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Biomedical subjects

K Mikami

Publications and source records attributed to K Mikami.

At least 37 records · Page 2Linked to original sources
PubMed2000

Optical rotation per refractive index unit, or enantiomeric (e) factor, for screening enantioselective catalysts through asymmetric activation or carbohydrates.

A super high-throughput screening (SHTS) system can be constructed by combining high-performance liquid chromatography (HPLC), optical rotation (OR), and refractive index unit (RIU) to determine not only the enantioselectivity of the addition of diethylzinc to an aliphatic aldehyde catalyzed by a binaphthol-zinc complex through asymmetric activation with chiral Schiff bases, but also the enantiopurity of a carbohydrate. The enantiomeric (e) factor, which we define here as optical rotation per refractive index unit, is linearly related to the percent enantiomeric excess (%ee) and is independent of concentration.

Acetonitriles↗
PubMed2000

Laparoscopic adrenalectomy for functioning adrenal tumors: clinical experiences with 38 cases and comparison with open adrenalectomy.

We reviewed 38 cases of transperitoneal or retroperitoneal laparoscopic adrenalectomy for unilateral benign functioning adrenal tumors and compared the results with those of a recent series of 36 patients undergoing an open adrenalectomy. The tumors were removed successfully in all but two cases with laparoscopy that required open laparotomy. In the other 36 cases of the laparoscopy group, mean operative time and blood loss were 225 minutes and 138 mL, respectively. Mean operative time was significantly longer for the laparoscopy group (122 minutes for open surgery: P < 0.0001), whereas mean blood loss of the laparoscopy group was almost equal to that of the open surgery group. Mean intervals to first ambulation and oral intake, and postoperative hospital stay of the laparoscopy group were significantly less than those of the open surgery group (1.4 vs 2.0 days: P = 0.014; 1.8 vs 2.9 days: P < 0.0001; and 8.5 vs 12.9 days: P < 0.0001, respectively). We conclude that laparoscopic adrenalectomy is equally effective and less invasive than open adrenalectomy. and that it should be considered as the first-choice therapy for benign adrenal tumors.

Adrenal Gland Neoplasms↗
PubMed2000

Catalytic asymmetric syntheses and biological activities of singly dehydroxylated 19-nor-1alpha,25-dihydroxyvitamin D(3) A-ring analogs in cancer cell differentiation and apoptosis.

BACKGROUND: 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) has been shown to modulate not only proliferation and differentiation, but also apoptosis in malignant cells, indicating that it could be useful for treating cancer. Little information is available concerning the structural motifs of the 1alpha, 25(OH)(2)D(3) molecule responsible for modulation of differentiation and apoptosis, however. We set out to synthesize singly dehydroxylated A-ring analogs of 19-nor-1alpha,25(OH)(2)D(3) in a catalytic asymmetric fashion, and to investigate their biological activities in leukemia HL-60 cells. RESULTS: A series of singly dehydroxylated 19-nor-1alpha,25-dihydroxyvitamin D(3) A-ring analogs were synthesized using a combinatiorial sequence of regioselective propiolate-ene reaction and catalytic asymmetric carbonyl-ene cyclization. Surprisingly, the analogs could be clearly divided into two categories; one group, bearing 1alpha-hydroxy or 3beta-hydroxy groups in the A-ring, were potent differentiators and the second group, bearing 1beta-hydroxy or 3alpha-hydroxy groups, were potent stimulators of apoptosis. CONCLUSIONS: We have clearly identified the structural motifs of 19-nor-1alpha,25(OH)(2)D(3) analogs responsible for differentiation and apoptosis in HL-60 cells. These findings will provide useful information not only for development of therapeutic agents for treatment of leukemia and other cancers, but also for structure-function studies of 1alpha,25(OH)(2)D(3).

Antineoplastic Agents↗
PubMed2000

Enantiomer-selective activation of racemic catalysts.

Asymmetric catalysts can be evolved into highly activated catalysts by association with chiral activators. This asymmetric activation process is particularly useful in racemic catalysis through selective activation of one enantiomer of the racemic catalysts. Recently, a strategy whereby a racemic catalyst is selectively deactivated by a chiral additive has been reported to yield nonracemic products. However, we have reported a strategy that is an alternative to asymmetric catalysts but is conceptually opposite, in which a chiral activator selectively activates rather than deactivates one enantiomer of a racemic chiral catalyst. The advantage of this activation strategy over the deactivation counterpart is that the activated catalyst can produce a greater enantiomeric excess (x(act)% ee) in the products than the ee attained by the enantiomerically pure catalyst on its own. Therefore, 'asymmetric activation' could provide a general and powerful strategy for the use of not only atropisomeric and, hence, racemic ligands but also chirally flexible and 'pro-atropisomeric' ligands without enantiomeric resolution!

