Biomedical subjects

T Kamei

Publications and source records attributed to T Kamei.

At least 73 records · Page 4Linked to original sources

PubMed1999

Gastric carcinoma confined to the muscularis propria: how can we detect, evaluate, and cure intermediate-stage carcinoma of the stomach?

OBJECTIVE: The most important surgical strategy for advanced gastric cancer is its detection at the curative stage. The aim of this study was to characterize the curable intermediate-stage gastric carcinomas. METHODS: Of 1120 consecutive patients who underwent gastric resection for primary gastric cancer from 1979 through 1996, 94 patients were histologically diagnosed as having cancer confined to the muscularis propria (mp cancer), analyzed clinicopathologically, and compared with patients with early and serosal cancers. RESULTS: The operative incidence of mp cancer was around 8% among cases of gastrectomy, and the ratio of mp cancer to advanced cancer began to increase in 1991. Mp cancer was at a statistically intermediate stage, between early and serosal cancers in terms of symptoms, surgical curability (96%), size and histology of the tumor, and the rate of lymph node metastasis (46%). Preoperative assessments of tumor depth were unclear using radiology and endoscopy; however, 35% of 31 cases studied were diagnosed precisely by endoscopic ultrasonography (EUS). Accuracy of lymph node metastasis diagnosis was the same (65%) by preoperative EUS and by surgeon; however, sensitivity of the surgeon's assessment was higher (69% vs 38%) and specificity of EUS was higher (83% vs 39%). The 5-yr survival rate was 85%, which was significantly better than that of serosal cancer and similar to that of early cancer. Patient outcome was not affected by lymph node metastasis or macroscopic type of tumor. CONCLUSIONS: Mp cancer should be considered an intermediate-stage cancer. Surgery with level 2 lymph node dissection should provide a cure rate similar to that for early cancer.

Aged↗

PubMed1999

Effects of the Chinese traditional medicine mao-bushi-saishin-to on therapeutic efficacy of a new benzoxazinorifamycin, KRM-1648, against Mycobacterium avium infection in mice.

The Chinese traditional medicine mao-bushi-saishin-to (MBST), which has anti-inflammatory effects and has been used to treat the common cold and nasal allergy in Japan, was examined for its effects on the therapeutic activity of a new benzoxazinorifamycin, KRM-1648 (KRM), against Mycobacterium avium complex (MAC) infection in mice. In addition, we examined the effects of MBST on the anti-MAC activity of murine peritoneal macrophages (M phi s). First, MBST significantly increased the anti-MAC therapeutic activity of KRM when given to mice in combination with KRM, although MBST alone did not exhibit such effects. Second, MBST treatment of M phi s significantly enhanced the KRM-mediated killing of MAC bacteria residing in M phi s, although MBST alone did not potentiate the M phi anti-MAC activity. MBST-treated M phi s showed decreased levels of reactive nitrogen intermediate (RNI) release, suggesting that RNIs are not decisive in the expression of the anti-MAC activity of such M phi populations. MBST partially blocked the interleukin-10 (IL-10) production of MAC-infected M phi s without affecting their transforming growth factor beta (TGF-beta)-producing activity. Reverse transcription-PCR analysis of the lung tissues of MAC-infected mice at weeks 4 and 8 after infection revealed a marked increase in the levels of tumor necrosis factor alpha, gamma interferon (IFN-gamma), IL-10, and TGF-beta mRNAs. KRM treatment of infected mice tended to decrease the levels of the test cytokine mRNAs, except that it increased TGF-beta mRNA expression at week 4. MBST treatment did not affect the levels of any cytokine mRNAs at week 8, while it down-regulated cytokine mRNA expression at week 4. At week 8, treatment of mice with a combination of KRM and MBST caused a marked decrease in the levels of the test cytokines mRNAs, especially IL-10 and IFN-gamma mRNAs, although such effects were obscure at week 4. These findings suggest that down-regulation of the expression of IL-10 and TGF-beta is related to the combined therapeutic effects of KRM and MBST against MAC infection.

Animals↗

PubMed1999

Synthesis and pharmacological evaluation of pyrroloazepine derivatives as potent antihypertensive agents with antiplatelet aggregation activity.

