Biomedical subjects

T Yamazaki

Publications and source records attributed to T Yamazaki.

At least 73 records · Page 4Linked to original sources

PubMed2001

Catheter-tip fixation of a percutaneously implanted port-catheter system to prevent dislocation.

The aim of this study was to evaluate the incidence of catheter tip dislocation in patients with percutaneously implanted port-catheters for hepatic arterial chemotherapy with catheter tip fixation. Forty-seven patients (31 men and 16 women; mean age 66 years) with unresectable advanced liver cancers (primary liver cancer, n=19; metastatic liver cancer, n=28) underwent percutaneously implantable port-catheter system placement with the tip fixed at the gastroduodenal artery with coils and side hole opened at the common hepatic artery. In 39 patients, n-butyl cyanoacrylate (NBCA) mixed with Lipiodol was added for fixation. The position of the side hole after the indwelling port-catheter system was investigated, and the correction method in cases with catheter dislocation was determined. In 2 (25%) of the 8 patients without NBCA fixation, dislocation of the catheter was noted, in contrast to none (0%) of 37 patients with NBCA fixation. Two patients in whom NBCA was used could not undergo long-term intra-arterial chemotherapy because of hepatic arterial thrombotic occlusion which occurred after placement of the indwelling catheter, and were excluded from the evaluation. Fixation of the catheter tip with combined use of coils and NBCA--Lipiodol mixture to the gastroduodenal artery is important to prevent dislocation of the port-catheter system.

Aged↗

PubMed2001

Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 2.

Highly potent 1,3-beta-D-glucan synthase inhibitors, 7b, 10a, 10b and 12, have been identified by the chemical modification of the ornithine residue of a fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. These compounds showed stronger antifungal activity against systemic candidiasis as well as pulmonary aspergillosis in mice, and less hepatotoxicity as compared with 1.

Animals↗

PubMed2001

Mitochondrial DNA alteration in esophageal cancer.

It has been reported that various cancers frequently have mutations in the D-loop region of mitochondrial DNA (mtDNA). We examined the genetic alterations in this region of esophageal cancer using direct sequencing. Of 68 sequence variants, 15 have not been reported to date. Tumor mtDNA with these variants were compared with mtDNA from corresponding normal esophageal mucosa. Two of 37 primary esophageal cancers (5%) contained somatic mutations in the D-loop region of mtDNA. Although the mutation rate of mitochondrial tumor DNA within the D-loop was not high, this result suggested that mtDNA mutations play a role in the development of esophageal cancer.

DNA Mutational Analysis↗

PubMed2001

Stable operation of a 300-m laser interferometer with sufficient sensitivity to detect gravitational-wave events within our galaxy.

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of h approximately 5x10(-21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.

Astronomy↗

PubMed2001

Furan ring oxidation strategy for the synthesis of macrosphelides A and B.

By using the convenient protocol for conversion of 2-substituted furans into 4-oxo-2-alkenoic acids ((i) NBS, (ii) NaClO(2)), macrosphelide B (2) was synthesized from furyl alcohol 5 (>98% ee) and acid 6 (99% ee). The protocol was first applied to the PMB ether of 5 to afford acid 13b. On the other hand, DCC condensation of acid 6 with 5 gave 16 after deprotection of the TBS group. Condensation was again carried out between 13b and 16 to furnish the key ketone 17, which upon reduction with Zn(BH(4))(2) afforded anti alcohol 18 stereoselectively (15:1). After protection/deprotection steps, the furan 18 was converted to seco acid 3 by using the furan oxidation protocol mentioned above, and lactonization of 3 with Cl(3)C(6)H(2)COCl, Et(3)N, and DMAP afforded 22 (MOM ether of 2), which upon deprotection with TFA produced 2. Transformation of 22 to macrosphelide A (1) was then investigated. Although the chelation-controlled reduction of 22 should afford the desired anti alcohol 24, Zn(BH(4))(2) at <-90 degrees C gave a 2 approximately 1:1 mixture of anti/syn alcohols. On the contrary, reduction with NaBH(4) in MeOH at -15 degrees C produced the syn isomer 23 with >10:1 diastereoselectivity. Mitsunobu inversion of the resulting C(14)-hydroxyl group and deprotection of the MOM group with TFA afforded 1. Similarly, reduction of 2 with NaBH(4) afforded the C(14)-epimer of 1 stereoselectively. The observed stereoselectivity in the reductions of 22 and 2 could be explained on the basis of computer-assisted calculation, which showed presence of the low-energy conformers responsible for the stereoselective reduction. In addition, conversion of 2 to 1 was established, for the first time.