Catalysis↗
PubMed2000

A novel Arabidopsis thaliana dynamin-like protein containing the pleckstrin homology domain.

A full-length cDNA encoding a novel type of plant dynamin-like protein, ADL3, was isolated from Arabidopsis thaliana. ADL3 is a high molecular weight GTPase whose GTP-binding domain shows a low homology to those of other plant dynamin-like proteins. ADL3 contains the pleckstrin homology domain as is in mammalian dynamins, although other plant dynamin-like proteins reported lack this domain. The ADL3 gene was expressed weakly in various tissues, except for siliques with high level expression, which is distinct from the case for other plant dynamin-like protein genes. Taken together, it is predicted that the mode of activation of ADL3 is different from those of other plant homologues.

Amino Acid Sequence↗
PubMed2000

Biological activities of 19-nor-1alpha,25-dihydroxyvitamin D3 analogs singly dehydroxylated at the C-1 or C-3 position of the A-ring.

Growing interests have been focused on the development of hybrid-analogs with modifications of the A-ring and the side chain of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3]. An exocyclic methylene group at C-10, a hydroxy group at C-1 and a hydroxy group at C-3 play a crucial role in the expression of biological activities of 1alpha,25(OH)2D3. However, relationship between the functional groups and activities has not been fully understood. We have synthesized and evaluated biological activities of several singly dehydroxylated A-ring analogs of 19-nor-1alpha,25(OH)2D3 and 19-nor-22-oxa-1alpha,25(OH)2D3. All of them have an extremely low binding affinity for vitamin D receptor (VDR). Some of them lack the 1alpha-hydroxy group that is considered to be essential for VDR-mediated gene expression, have greater or equivalent potencies to 1alpha,25(OH)2D3 for inducing differentiation and cell cycle G0-G1 arrest of human promyelocytic leukemia cells as well as for the transactivation of target genes including a rat 25-hydroxyvitamin D3-24-hydroxylase gene promoter and a human osteocalcin gene promoter in transfected mammalian cells. The assessment of a ligand/VDR/Retinoid X receptor complex formation using a two-hybrid luciferase assay revealed that the liganded VDR has high potency to form a heterodimer, but this could not explain the high biological potency of the 19-nor analogs. Other reason(s) including an interaction with transcriptional cofactors should be considered to explain the mechanism of action of 19-nor analogs.

Animals↗
PubMed2000

Dihydropyrimidine dehydrogenase activity in human pancreatic tumor tissues.

Dihydropyrimidine dehydrogenase (DPD) activity was investigated using pancreatic tumors and normal pancreatic tissues surrounding the tumors obtained from 12 patients with pancreatic cancer. The mean DPD activity (+/- SD) was 2.69 +/- 1.88 nmol/mg protein/hr in normal pancreatic tissue and was 6.59 +/- 5.36 nmol/mg protein/hr in pancreatic tumor tissues. The DPD activity in tumor tissue was two- to threefold higher (p < 0.01) than that in normal tissue, but no marked difference was observed in DPD activity among cancer stages. The DPD activity of pancreatic tumors may be a useful clinical marker of the responsibility of fluorinated pyrimidine dosing in pancreatic cancer.

Adult↗
PubMed1999

Spontaneous Enantiomeric Resolution in a Fluid Smectic Phase of a Racemate.

Right- and left-handed homochiral domains segregate in a fluid smectic phase of the racemic (R*,S*)-beta-Me-TFMHPOBC analogue shown. This CF(3)-containing liquid crystalline compound exhibits an electrooptic response in a homogeneous cell, although no macroscopic dipole is expected to exist. Moreover, the homeotropic cells of this material exhibit striped domains, which are associated with fine stripes having two opposite tilt senses with respect to the predominant stripes.

Journal Article↗
PubMed1999

Video-assisted thoracoscopic esophagomyotomy for achalasia after pulmonary lobectomy.

A 52-year-old man developed achalasia and a lung abscess due to aspiration pneumonia. We conducted a right upper lobectomy by thoracotomy for the abscess and, 2 weeks later, video-assisted thoracoscopic myotomy and fundoplication (modified Belsey Mark IV procedure) though the left thorax for achalasia. Three months after surgery, the patient was free of dysphasia and chest pain and had regained his original weight. Esophageal myotomy and fundoplication using video-assisted thoracoscopy appear to be feasible in treating achalasia involving impaired pulmonary function.

Endoscopy↗
PubMed1999

Tauroursodeoxycholic acid enhances phagocytosis of the cultured rat Kupffer cell.