A series of 1-aminoalkyl-pyrrolo[2,3-c]azepin-8-one derivatives was synthesized and evaluated as alpha 1 adrenergic and serotonin 2 (5-HT2) receptor antagonists, with the aim of finding a novel antihypertensive agent potently exhibiting both activities. Some compounds with a 4-[4-(4-fluorobenzoyl)piperidino]butyl group at the 1-position exhibited both activities, and varied significantly in terms of the substituents at the 4-position of the pyrroloazepine ring. Among the compounds obtained in this study, (E)-1-[4-[4-(4-fluorobenzoyl)piperidino]-butyl]-4-hydroxyimino-7- methyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepin-8-one (15a, SUN9221) displayed potent alpha 1-adrenergic antagonistic activity (pA2 = 8.89 +/- 0.21) and 5-HT2 antagonistic activity (pA2 = 8.74 +/- 0.22) in isolated guinea pig arteries. This compound exhibited antihypertensive activity and a duration of action equivalent to orally administered prazosin or doxazosin, 3 mg/kg, in conscious spontaneously hypertensive rats, as well as potent antiplatelet aggregation activity.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1999

Age-related bone loss: relationship between age and regional bone mineral density.

We assessed the changes in regional bone mineral density according to age and examined the relationship between various regional bone mineral densities. The study was conducted in 985 Japanese women divided into < 50-years group (n = 435) and > or = 50 years group (n = 550). The total body bone mineral density and that of the head, arm, leg, thoracic (T)-spine, lumbar (L)-spine, ribs, and pelvis were measured using dual energy x-ray absorptiometry. There was a significant generalized reduction of bone mineral density in all regions after the age of 50 years. The most marked age-related decrease was observed in the L-spine. Bone mineral densities in all regions significantly correlated to each other in both age groups, but the degree of significance varied among regions. The relationship between bone mineral density of the L-spine and that of T-spine regions was the most significant in both groups. In the < 50-years group, the correlation between bone mineral density of the pelvis and that of L-spine and T-spine was the highest, followed by that between the pelvis and the leg. On the other hand, in the > or = 50-years group, the correlation between bone mineral density of the pelvis and that of the leg was the highest, but not the L-spine or T-spine. Since spine measurements are affected by vertebral deformity and/or aortic calcification, our findings suggest the pelvis may be a useful region for screening measurements of bone mineral density, especially in older women.

Absorptiometry, Photon↗

PubMed1999

Comparison between fenoterol and fenoterol plus oxitropium bromide delivered by metered-dose inhaler with InspirEase to relieve acute asthma attack.

Although the inhalation of beta2-agonists has frequently been used to relieve acute asthma attacks, the efficacy of anticholinergic agents for acute asthma attacks still remains unclear. This study was designed to compare the inhalation of fenoterol and the inhalation of fenoterol plus oxitropium bromide delivered by a metered-dose inhaler with holding chamber (InspirEase) to relieve acute asthma attacks. To accomplish this, 69 patients who had presented with an acute asthma attack were randomized to receive either fenoterol (1 puff [200 microg/puff] every 1 min for 5 min; total 1000 microg) or fenoterol plus oxitropium bromide (2 puffs [100 microg/puff] every 1 min for 5 min; total 1000 microg). The peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1) values were measured before treatment, and 1, 15, 30, and 60 min after the inhalation therapy. The ratios of improvement, PEF (or FEV1) after treatment divided by PEF (or FEV1) before treatment, were also calculated. Thirty-three patients were evaluated in the combination group and 31 patients were evaluated in the fenoterol group. The PEF value at 60 min after inhalation therapy of the fenoterol plus oxitropium bromide group (261 +/- 18 L/min, mean +/- standard error) was significantly higher compared to that of the fenoterol group (210 +/- 17 L/min). In addition, the ratios of improvement of PEF at 1, 15, 30, and 60 min after inhalation therapy were significantly higher in the fenoterol plus oxitropium bromide group compared with the fenoterol group.

Acute Disease↗

PubMed1999

[A case of cerebellar hematoma due to venous angioma presenting trigeminal dysfunction].

With regard to the natural history of venous angioma, the risk of hemorrhage is reported to be relatively higher if the lesion exists in the posterior fossa. However a recent report of 100 cases of venous angioma concluded that the risk of hemorrhage was low, being only 0.22%/year. Although the true rate of hemorrhage is uncertain, we have encountered case of cerebellar hematoma due to venous angioma in the posterior fossa where the patient presented with trigeminal dysfunction and cerebellar ataxia, without any history of hypertension. We considered that venous angioma in the posterior fossa might cause cerebellar hemorrhage. After removal of the hematoma, the patient's symptoms were resolved. In the posterior fossa, a relatively higher volume of venous blood would cause venous congestion to occur more easily, leading to damage of the fragile wall of the angioma.

