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Biomedical subjects

S Miki

Publications and source records attributed to S Miki.

At least 37 records · Page 2Linked to original sources
PubMed1999

Small amino acid changes in the V3 loop of human immunodeficiency virus type 2 determines the coreceptor usage for CXCR4 and CCR5.

HIV-2 GH-1 is a molecular clone derived from an AIDS patient from Ghana. In contrast to the prototypic molecular clone ROD, GH-1 exhibits a narrow range of target cell specificity. By an infectious assay using HeLa-CD4 cells stably transfected with an HIV-1 LTR-beta-galactosidase reporter gene and transiently expressing various cloned chemokine receptors, we have examined the coreceptor usage of GH-1. In contrast to ROD, which uses principally CXCR4, GH-1 was found to use mainly if not exclusively CCR5 but not CXCR4. The distinct coreceptor usage of these two molecular clones allowed us to further map the region of gp120 that is important for the coreceptor specificity. By constructing a series of chimeric viruses between GH-1 and ROD, we have demonstrated that the C-terminal half of the V3 loop region of gp120 determines the differential coreceptor usage between GH-1 and ROD, and only a few amino acid differences in this region appear to be able to shift the specificity between CCR5 and CXCR4. Notably, the shift in the coreceptor usage from CCR5 to CXCR4 is associated with an increase in the net positive charge in the V3 region.

Acquired Immunodeficiency Syndrome↗
PubMed1999

High origin of the right coronary artery with congenital heart disease.

We encountered a case of anomalous high origin of the right coronary artery associated with ventricular septal defect and patent ductus arteriosus. The right coronary artery originated from the distal part of the ascending aorta resulting in unsuccessful induction of cardiac arrest by cardioplegia. We describe this rare case with anomalous origin of the right coronary artery.

Aorta↗
PubMed1999

Distance between mitral anulus and papillary muscles: anatomic study in normal human hearts.

BACKGROUND: Preservation of the annulo-papillary muscle continuity in mitral valve replacement is important. Even in patients who require excision of the mitral apparatus, the continuity can be restored. However, there is no guide to the proper length for the resuspension. METHODS: In 57 normal cadaveric hearts, the distance from the tip of the papillary muscle to its corresponding mitral anulus was directly measured. RESULTS: The distance from the tip of the anterolateral papillary muscle to the left trigone (10-o'clock position: D10) and to the point between the anterior and the middle scallops of the mural leaflet (8-o'clock position: D8) was 23.5 +/- 3.7 mm and 23.2 +/- 3.6 mm, respectively. The distance from the tip of the posteromedial papillary muscle to the right trigone (2-o'clock position: D2) and to the point between the middle and the posterior scallops of the mural leaflet (4-o'clock position: D4) was 23.5 +/- 4.0 mm and 23.5 +/- 3.9 mm, respectively. There was no statistically significant difference among the 4 distances (P =.96). Each distance was significantly longer than the corresponding chordae tendineae (D10 vs the anterior main chorda: 17.2 +/- 3.9 mm, D8 vs the anterior cleft chorda: 14.5 +/- 3.2 mm, D2 vs the posterior main chorda: 17.9 +/- 4.3 mm, and D4 vs the posterior cleft chorda: 14.9 +/- 3.2 mm, respectively; P =.0001). The mean distance had a significant correlation with the mitral annular diameter (r = 0.31, P =.019). CONCLUSIONS: In normal hearts, the annulo-papillary muscle distances of the mitral apparatus are similar in 2-, 4-, 8-, and 10-o'clock positions and correlate with the mitral annular diameter.

Adult↗
PubMed1999

Evolutionary molecular engineering by random elongation mutagenesis.

We describe a new method of random mutagenesis that employs the addition of peptide tails with random sequences to the C-terminal of enzyme molecules. A mutant population of catalase I from Bacillus stearothermophilus prepared by this method has a diversity in thermostability and enzyme activity equal to that obtained after random point mutagenesis. When a triple mutant of catalase I (I108T/D130N/1222T)-the thermostability of which is much lower than that of the wild type-was subjected to random elongation mutagenesis, we generated a mutant population containing only mutants with higher thermostability than the triple mutant. Some had an even higher stability than the wild-type enzyme, whose thermostability is considered to be optimized. These results indicate that peptide addition expands the protein sequence space resulting in a new fitness landscape. The enzyme can then move along the routes of the new landscape until it reaches a new optimum. The combination of random elongation mutagenesis with random point mutagenesis should be a useful approach to the in vitro evolution of proteins with new properties.