BACKGROUND: Ursodeoxycholic acid is used in the treatment of acute and chronic intrahepatic cholestasis because it ameliorates cholestasis and protects hepatocytes. However, few studies have examined the effect of bile acids on the function of Kupffer cells. METHODS: The effect of various bile acids on cultured rat Kupffer cells was studied in terms of phagocytic activity in response to latex particles and morphological alterations. Video-enhanced differential interference contrast microscopy was used. RESULTS: Taurochenodeoxycholic acid and taurodeoxycholic acid reduced the number of latex particles incorporated into Kupffer cells, but taurocholic and tauroursodeoxycholic acids enhanced phagocytosis of latex particles. Inhibition of phagocytosis by taurochenodeoxycholic acid or taurodeoxycholic acid was essentially dose dependent. Tauroursodeoxycholic acid also enhanced phagocytosis by Kupffer cells in which phagocytosis had been reduced by pretreatment with taurochenodeoxycholic acid or taurodeoxycholic acid. Incorporated latex particles had a distinct translocation speed of 0.084+/-0.024 microm/s (mean maximum speed+/-SD); the speed was in the same range with tauroursodeoxycholic acid treatment. Tauroursodeoxycholic acid induced a 56% expansion of cytoplasm, associated with increased ruffling and movement of intracellular organelles. CONCLUSIONS: These observations suggest that tauroursodeoxycholic acid enhances membrane trafficking without changing translocation speed.

Animals↗
PubMed1999

Isolation of bovine serum albumin fragment P-9 and P-9-mediated fusion of small unilamellar vesicles.

Fusion peptide P-9 was isolated from bovine serum albumin by controlled pepsin degradation in the presence of caprylic acid, followed by Sephadex G-75 gel filtration and ion-exchange chromatography of CM-cellulose. By this procedure, P-9 could be strictly separated from peptic fragment P-Phe, which has a molecular weight close to that of P-9. P-Phe has no fusogenic activity. The addition of P-9 to phosphatidylcholine (PC) liposomes containing cholesterol (Chol) gave rise to an increase of absorption intensity at around pH 4.0. The increase of turbidity by P-9 addition did not decrease with increasing pH, indicating P-9-mediated fusion of PC liposomes. The extent of the fusion of PC liposomes was strongly dependent on the PC chain length and temperature. The membrane fluidity close to the polar head groups of the fatty acyl chains of PC affected markedly the extent of P-9-mediated liposome fusion. However, there was no correlation between membrane fluidity near the hydrophobic end of the fatty acyl chains and the extent of liposome fusion. The rate of liposome fusion was dependent on both lipid composition and PC chain length. These results suggest that a contact or an interaction of P-9 with liposomal membrane occurs in the rigid regions. The character of the membrane-water interface region in the liposome controls a triggering effect for P-9-mediated fusion.

Animals↗
PubMed1999

[Prognostic factors in a patients with renal cell carcinoma].

PURPOSE: The purpose of this study is to evaluate prognostic factors of renal cell carcinoma using univariate statistics. MATERIALS AND METHODS: Materials are 182 patients treated from 1976 to 1992. Kaplan-Meier method and generalized wilcoxon test were used for statistical analysis. RESULTS: Seventy cases were found incidentally without any symptoms. The overall 5- and 10-year survival rates by Kaplan-Meier method were 73.8% and 66.2%, respectively. In the univariate analysis, sex, chief complaints, tumor sizes, T-Stages, venous invasions and grades were statistically significant prognostic factors. The prognosis of males more than 60 years of age was significantly poor. The prognosis of patients with incidentalomas was far better than that of symptomatic patients. CONCLUSION: Sex and chief complaints were pointed out as significant prognostic factors for renal cell carcinoma.

Adult↗
PubMed1998

Down-regulation of epidermal growth factor receptor-signaling pathway by binding of GRP78/BiP to the receptor under glucose-starved stress conditions.

GRP78/BiP, a molecular chaperone in the endoplasmic reticulum, is induced under such adverse conditions for cell survival as glucose starvation. Induction of GRP78 has been shown to coincide with G1 cell cycle arrest, which is an important cellular defense system. In this study, we investigated involvement of GRP78 in the mechanism of growth arrest by using human epidermoid carcinoma A431 cells. Under a chemical stress condition with 2-deoxyglucose, GRP78 was induced 3-4-fold. In the stressed cells, an underglycosylated form of epidermal growth factor receptor (EGFR) was produced and the mature form was decreased. We found that the molecular chaperone GRP78 in the endoplasmic reticulum formed a stable complex with the underglycosylated EGFR but did not with the mature form. This complex formation occurred specifically under the stress conditions, and the complex was dissociated upon removal of the stress. Treatment of the GRP78-underglycosylated EGFR complex with ATP resulted in a release of the underglycosylated EGFR from GRP78, indicating that the complex could be formed through the chaperone function of GRP78. In accordance with the complex formation with endoplasmic reticulum-resident GRP78, the underglycosylated EGFR could not be translocated to the cell surface. As a result, EGF could not induce expression of cyclin D3, a G1 cyclin, in the stressed cells, whereas it did in non-stressed cells. These results indicated that, in the stressed cells, GRP78 participated in down-regulation of EGF-signaling pathway by forming a stable complex with EGFR and inhibiting EGFR translocation to the cell surface.