Furans↗

PubMed2001

Mesyloxy-group migration as the stereoselective preparation method of various functionalized olefins and its reaction mechanism.

[structure: see text]. It was demonstrated that mesylation of appropriate gamma,gamma-difluorinated allylic alcohols under usual conditions furnished the corresponding alpha,alpha-difluorinated allylic mesylates, possibly by way of 1,3-mesyloxy-group migration after formation of the expected "normal" intermediates, gamma,gamma-difluorinated allylic mesylates. This rearrangement was conveniently applied to the construction of trisubstituted allylic alcohols, alpha,beta-unsaturated esters, amides, or ketones in good to excellent chemical yields with exclusive E selectivities.

Journal Article↗

PubMed2001

Identification of the cobalamin-dependent methionine synthase gene, metH, in Vibrio fischeri ATCC 7744 by sequencing using genomic DNA as a template.

To confirm the presence of cobalamin-dependent methionine synthase (CDMS) in luminous bacteria, which is a prerequisite for the substantiation of our proposals on the physiological function of the lux operon, we identified the CDMS gene (metH) in Vibrio fischeri ATCC 7744. Two partial metH sequences, one located near the 5'-terminus of the gene and the other near the 3'-terminus, were sequenced by a PCR based method. To design a new set of PCR primers located on the two flanking regions of the gene, the genomic DNA was sequenced by SUGDAT method (sequencing using genomic DNA as a template) upstream or downstream from the respective partial gene sequences. Subsequently a 4.2 kb DNA fragment containing the whole metH was amplified by PCR and sequenced. The number of amino acid residues comprising the protein (1226 amino acids) was comparable to those of known CDMSs. The deduced amino acid sequence showed 85, 74, 55, 31, 30, 52, or 52% identity with that of Vibrio cholerae, Escherichia coli, Deinococcus radiodurans, Synechocystis PCC6803, Mycobacterium tuberculosis, Caenorhabditis elegans or Homo sapiens, respectively. All the predicted amino acid residues for the binding of cobalamin and S-adenosylmethionine were conserved. In the regulatory region of the V. fischeri metH, the binding site of the met repressor, MetJ, was present, although the site is atypically not present in E. coli metH or Salmonella typhimurium metH. It was shown that nucleotide sequences, even long ones, can be determined without a cloning step, if only parts of the DNA fragment to be sequenced are amplified by PCR.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2001

Interaction of the C-terminal domain of the E. coli RNA polymerase alpha subunit with the UP element: recognizing the backbone structure in the minor groove surface.

The C-terminal domain of the alpha-subunit of Escherichia coli RNA polymerase (alphaCTD) is responsible for transcriptional activation through interaction with both activator proteins and UP element DNA. Previously, we determined the solution structure of alphaCTD. Here, we investigated the interaction between alphaCTD and UP element DNA by NMR. DNA titration curves and intermolecular NOE measurements indicate that alphaCTD can bind to multiple sites on the UP element DNA. Unlike many transcription factors, alphaCTD does not have a strict base sequence requirement for binding. There is a good correlation between the strength of the interaction and the extent of intrinsic bending of the DNA oligomer estimated from the gel retardation assay. We propose that alphaCTD recognizes the backbone structure of DNA oligomers responsible for the intrinsic bending. Moreover, NMR studies and drug competition experiments indicated that alphaCTD interacts with the UP element on the minor groove side of the DNA. The C-terminal end of helix-1, the N-terminal end of helix-4, and the loop between helices 3 and 4 are used for the interaction. Based on these observations, we propose a model for the UP element-alphaCTD complex.

Base Sequence↗

PubMed2001

Effects of spinorphin and tynorphin on synaptic transmission in rat hippocampal slices.