Amino Acid Sequence↗
PubMed1999

Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome. Kansai-FGS-Apheresis Treatment (K-FLAT) Study Group.

BACKGROUND: The pathogenic role of hyperlipidemia in long-standing nephrotic syndrome (NS) is known to be responsible for both the progression of glomerulosclerosis and tubulointerstitial injury, especially in focal segmental glomerulosclerosis (FGS). METHODS: Aggressive lipid lowering treatment by low density lipoprotein (LDL) apheresis (LDL-A) using a dextran sulfate cellulose column to treat patients with steroid-resistant or frequently recurrent severe NS was performed first without fixing the protocol in eight patients with FGS and one with minimal change nephrotic syndrome (MCNS). The period of NS before LDL-A, number and average intervals of LDL-A until the end of the therapy, and the prognosis were investigated. Next, a multicenter study with a fixed protocol of LDL-A treatment was designed in combination with steroid therapy for treatment twice a week for three weeks and weekly for six weeks, and was performed in 17 patients with FGS. The effects on the state of NS in addition to the change of urinary eicosanoid metabolites and remission rates were evaluated. RESULTS: In the preliminary study, along with a rapid improvement of hyperlipidemia, a high incidence of remission was achieved by LDL-A performed at relatively short intervals. In the multicenter study with a fixed protocol, there was a significant decrease of urinary protein (P < 0.001) and increase of serum albumin (P < 0.02) as well as a decrease of thromboxane B2 (TXB2) excretion (P < 0.05) after the treatment. Urinary excretion of TXB2 was significantly reduced after LDL-A (P < 0.05). The rate of entering into complete or incomplete remission was 71% with a relatively short duration of nephrotic-range proteinuria using the LDL-A therapy in comparison with steroid therapy alone. CONCLUSION: The rapid improvement of hypercholesterolemia with LDL-A treatment may provide a new approach for a high rate of improvement in the degree of NS in steroid-resistant NS of FGS and MCNS.

Adolescent↗
PubMed1999

Central effects of endothelin and its antagonists on sympathetic and cardiovascular regulation in SHR-SP.

Intracerebroventricular injections of endothelin-1 (ET-1) are reported to cause dose-related increases in sympathetic nerve activity and blood pressure in anesthetized normotensive rats. These studies were performed to determine the following: which endothelin receptor, A or B, is involved in mediating sympathetic and cardiovascular effects of ET-1 injected centrally; whether central endothelin tonically participates in blood pressure regulation in normotensive rats; and whether the altered endothelin system in the central nervous system contributes to blood pressure elevation in hypertensive rats. ET-1, ET-A antagonist (BQ-123), or ET-B antagonist (RES-701-1) was injected into the lateral cerebral ventricle (i.c.v.) of urethane-anesthetized normotensive Wistar and Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHRs), and stroke-prone SHRs (SHR-SPs). In Wistar rats, i.c.v. injections of ET-1 (1, 5, 10 pmol) consistently increased sympathetic nerve activity, thereby elevating blood pressure in a dose-related manner. The pressor responses induced by i.c.v. ET-1 were abolished after intravenous pretreatment with phentolamine. Neither ET-A nor ET-B antagonist, when injected centrally, altered basal levels of sympathetic nerve activity, heart rate, or blood pressure in Wistar rats. However, sympathetic activation and pressor responses induced by i.c.v. injection of endothelin were completely abolished after i.c.v. pretreatment with ET-A antagonist but were unaffected after pretreatment with ET-B antagonist. Although i.c.v. injections of ET-1 increased sympathetic nerve activity and blood pressure in WKY rats, SHRs, and SHR-SPs, the magnitudes of these responses did not differ among these three groups. In contrast, i.c.v. injections of ET-A antagonist decreased sympathetic nerve activity, blood pressure, and heart rate only in SHR-SPs, but not in WKY rats and SHRs. In addition, the depressor effects of i.c.v. ET-A antagonist in SHR-SPs were ascertained while these rats were awake. In summary, i.c.v. injections of ET-1 increased sympathetic nerve activity and blood pressure via ET-A receptors but not via ET-B receptors. Central ET might tonically activate sympathetic nerve activity to thereby contribute to blood pressure elevation in SHR-SPs, but not in WKY rats and SHRs.

