubMed1992

[A case of supravalvular pulmonary stenosis associated with Noonan's syndrome: usefulness of Doty's operation].

A twelve-year-old boy associated with Noonan's syndrome is reported. He had supravalvular pulmonary stenosis with a very high right-ventricular pressure, higher than that of systemic. Surgical treatment was performed to the supravalvular pulmonary stenosis with the technique of Doty's operation for supravalvular aortic stenosis, brought an excellent results. The gradient between the right ventricle and the pulmonary artery fell from 97 mmHg to 30 mmHg. The residual gradient is caused by functional infundibular stenosis. Doty's operation is a useful method for the operation of severe supravalvular pulmonary stenosis, too.

Aortic Valve Stenosis↗
PubMed1991

An intracellular guanine nucleotide release protein for G0. GAP-43 stimulates isolated alpha subunits by a novel mechanism.

G protein-coupled membrane receptors activate G proteins by enhancing guanine nucleotide exchange. G0 is a major component of the growing regions (growth cones) of neurons. GAP-43 is a neuronal protein associated with the cytosolic face of the growth cone plasma membrane and stimulates binding of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) to Go (Strittmatter, S. M., Valenzuela, D., Kennedy, T. E., Neer, E. J., and Fishman, M. C. (1990) Nature 344, 836-841). Here we have examined the mechanism by which GAP-43 affects G0. Like G protein-coupled receptors, GAP-43 enhances GDP release from G0, increases the initial rate of GTP gamma S binding, and increases the GTPase activity of Go, all without altering the intrinsic kappa cat for the GTPase. Unlike the case for receptors, however, the GAP-43 effect is not blocked by pertussis toxin, nor affected by the presence or absence of beta gamma or of phospholipids. There is specificity to the interaction, in that GAP-43 increases GTP gamma S binding to recombinant alpha o and alpha i1, but not to recombinant alpha s. Thus, GAP-43 is a guanine nucleotide release protein with a novel mechanism of action, potentially controlling membrane-associated G proteins from within the cell.

Animals↗
PubMed1991

Growth cone transduction: Go and GAP-43.

The neuronal growth cone plays a crucial role in forming the complex brain architecture achieved during development, and similar nerve terminal mechanisms may operate to modify synaptic structure during adulthood. The growth cone leads the elongating axon towards appropriate synaptic targets by altering motility in response to a variety of extracellular signals. Independently of extrinsic clues, neurons manifest intrinsic control of their growth and form (Banker and Cowan, 1979). Hence, there must be intracellular proteins which control nerve cell shape, so-called 'plasticity' or 'growth' genes. GAP-43 may be such a molecule (Skene and Willard, 1981; Benowitz and Lewis, 1983). For example, GAP-43 is localized to the growth cone membrane (Meiri et al. 1986; Skene et al. 1986) and can enhance filopodial formation even in non-neuronal cells (Zuber et al. 1989a). It includes a small region at the amino terminus for membrane association and perhaps growth cone targeting (Zuber et al. 1989b, Liu et al. 1991). We have found that Go, a member of the G protein family that links receptors and second messengers, is the major non-cytoskeletal protein in the growth cone membrane (Strittmatter et al. 1990). Double staining immunohistochemistry for GAP-43 and Go shows that the distributions of the two proteins are quite similar. Purified GAP-43 regulates the activity of purified Go (Strittmatter et al. 1990), a surprising observation since GAP-43 is an intracellular protein. We have compared the mechanism of GAP-43 activation of Go with that of G protein-linked receptors.2+ interactions between Go and GAP-43 suggest that Go plays a pivotal role in growth cone function, coordinating the effects of both extracellular signals and intracellular growth proteins.

Animals↗
PubMed1991

[A case of successful surgical treatment of recrudescent Stanford type A--acute dissection after early thrombogenic closure of dissecting lumen].

A 53-year-old woman was hospitalized with acute chest pain. A CT scan was demonstrated acute type A aortic dissection. The dissecting lumen was already closed with thrombus. A digital subtraction angiography was performed. It showed no intimal tear and a normal aortic figure. She received the medical treatment. On the fourteenth day after her admission, her both femoral arterial pulses were not palpable. A CT scan and an angiogram were performed. The new intimal tear in the ascending aorta was made, and pericardial effusion appeared. With the use of a ringed interluminal graft, an emergency operation was performed. She was discharged in good health. Some cases of early thrombogenic closure of the dissecting lumen in acute aortic dissection were reported. In a few of them, a new intimal tear developed and they lapsed into the recrudescent acute dissection. Thus, more careful medical follow up is necessary in these cases.

Acute Disease↗
PubMed1991

[Clinical experience of the Greenfield filter--especially about tilting and distal migration of the filters].