Cerebellar Ataxia↗

PubMed1999

Pharmacological properties of J-104132 (L-753,037), a potent, orally active, mixed ETA/ETB endothelin receptor antagonist.

J-104132 [(+)-(5S,6R, 7R)-2-butyl-7-[2-((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3, 4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine-6-carboxylic; also referred to as L-753,037] is a potent, selective inhibitor of ETA and ETB endothelin (ET) receptors (e.g., Ki: cloned human ETA = 0.034 nM; cloned human ETB = 0.104 nM). In both ligand-binding and isolated tissue preparation protocols, the inhibition of ET receptors with J-104132 is reversible and competitive. In vitro, J-104132 is a potent antagonist of ET-1-induced accumulation of [3H]inositol phosphates in Chinese hamster ovary cells stably expressing cloned human ETA receptors (IC50 = 0.059 nM), ET-1-induced contractions in rabbit iliac artery (pA2 = 9.70) and of BQ-3020-induced contractions in pulmonary artery (pA2 = 10.14). J-104132 is selective for ET receptors because it had no effect on contractions elicited by norepinephrine or KCl in the vascular preparations. The in vivo potency of J-104132 was assessed using challenges with exogenous ET-1. In conscious mice, 5 nmol/kg i.v. ET-1 causes death. Pretreatment with J-104132 prevents the lethal response to ET-1 when administered i.v. (ED50 = 0.045 mg/kg) or p.o. in fed animals (ED50 = 0.35 mg/kg). In conscious, normotensive rats, pressor responses to 0.5 nmol/kg i.v. ET-1 are inhibited by J-104132 after i.v. (0.1 mg/kg) or p.o. (1 mg/kg) administration. In anesthetized dogs, ET-1 was administered directly into the renal artery or brachial artery to generate dose-response (blood flow) curves, and the inhibitory potency of J-104132 (i.v. infusion) was quantified. J-104132 produced greater than 10-fold shifts in the ET-1 dose-response curves at 0.03 mg/kg/h (renal) and 0.3 mg/kg/h (brachial). Oral bioavailability of J-104132 in rats was approximately 40%. These studies indicate that J-104132 is a selective, potent, orally active antagonist of both ETA and ETB receptors and is an excellent pharmacological tool to explore the therapeutic use of a mixed ETA/ETB receptor antagonist.

Animals↗

PubMed1999

[Differential diagnosis among reactive mesothelia, adenocarcinoma and malignant mesothelioma].

We tried to distinguish reactive mesothelia (RM), adenocarcinoma (AC), and malignant mesothelioma (MM) in the body fluid. Morphometrically, nuclear uneveness index (NUI) of the benign and neoplastic mesothelial cells was smaller than that of the adenocarcinoma cells. About N/C area ratio, that of reactive mesothelial cells was larger than that of two types of malignant cells (lung AC and MM). But that of gastric AC was the largest in all groups. Ultrastructurally, length to diameter ratio (LDR) of mesothelioma cells was statistically greater, and intermediate filaments of benign and malignant mesothelial cells were more abundant than that of AC. For immunohistochemical diagnosis, it was necessary to use appropriately the specific and sensitive markers for benign and malignant mesothelial cells, or AC cells in combination.

Adenocarcinoma↗

PubMed1999

[Mechanisms of cell adhesion and migration].

In order to understand the molecular mechanisms underlying cancer metastasis, it is important to clarify the mechanisms of cell adhesion and cell migration. When epithelial cells start to migrate, cell-cell junctions are first disrupted. During migration, membrane protrusions, such as lamellipodia and filopodia, are observed externally at the cell front, and retraction at the cell rear. In addition, dynamic reorganization of the actin cytoskeleton, such as disassembly and reassembly of stress fibers at cell-cell and cell-matrix junctions and membrane protrusions, is observed internally. Our experiments have demonstrated that the Rho and Rab family small G proteins coordinately regulate cell adhesion and migration of cultured MDCK cells. The Rho family consists of the Rho, Rac, and Cdc 42 subfamilies. The Rho subfamily regulates stress fiber formation, and integrin-based cell matrix adhesion. Furthermore, the Rac and Cdc 42 subfamilies regulate lamellipodia and filopodia formation, respectively, as well as cadherin-based cell-cell adhesion. The detailed modes of action of these small G proteins remain to be clarified; however, it is known that these proteins regulate cell adhesion and migration through reorganization of the actin cytoskeleton. The Rab family has over thirty members. We have found that some Rab family members are involved in HGF- or phorbol ester-induced endocytosis and exocytosis (recycling) of adhesion molecules such as integrin and cadherin. Endocytosis and exocytosis of these adhesion molecules are accompanied by disassembly and reassembly of the actin cytoskeleton, respectively, in a well coordinated manner. Thus, we propose the cooperative roles of the Rho and Rab families in cell adhesion and migration.