Anesthesia↗
PubMed1999

Pressor response to compression of the ventrolateral medulla mediated by glutamate receptors.

The rostral ventrolateral medulla (RVLM) is considered a major center for the regulation of sympathetic and cardiovascular activities. Several clinical studies have indicated a possible causal relationship between neurovascular contact of the left RVLM and essential hypertension, and some investigators have suggested that the left RVLM is more sensitive to pulsatile compression than the right RVLM. Previously, we reported that pulsatile compression of the RVLM elevates arterial pressure by enhancing sympathetic outflow in rats; however, we have not investigated the laterality of the responses to the compression. In addition, it remains to be elucidated whether RVLM neurons are activated by compression and, if so, how they are activated. Therefore, we performed compression experiments in rats to investigate these issues. Pulsatile compression was performed on the unilateral RVLM with a pulsating probe in anesthetized and artificially ventilated rats. Pulsatile compression of the unilateral RVLM increased arterial pressure, heart rate, and sympathetic nerve activity. The pressor response to compression was inhibited significantly after local microinjection of glutamate receptor antagonists. Pulsatile compression of the RVLM increased Fos immunoreactivitiy, a marker of neuronal activation, within the nuclei of postsynaptic RVLM neurons. All results were observed symmetrically. The data indicate that the responses to pulsatile compression of the unilateral RVLM are similar on both sides. They also suggest that pulsatile compression of the RVLM increases sympathetic and cardiovascular activities by activating postsynaptic RVLM neurons through the stimulation of the local glutamate receptors in rats.

Animals↗
PubMed1999

Effect of histamine H2-receptor antagonist on the phosphorus-binding abilities of calcium carbonate and calcium lactate in hemodialysis patients.

The effect of histamine H2-receptor antagonist (famotidine) on the phosphorus-binding abilities of calcium carbonate and calcium lactate were examined in 13 chronic hemodialysis patients. In seven patients receiving calcium carbonate, famotidine (20 mg/d) was given because of gastroduodenal disorders, and calcium carbonate was replaced with calcium lactate as a phosphorus binder after 4 wk of treatment with famotidine. With the 4-wk administration of famotidine accompanied by calcium carbonate, the serum phosphorus level increased from 6.3+/-0.9 to 7.1+/-0.5 mg/dl (P<0.05). However, with the substitution of calcium lactate, the serum phosphorus level decreased significantly when compared to that before substitution (6.3+/-0.2 and 6.0+/-0.9 mg/dl after 4 and 8 wk of substitution, respectively), despite continued administration of famotidine. Serum calcium, creatinine, alkaline phosphatase, high sensitive parathyroid hormone, blood urea nitrogen, arterial blood pH, and bicarbonate were not significantly altered during the trial period. In six control patients treated with calcium carbonate alone, there were no statistical changes in serum calcium and phosphorus levels after substitution of calcium lactate for calcium carbonate. These results suggest that famotidine significantly affects the phosphorus-binding ability of calcium carbonate, but not that of calcium lactate. A careful observation of changes in the serum phosphorus level should be required in hemodialysis patients receiving calcium carbonate and histamine H2-receptor antagonists. Calcium lactate may be useful as a phosphorus binder in such hemodialysis patients.

Adult↗
PubMed1998

[Two surgical cases of right parasternal minimal incision for aortic valve replacement].

Although median sternotomy has been used as a good approach to all cardiac valves and coronary arteries, advantages of the minimal invasive cardiac operation have been reported recently. We employed the right parasternal minial incision, reported by Cosgrove et al. for two cases of aortic valve replacement. In the first case, we were able to get a good operation field and easily implanted a mechanical prosthesis. In contrast, we had some difficulties with the second case where in addition to the third and fourth cartilages, a second cartilage resection was necessary because the aortic root lay at a cephalic level. Moreover, the operation field was restricted because we left several rib cartilages to preserve the right internal thoracic artery. The cannula had to be inserted via the right atrium as we failed to insert it in the right femoral vein, and the aortic root deviated more medially than usual. From these experiences, it is important to check the position of aortic root, and if the cannula cannot be inserted in the femoral vein, cannulation via the right atrium can ve utilized in the minimal invasive cardiac operation.