Since December 1985, we used Greenfield filter in 8 patients to prevent pulmonary embolism. Mean follow-up period was 42 month. Recurrence of pulmonary embolism was suspected in one patient after perfusion lung scan. Another patient died from other reasons. Occlusion of the inferior vena cava was not suspected in any patient clinically. Tilting and distal migration of the filters occurred frequently. 3 filters tilted greater than 5 degrees compared with the position immediately after their placement. 5 filters migrated distally more than half the length of a lumbar vertebra. Although there was no severe complications in our series, we should pay attention especially to the position and angle of the filters, since an extreme tilting position of the filter could be a possible cause of serious complications.

Adult↗
PubMed1991

[Two reoperative cases of annuloaortic ectasia with Cabrol's method].

Two reoperative cases of annuloaortic ectasia are reported. Since they have problems such as adhesion and friability of tissues, bleeding from each anastomosed sites must be watched carefully. Especially, anastomoses of aortic annulus and the composite graft, coronary ostia and the interposed conduit are important. Appropriate anastomosis of aortic annulus needs flexibility at the proximal edge of the composite graft. It can be achieved by sewing Björk-Shiley prosthetic valve about 5 mm distant from the proximal edge of the composite graft. Cabrol's method is good for anastomoses of coronary ostia because easily visualized and less stressed anastomoses can be performed. Therefore Cabrol's method with flexible edge of the composite graft at the proximal site is a useful technique in the reoperation of annuloaortic ectasia.

Anastomosis, Surgical↗
PubMed1991

[A case report of early prosthetic valve endocarditis due to methicillin resistant Staphylococcus aureus infection--an experience of intraatrial implantation of mitral prosthesis with a Gore-Tex flange].

A 60-year-old female with mitral stenosis developed prosthetic valve endocarditis due to methicillin resistant staphylococcus aureus septicemia 3 weeks after mitral valve replacement. In vitro test disclosed susceptibility to minocycline and clindamycin. Despite large amount of intravenous administration, progressive heart failure due to massive perivalvular leakage occurred as a consequence of persisting infection. An emergent operation revealed valve detachment of the posterior portion resulting from ring abscess formation. A mitral prosthesis with a Gore-Tex flange was implanted partially in the left atrium just above the mitral ring and sutured to the atrial wall. Postoperative relapse was not detected even after discontinuing antibiotics. Prosthetic valve endocarditis due to methicillin resistant staphylococcus aureus is highly resistant to antibiotic therapy and likely to develop valve ring abscess. Prompt surgical treatment is mandatory in this situation.

Endocarditis, Bacterial↗
PubMed1990

Enzymic conversion of alpha-oxyprotohaem IX into biliverdin IX alpha by haem oxygenase.

Conversion of four isomers of meso-oxyprotohaem IX into the corresponding biliverdin IX was attempted with a reconstituted haem oxygenase system in the presence of NADPH-cytochrome c reductase and NADPH. Only the alpha-isomer of meso-oxyprotohaem IX was converted effectively into biliverdin IX alpha, which was further reduced to bilirubin IX alpha by biliverdin reductase. Only trace amounts of biliverdins IX beta, IX gamma and IX delta were respectively formed from the incubation mixture of the corresponding oxyprotohaemin IX isomers with the complete haem oxygenase system under the same conditions. In a kinetic study, the Km for alpha-meso-oxyprotohaem IX was 3.6 microM, which was 2-fold higher than that for protohaem IX. The maximum velocity (Vmax.) of the conversion of alpha-meso-oxyprotohaem IX into biliverdin IX alpha was twice as fast as that of protohaem IX. These results demonstrate that alpha-meso-oxyprotohaem IX is an intermediate of haem degradation and it was converted stereospecifically into biliverdin IX alpha via verdohaem IX alpha.

Animals↗
PubMed1990

Antitumor activity of a derivative of mitomycin, 7-N-[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), against murine and human tumors and a mitomycin C-resistant tumor in vitro and in vivo.

The antitumor activity of a mitomycin derivative, 7-N-[2[[2-(gamma-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), was evaluated in murine and human tumor models, including a mitomycin C (MMC)-resistant tumor in vitro and in vivo. KW-2149 showed a profound effect against i.p. inoculated P388 leukemia on both a single and an intermittent administration schedule. Against s.c. implanted colon adenocarcinoma 38 (colon 38). KW-2149 was as effective as MMC in ILS% and in tumor growth inhibition on a single-administration schedule. Both compounds were similarly effective when an intermittent schedule was used. KW-2149 showed activity against human tumor xenografts and was effective in two of four non-small-cell lung carcinomas but was not effective against three gastric adenocarcinomas on the single-administration regimen. The activity of KW-2149 against gastric adenocarcinoma was inferior to that of MMC on a single-administration schedule. However, the antitumor activity of KW-2149 was higher on an intermittent schedule than on a single-administration regimen. The antitumor activity of KW-2149 against human tumor xenografts was similar to that of MMC on an intermittent schedule, and the former drug was effective against both gastric adenocarcinomas and both non-small-cell lung carcinomas. KW-2149 was more effective than MMC against a subline of P388 leukemia that is resistant to MMC in vitro as well as in vivo.

Adenocarcinoma↗