Animals↗

PubMed1999

Prediction of vertigo recurrences in Meniere's disease by the head-shaking test.

Researchers have observed that when head-shaking nystagmus (HSN) is provoked in patients with peripheral vestibular disorders, usually (in more than 75% of cases) it beats toward the normal or unaffected ear. The reverse of this pattern occurs commonly in patients with Meniere's disease. This finding presumably reflects the changeable pathophysiological state of the labyrinth of Meniere's disease. We retrospectively analyzed clinical records of eight patients who had unilateral Meniere's disease and came to Gunma University Hospital for consultation in the period from 1984 through 1989. All patients satisfied the following condition: In the period prior to the attacks of vertigo, for which a 10-day period preceding the attack was arbitrarily considered (the forerunning period), HSN reversed its direction, appeared, or disappeared. When HSN showed a biphasic pattern, only the first phase was considered in this present analysis. In the period before the attack, HSN reversed its direction from the normal to the morbid ear five times in four patients, appeared toward the morbid ear in three patients, and disappeared from one beating toward the normal ear before the forerunning period of vertigo attacks in one patient. These findings suggest that the occurrence of HSN directed to the morbid ear in the recuperation period in Meniere's disease might indicate the impending recurrence of a vertigo attack in a few days. In the present group of patients, vertigo attacks occurred from 6 hours to 8 days (average, 3.2 days) after the observation of HSN beating toward the morbid ear. In three of these patients, the immediate administration of isosorbide (a hyperosmotic diuretic) in this stage successfully suppressed the recurrence of vertigo attacks.

Adult↗

PubMed1999

In vivo metabolism of a new anticancer agent, 6-N-formylamino-12, 13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosil)5H-indolo [2,3-a]pyrrolo [3,4-c]carbazole-5,7(6H)-dione (NB-506) in rats and dogs: pharmacokinetics, isolation, identification, and quantification of metabolites.

6-N-formylamino-12,13-dihydro-1, 11-dihydroxy-13-(beta-D-glucopyranosil)5H-indolo [2,3-a]pyrrolo [3, 4-c]carbazole-5,7(6H)-dione (NB-506), a potent inhibitor of DNA topoisomerase I, is currently under development for the treatment of cancer. We investigated the pharmacokinetics of NB-506 after i.v. administration in rats and dogs. The plasma concentration of NB-506 decreased biexponentially in rats and dogs with terminal half-lives of approximately 2 h. The area under the curve increased nonlinearly with increasing dose in rats. In contrast, there was a linear relationship between the area under the curve and the dose in dogs. In rats, the plasma clearance decreased with increasing dose up to 187.5 mg/m2 but remained virtually unchanged at the highest dose. The Vdss of NB-506 in rats and dogs was much greater than the plasma volume, indicating that NB-506 is highly distributed to tissue from plasma in these animals. There were marked species differences in the plasma concentrations of ED-501 after i.v. administration of NB-506 to rats and dogs. To better understand the mechanisms of nonlinear pharmacokinetics in rats, in vivo metabolites were determined. After i.v. administration of [14C]NB-506 to rats, two unknown metabolites (RBM-1 and RBM-2), deformyl metabolite (ED-501), and unchanged drug (NB-506) were identified. Mass and NMR spectra analysis revealed that RBM-1 is an 11-O-glucuronide of NB-506 (ED-594) and that RBM-2 is an 11-O-glucuronide of ED-501 (ED-595). In this study, the pharmacokinetics of NB-506 was demonstrated to be nonlinear in rats, probably because of saturation of the enzyme systems catalyzing the deformylation and glucuronidation of NB-506 in rats.

Animals↗

PubMed1999

In vitro metabolism of a new anticancer agent, 6-N-formylamino-12, 13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosil)5H-indolo+ ++[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione (NB-506), in mice, rats, dogs, and humans.