Aortic Valve↗
PubMed1998

Two-stage repair for aortic regurgitation with interrupted aortic arch.

We performed two-stage repair for a rare adult case of interrupted aortic arch with aortic regurgitation and sinus of Valsalva aneurysm. A lateroisthmic bypass was established with minimal thoracotomy and partial clamping of the descending aorta to preserve collateral circulation. This was followed by aortic root reconstruction with a prosthetic graft and valve for aortic regurgitation with sinus of Valsalva aneurysm. This less invasive two-stage repair for such a rare pathology may facilitate smooth recovery of the patient.

Adult↗
PubMed1998

Unique association of pheochromocytoma with contralateral nonfunctioning adrenal cortical adenoma.

A 57-year-old woman complaining of hypertensive attacks associated with headache and palpitation was admitted to our hospital for examination of bilateral adrenal tumors in 1985. After right pheochromocytoma was diagnosed, right adrenalectomy was performed. The left adrenal tumor was small; thus, the left adrenal tumor was preserved to avoid adrenal insufficiency, although left adrenal pheochromocytoma could not be denied. In 1995, she was referred to our clinic again because of recurrent headache and palpitation, and enlargement of the left adrenal tumor. Although pheochromocytoma was suspected again, the enlarged left adrenal turned out to be a nonfunctioning cortical adenoma. This case was interesting, not only because of difficulty in identifying the left adrenal tumor, but also because of the rare coexistence of a pheochromocytoma and a nonfunctioning adrenal cortical tumor.

Adrenal Cortex Neoplasms↗
PubMed1998

Structural determination of metabolites of S-1153, a new, potent, non-nucleoside, anti-HIV agent in rat liver microsomes.

1. S-1153, a non-nucleoside agent that is under development in the USA as a new anti-HIV agent, has potent antiviral activity based on the inhibition of reverse transcriptase. 2. S-1153 was incubated with rat liver microsomes and NADPH, and seven metabolites were formed. The main metabolites were identified as the S-oxide, N-oxide and sulphone of S-1153. 3. Two other minor metabolites were assumed to be S-1153 hydroxylated on the isopropyl moiety. 4. Our findings confirmed the existence of at least three oxidative metabolic pathways of S-1153.

Animals↗
PubMed1998

Augmented response of endothelin-A and endothelin-B receptor stimulation in coronary arteries of hypertensive hearts.

To determine whether the vasoconstrictor response to endothelin-1 (ET-1) is altered in coronary vessels of hypertensive hearts and the role of ETA and ETB receptors in these responses to ET-1, the vasoconstrictor response to ET-1 in coronary vessels was measured with or without ETA and ETB receptor antagonists. In isolated hearts of spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat, the coronary perfusion pressure was measured on a Langendorff apparatus with constant pressure (75 mm Hg). Coronary perfusion resistance (CPR) (mm Hg/ml/min/g) was calculated. ET-1 elicited dose-dependent increases of CPR in both normotensive and SHR rat hearts. However, the responses were significantly greater in SHR than those of WKY. Pretreatment with the ETA antagonist FR139317 and the ETB antagonist BQ788 inhibited CPR increases with ET-1 infusion. However, vasoconstrictor responses to ET-1 were still greater in SHR than in WKY after FR139317 or BQ788 infusion. These findings suggest that the augmented vasoconstrictor response of coronary artery to ET-1 is mediated by both ETA and ETB receptors. These changes may contribute to the impaired coronary circulation in hypertension.

Animals↗
PubMed1998

Blockade of angiotensin II receptors inhibits the increase in blood pressure induced by insulin.

To elucidate whether hyperinsulinemia increases blood pressure by increasing sympathetic outflow via the activation of the central angiotensin system, insulin was infused into urethane-anesthetized rats intravenously (i.v.) or intracerebroventricularly (i.c.v.) under euglycemic conditions. Infusion (i.v.) of insulin elicited pressor effects in a dose-dependent manner (13, 20, and 40 mU/min). Although depressor responses to i.v. injections of hexamethonium were significantly greater in insulin-infused than in saline-infused rats, i.v. captopril and d(CH2)5Tyr(Me)-arginine vasopressin did not show any differences between the groups. Infusions (i.c.v.) of insulin (8 mU/10 microl) also induced cardiovascular acceleration and augmented the depressor response to i.v. hexamethonium in insulin-infused rats. The i.c.v. pretreatment with the angiotensin II antagonist losartan inhibited the pressor responses to both the i.c.v. and i.v. infusion of insulin. These results suggest that the increase in blood pressure induced by euglycemic hyperinsulinemia is elicited by sympathetic activation and that hyperinsulinemia stimulates the angiotensin system in the brain to increase sympathetic nerve activity.