Carcinoma, Squamous Cell↗
PubMed1998

Asymmetric imine-ene reactions: diastereofacial selective reactions with chiral glyoxylate-derived alpha-imino esters and asymmetric catalysis of enantiofacial selective reactions with prochiral alpha-imino esters.

The diastereofacial selective "imine-ene" reactions with alpha-imino esters, prepared from (-)-8-phenylmenthyl glyoxylate, are shown to provide an efficient entry to the asymmetric synthesis of alpha-amino acids. The feasibility study of the asymmetric catalysis is also reported on the enantiofacial selective ene reactions with prochiral alpha-imino esters.

Amino Acids↗
PubMed1998

A gene encoding phosphatidylinositol-4-phosphate 5-kinase is induced by water stress and abscisic acid in Arabidopsis thaliana.

Phosphatidylinositol-4-phosphate 5-kinase (PIP5K) phosphorylates phosphatidylinositol-4-phosphate to produce phosphatidylinositol-4,5-bisphosphate as a precursor of two second messengers, inositol-1,4,5-triphosphate and diacylglycerol, and as a regulator of many cellular proteins involved in signal transduction and cytoskeletal organization. Despite PIP5K playing such an essential role in a number of physiological processes, much still remains to be made clear about its association with plants. Searching the Arabidopsis expression sequence tag database against already known yeast and mammalian PIP5K cDNAs, we identified two clones which partly encode the same Arabidopsis PIP5K and isolated a corresponding full-length cDNA encoding a protein that we designated AtPIP5K1. Recombinant AtPIP5K1 expressed in Escherichia coli possessed a PIP5K activity in vitro. Due to some structural and biochemical differences, AtPIP5K1 was not categorized as either a type I or type II PIP5K. The expression of the AtPIP5K1 mRNA was induced rapidly by treating Arabidopsis plants with drought, salt and abscisic acid, which suggests that AtPIP5K11 is involved in water-stress signal transduction. These data give evidence for a close link between phosphoinositide signaling cascades and water-stress responses in plants.

Abscisic Acid↗
PubMed1998

A mutation in Paramecium tetraurelia reveals functional and structural features of developmentally excised DNA elements.

The excision of internal eliminated sequences (IESs) from the germline micronuclear DNA occurs during the differentiation of a new macronuclear genome in ciliated protozoa. In Paramecium, IESs are generally short (28-882 bp), AT rich DNA elements that show few conserved sequence features with the exception of an inverted-terminal-repeat consensus sequence that has similarity to the ends of mariner/Tcl transposons (KLOBUTCHER and HERRICK 1995). We have isolated and analyzed a mutant cell line that cannot excise a 370-bp IESs (IES2591) from the coding region of the 51A variable surface protein gene. A single micronuclear C to T transition within the consensus sequence prevents excision. The inability to excise IES259 I has revealed a 28-bp IES inside the larger IES, suggesting that reiterative integration of these elements can occur. Together, the consensus sequence mutation and the evidence for reiterative integration support the theory that Paramecium IESs evolved from transposable elements. Unlike a previously studied Paramecium IES, the presence of this IES in the macronucleus does not completely inhibit excision of its Mild-type micronuclear copy through multiple sexual generations.

Animals↗
PubMed1998

Properties, sequence, and synthesis in Escherichia coli of 1-aminocyclopropane-1-carboxylate deaminase from Hansenula saturnus.

The plant hormone ethylene is generated from a unique precursor, 1-aminocyclopropane-1-carboxylate (ACC). In previous studies, ACC deaminase, which degrades ACC to alpha-ketobutyrate and ammonia, was found in four strains of Pseudomonas, characterized, and sequenced. To verify the wider distribution of ACC deaminase in microorganisms, we purified and sequenced ACC deaminase from the yeast Hansenula saturnus. The purified enzyme was active toward ACC, D-serine and dl-coronamic acid, indicating the same stereospecificity as the Pseudomonas enzyme, but unlike the bacterial enzyme it was not active toward beta-chloro-D-alanine and O-acetyl-D-serine. Analyses of peptides from proteolytic digests of the purified and modified ACC deaminase covered more than 90% of its amino acid sequence and showed a blocked N-terminal residue as N-acetylserine. A cDNA encoding the ACC deaminase was isolated from H. saturnus cells incubated in alpha-aminoisobutyrate medium, and sequenced. The yeast enzyme has 441 amino acid residues, of which 60 to 63% are identical to those of reported Pseudomonas enzymes. The open reading frame encoding ACC deaminase was subcloned into pET-11d and expressed in Escherichia coli BL21 (DE3) as an active enzyme.

Amino Acid Sequence↗