The metabolism of 6-N-formylamino-12,13-dihydro-1, 11-dihydroxy-13-(beta-D-glucopyranosil)5H-indolo [2,3-a]pyrrolo [3, 4-c]carbazole-5,7(6H)-dione (NB-506), a potent inhibitor of DNA topoisomerase I, was characterized in mice, rats, dogs, and humans in vitro. NB-506 was deformylated to ED-501 in mouse and rat plasma with enzyme activity of 140 and 116 pmol/min/mg protein, respectively. The enzyme activity in dog and human plasma was found to be less than 1.7 pmol/min/mg protein. In liver S9 and small intestine S9 samples from mice and rats, activity of the enzyme was very low. Also, there was no activity in the liver or small intestine of dogs and humans. The enzyme involved in the conversion of NB-506 to ED-501 in rat plasma is a rodent-specific serine enzyme with a molecular mass of 138KDa. The Vmax and Km values were 6.3 nmol/min/ml plasma and 54 microM at an optimum pH of 7.4, respectively. Although NB-506 was converted to ED-551 in dog and human plasma in vitro, no conversion was observed in mouse and rat plasma. In human plasma this conversion was not affected by heat treatment (100 degreesC for 1 min), but was inhibited completely by 50 mM EDTA, indicating that the reaction is a chemical reaction catalyzed by metal ions. Although NB-506 was not metabolized by cytochrome P-450 isozymes in liver, this drug was glucuronized in mice, rats, and humans, but not in dogs. These results suggest that a species difference in the metabolism of NB-506 occurred in the liver as well as in plasma. There appeared to be species differences in the metabolism of NB-506 in vitro, correlating well with the species-dependent pharmacokinetics of this drug in vivo.

Animals↗

PubMed1998

Shs1p: a novel member of septin that interacts with spa2p, involved in polarized growth in saccharomyces cerevisiae.

The Rho family small G proteins regulate various cell functions including cytokinesis. We have shown that Bni1p, a potential target of Rho1p, interacts with Spa2p and that Spa2p is required for the localization of Bni1p at the growth sites in Saccharomyces cerevisiae. We isolated here a novel member of the septin family, implicated in cytokinesis, as a Spa2p-binding protein by the yeast two-hybrid method. We named this gene SHS1 (Seventh Homolog of Septin). The shs1 mutant cells showed cytokinesis deficiency and Shs1p was localized at the bud neck in budded cells. The Spa2p-Shs1p interactions may play an important role in cytokinesis.

Cell Cycle Proteins↗

PubMed1998

Interaction of Bnr1p with a novel Src homology 3 domain-containing Hof1p. Implication in cytokinesis in Saccharomyces cerevisiae.

Proteins containing the formin homology (FH) domains FH1 and FH2 are involved in cytokinesis or establishment of cell polarity in a variety of organisms. We have shown that the FH proteins Bni1p and Bnr1p are potential targets of the Rho family small GTP-binding proteins and bind to an actin-binding protein, profilin, at their proline-rich FH1 domains to regulate reorganization of the actin cytoskeleton in the yeast Saccharomyces cerevisiae. We found here that a novel Src homology 3 (SH3) domain-containing protein, encoded by YMR032w, interacted with Bnr1p in a GTP-Rho4p-dependent manner through the FH1 domain of Bnr1p and the SH3 domain of Ymr032wp. Ymr032wp weakly bound to Bni1p. Ymr032wp was homologous to cdc15p, which is involved in cytokinesis in Schizosaccharomyces pombe, and we named this gene HOF1 (homolog of cdc 15). Both Bnr1p and Hof1p were localized at the bud neck, and both the bnr1 and hof1 mutations showed synthetic lethal interactions with the bni1 mutation. The hof1 mutant cells showed phenotypes similar to those of the septin mutants, indicating that HOF1 is involved in cytokinesis. These results indicate that Bnr1p directly interacts with Hof1p as well as with profilin to regulate cytoskeletal functions in S. cerevisiae.

Actins↗

PubMed1998

Differential regulation of lipopolysaccharide (LPS) activation pathways in mouse macrophages by LPS-binding proteins.