Angiotensin II↗
PubMed1998

Construction of the chimeric reverse transcriptase of simian immunodeficiency virus sensitive to nonnucleoside reverse transcriptase inhibitor.

A number of structurally diverse compounds have been shown to be potent inhibitors of the DNA polymerase activity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The compounds can be grouped into two broad classes; nucleoside analogs and nonnucleoside RT inhibitors. The nonnucleoside RT inhibitors are quite specific for HIV-1 RT but not human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV) RT. We have investigated the property of SIV/HIV-1 chimeric viruses in which portions of SIV(MAC) RT were exchanged with the corresponding domain of HIV-1 RT; amino acids 176-190, 176-383 and 176-495 of HIV-1 RT. The chimeric virus, which was substituted amino acids 176-190 of RT, had detectable RT activity, and this chimeric RT was sensitive to three nonnucleoside RT inhibitors [nevirapine, HEPT derivative (E-EBU-dM) and TIBO derivative (R82913)]. To further study this chimeric virus, we purified the chimeric RT enzyme expressed in Escherichia coli and determined its kinetic properties; the Km, and Vmax values, and the Ki value of HEPT derivative calculated for the DNA polymerase activity. This study reveals that amino acids 176-190 of SIV(MAC) RT were important for the enzymatic activity and the SIV/HIV-1 chimeric RT, which had amino acids 176-190 of HIV-1, was sensitive to the nonnucleoside RT inhibitor.

Amino Acid Sequence↗
PubMed1998

S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1.

S-1153 is a new imidazole compound that inhibits human immunodeficiency virus (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse transcriptase inhibitor (NNRTI). This compound inhibits replication of HIV-1 strains that are resistant to nucleoside and nonnucleoside reverse transcriptase inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. S-1153-resistant variants are still sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication model, S-1153 and AZT administered orally showed a marked synergy for the inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph nodes, where most HIV-1 infection is thought to occur. S-1153 may be an appropriate candidate for two-to three-drug combination therapy for HIV infection.

Animals↗
PubMed1998

Inhibition in a microgravity environment of the recovery of Escherichia coli cells damaged by heavy ion beams during the NASDA ISS phase I program of NASA Shuttle/Mir mission no. 6.

We participated in a space experiment, part of the National Space Development Agency of Japan (NASDA) Phase I Space Radiation Environment Measurement Program, conducted during the National Aeronautics and Space Administration (NASA) Shuttle/Mir Mission No. 6 (S/MM-6) project. The aim of our study was to investigate the effects of microgravity on the DNA repair processes of living organisms in the in orbit. Heavy ion beam radiation- or ç-irradiation-damaged biological samples of Escherichia coli and the radioresistant bacterium Deinococcus radiodurans were prepared and placed in a biospecimen box, which was loaded into the RRMD III sensor unit of the Space Shuttle. Two identical sets of samples were left in the Spacehab's Payload Processing Facility (SPPF) in Florida, USA, as a control. (flight No. STS-84) was launched from NASA John F. Kennedy Space Center (KSC) in Florida, USA, on May 15, 1997. The mission duration was 9.22 days. An astronaut activated the biological samples in the biospecimen box in the Spacehab during orbit in order to start repair of the DNA damaged by heavy ion beams or ç-irradiation and the samples were incubated for 19 h 35 min at about 22ûC, the cabin temperature. The control specimens in the SPPF were subjected to the same treatment under terrestrial gravity. After returned to earth, we investigated cell recovery by comparing the repair of the radiation-damaged DNA of E. coli and D. radiodurans in the microgravity environment in space with that on Earth. The results indicated that the DNA repair process of E. coli, but not of D. radiodurans, cells was inhibited in a microgravity environment.

Cell Survival↗