Spinorphin has been isolated from the bovine spinal cord as an endogenous inhibitor of enkephalin-degrading enzymes (aminopeptidase, dipeptidyl aminopeptidase III, angiotensin-converting enzyme and enkephalinase), and tynorphin has been synthesized as a more potent inhibitor of dipeptidyl aminopeptidase III. In this study, the effects of spinorphin and tynorphin on synaptic transmission were studied in rat isolated hippocampal slices. Field potentials were recorded from the CA1 region after stimulation of Schaffer collaterals. Spinorphin (1 microM), which alone had no effect, potentiated the facilitatory effects of enkephalin on the filed potentials at a stimulation interval of 15 s. At a stimulation interval of 10--4 s, spinorphin alone frequency dependently inhibited the field potential. On the other hand, tynorphin (1 microM), which alone had no effect at any stimulus interval, tended to potentiate the facilitatory effects of enkephalin. Spinorphin blocked long-term potentiation induced by tetanic stimulation (100 Hz, 1 s), whereas tynorphin had no effect on long-term potentiation. These results suggest that, at a low stimulation frequency, spinorphin potentiates the facilitatory effects of enkephalin by preventing degradation of enkephalin, whereas at a high stimulation frequency spinorphin use dependently inhibits synaptic transmission independently of enkephalin. On the other hand, tynorphin tends to potentiate the facilitatory effects of enkephalin without use-dependent inhibition.

Animals↗

PubMed2001

Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 1.

Highly potent 1,3-beta-D-glucan synthase inhibitors 10, 11 and 13 have been identified by the chemical modification of the fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. D-Ornithine derivative (10) showed improved antifungal activity in the systemic candidiasis model in mice and reduced hepatotoxicity in vitro, as compared with 1.

Animals↗

PubMed2001

Effects of lysozyme and bovine serum albumin on membrane characteristics of dipalmitoylphosphatidylglycerol liposomes.

The effects of adsorption of two kinds of proteins on the membrane characteristics of liposomes were examined at pH 7.4 in terms of adsorption amounts of proteins on liposomes, penetrations of proteins into liposomal bilayer membranes, phase transition temperature, microviscosity and permeability of liposomal bilayer membranes, using positively charged lysozyme (LSZ) and negatively charged bovine serum albumin (BSA) as proteins and negatively charged L-alpha-dipalmitoylphosphatidylglycerol (DPPG) liposomes. The saturated adsorption amount of LSZ was 720 g per mol of liposomal DPPG, while that of BSA was 44 g per mol of liposomal DPPG. The penetration of LSZ into DPPG lipid membranes was greater than that of BSA. The microviscosity in the hydrophobic region of liposomal bilayer membranes increased due to adsorption (penetration) of LSZ or BSA, while the permeability of liposomal bilayer membranes increased. The gel-liquid crystalline phase transition temperature of liposomal bilayer membranes was not affected by adsorption of LSZ or BSA, while the DSC peak area (heat of phase transition) decreased with increasing adsorption amount of LSZ or BSA. It is suggested that boundary DPPG makes no contribution to the phase transition and that boundary DPPG and bulk DPPG are in the phase-separated state, thereby increasing the permeability of liposomal bilayer membranes through adsorption of LSZ or BSA. A possible schematic model for the adsorption of LSZ or BSA on DPPG liposomes was proposed.

Journal Article↗

PubMed2001

The rate-determining step in P450 C21-catalyzing reactions in a membrane-reconstituted system.

Adrenal cytochrome P450 C21 in a membrane-reconstituted system catalyzed 21-hydroxylation of 17alpha-hydroxyprogesterone at a rate higher than that for progesterone in the steady state at 37 degrees C. The rate of product formation in the steady state increased with the concentration of the complex between P450 C21 and the reductase in the membranes. The complex formation was independent of the volume of the reaction, showing that the effective concentrations of the membrane proteins should be defined with the volume of the lipid phase. The rates of conversion of progesterone and 17alpha-hydroxyprogesterone to the product in a single cycle of the P450 C21 reaction were measured with a reaction rapid quenching device. The first-order rate constant for the conversion of progesterone by P450 C21 was 4.3 +/- 0.7 s(-)1, and that for 17alpha-hydroxyprogesterone was 1.8 +/- 0.5 s(-)1 at 37 degrees C. It was found from the analysis of kinetic data that the rate-determining step in 21-hydroxylation of progesterone in the steady state was the dissociation of product from P450 C21, whereas the conversion to deoxycortisol was the rate-determining step in the reaction of 17alpha-hydroxyprogesterone. The difference in the rate-determining steps in the reactions for the two substrates was clearly demonstrated in the pre-steady-state kinetics.