LPS binding to its receptor(s) on macrophages induces the synthesis of inflammatory mediators involved in septic shock. While the signaling mechanism(s) remains to be fully defined, the human LPS-binding protein (LBP) is known to regulate responses to LPS by facilitating its binding to CD14 on human monocytes. The structurally related bactericidal permeability increasing protein (BPI) differs from LBP by inhibiting LPS-induced human monocyte activation. We have demonstrated that, unlike the human monocyte response to LPS, both LBP and BPI inhibited LPS-stimulated TNF-alpha production in mouse peritoneal macrophages. In contrast, LPS-dependent nitric oxide release was not affected by LBP. LPS induces the phosphorylation of a number of proteins in a dose and time-dependent manner, however, the pattern of LPS-induced phosphorylation was not reduced by either LBP or BPI under conditions that result in selective TNF-alpha inhibition. Further, activation of the transcription factor NF-kappaB in response to LPS was also not modified by either LBP or BPI. Finally, no differences were detected in TNF-alpha or inducible nitric oxide synthase mRNA accumulations induced by LPS in the presence or absence of either protein, whereas a slight decreased mRNA stability was observed in the group with LPS treatment. These results would suggest that many of the early signaling events contribute to LPS-induced macrophage signaling at a point preceding the divergence of pathways that differentially regulate TNF-alpha and NO production.

Acute-Phase Proteins↗

PubMed1998

Determination of montelukast sodium in human plasma by column-switching high-performance liquid chromatography with fluorescence detection.

MK-0476 (montelukast sodium) is a potent and selective cysteinyl leukotriene receptor antagonist that is being investigated in the treatment of asthma. A simple and sensitive method for the determination of MK-0476 in human plasma was developed using column-switching high-performance liquid chromatography (HPLC) with fluorescence detection. A plasma sample was injected directly onto the HPLC system consisting of a pre-column (Capcell pak MF) and an analytical column (Capcell pak C18) which were connected with a six-port switching valve. The column eluate was monitored with a fluorescence detector (excitation at 350 nm; emission at 400 nm). The calibration curve was linear in a concentration range of 1-500 ng ml(-1) for MK-0476 in human plasma. The intra-day coefficients of variation of all concentrations within the range was less than 9.2%, and the intra-day accuracy values were between 97.2 and 114.6%. This method was used to measure the plasma concentration of MK-0476 following oral administration of the drug in humans.

Acetates↗

PubMed1998

Cholesterol lowering in low density lipoprotein receptor knockout mice overexpressing apolipoprotein E.

Apo E is a key molecule in the lipoprotein metabolism; thus, genetic manipulation of apo E may prove useful in the treatment of hypercholesterolemia. To test the feasibility of this idea, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpress the rat apo E transgene (ETg+/+:LDLRKO), and compared their plasma lipoprotein profiles with those of nonexpressing LDLR knockout mice (ETg-/-:LDLRKO). On a normal chow diet, the mean plasma cholesterol level of ETg+/+:LDLRKO mice was significantly lower than that of ETg-/-:LDLRKO mice (189 versus 240 mg/dl, P < 0. 01). The LDL fraction was selectively reduced in the ETg+/+:LDLRKO mice. Despite the challenge with an atherogenic diet, cholesterol lowering was persistently observed and fatty streak lesions in the aortic sinus were significantly suppressed in the mice overexpressing apo E. These results imply that stimulation of hepatic production of apo E may be used as a promising adjunctive therapy for homozygous familial hypercholesterolemia.

Animals↗

PubMed1998

Interaction of Rho1p target Bni1p with F-actin-binding elongation factor 1alpha: implication in Rho1p-regulated reorganization of the actin cytoskeleton in Saccharomyces cerevisiae.

The RHO1 gene encodes a homolog of mammalian RhoA small G protein in the yeast Saccharomyces cerevisiae. We have shown that Bni1p is one of the downstream targets of Rho1p and regulates reorganization of the actin cytoskeleton through the interaction with profilin, an actin monomer-binding protein. A Bni1p-binding protein was affinity purified from the yeast cytosol fraction and was identified to be Tef1p/Tef2p, translation elongation factor 1alpha (EF1alpha). EF1alpha is an essential component of the protein synthetic machinery and also possesses the actin filament (F-actin)-binding and -bundling activities. EF1alpha bound to the 186 amino acids region of Bni1p, located between the FH1 domain, the proline-rich profilin-binding domain, and the FH2 domain, of which function is not known. The binding of Bni1p to EF1alpha inhibited its F-actin-binding and -bundling activities. The BNI1 gene deleted in the EF1alpha-binding region did not suppress the bni1 bnr1 mutation in which the actin organization was impaired. These results suggest that the Rho1p-Bni1p system regulates reorganization of the actin cytoskeleton through the interaction with both EF1alpha and profilin.

Actins↗