17-alpha-Hydroxyprogesterone↗

PubMed2001

Application of hypothermia to autologous stem cell purging.

Autologous stem cell transplantation is used widely after high-dose chemotherapy for treating hematological and other malignancies. Bone marrow harvested for autologous bone marrow transplantation may contain residual malignant cells even when the cancer is judged to be in remission. Attempts to purge marrow of its putative residual malignant cells may delay hemopoietic reconstitution and are of uncertain efficacy. In this report, we demonstrate the possibility of applying hypothermia to autologous stem cell purging. Using clonogenic assay, we compared the surviving fraction of human leukemia (HL60, K562) and human small cell lung cancer (H69) cell lines with that of normal human bone marrow CFU-GM and BFU-E cells after incubation at 4 +/- 0.1 degrees C for 24 and 48 h. Hypothermia decreased the surviving fraction of HL60, H69, and K562 cells. In contrast, the surviving fractions of stem cells were not affected by the temperature shift. The surviving fraction of HL60 cells at 4 degrees C cooling was significantly lower than that at 22 degrees C cooling. These findings suggest that in vitro hypothermia may selectively purge residual malignant cells in stored remission bone marrow and may be applicable before autologous bone marrow transplantation. In addition, the method is very simple and cost effective.

Bone Marrow Purging↗

PubMed2001

Neutrophil cytoskeletal disease.

Neutrophils and other phagocytes migrate to the site of infection, ingest pathogens, and destroy them after releasing granule contents and active oxygen. These activities of the cells are closely associated with a rapid reorganization of the cytoskeleton, in which actin polymerizes, cross-links, anchors to the membrane and depolymerizes under the control of various actin-associated proteins. Defect in actin or its associated proteins results in neutrophil cytoskeletal disease where abnormality primarily appears as motility or chemotactic defect of the cells. Although their molecular mechanisms have not been elucidated, neutrophil actin dysfunction and neutrophil actin dysfunction with abnormal 47- and 89-kd proteins have been reported. Recently, abnormal-beta-actin disease and disease with Rac 2 mutation, both of which accompany neutrophil chemotactic dysfunction, were analyzed at the molecular level. These diseases are systemic, but neutrophil dysfunction of the patients is remarkable. Here we review the literature on diseases due to cytoskeletal abnormality. Many other diseases with actin or actin-associated protein dysfunction may be reported in the near future.

Actins↗

PubMed2001

Pancreatectomy combined with superior mesenteric-portal vein resection for adenocarcinoma in pancreas.

The aims of this study were to investigate morbidity, mortality, and survival of patients with ductal adenocarcinoma of the pancreas who underwent pancreatectomy without (group 1) or with (group 2) en bloc portal vein resection and to study the degree of carcinoma invasion of the portal vein in group 2. The medical records of 46 and 28 patients in groups 1 and 2, respectively, were reviewed. In addition, the degree of invasion of the wall of the portal vein was categorized histologically into three types: type I, transmural invasion involving the intima; type II, invasion of the wall of the vein without intimal involvement; and type III, compression of the wall of the vein by surrounding carcinoma without true invasion. The morbidity and mortality in group 1 (26% and 4%) were not different from those in group 2 (32% and 4%). Similarly, there was no difference in survival between the two groups. Survival tended to vary directly with the depth of invasion of the wall of the portal vein: type I 6.8 +/- 1.9 months; type II 15.3 +/- 6.4 months; type III 20.6 +/- 13.0 months. These findings suggest that en bloc resection of the pancreas and the portal vein does not increase mortality and morbidity after pancreatectomy; survival after en bloc resection was similar to that of patients not requiring portal vein resection. Combined resection of the pancreas with the portal vein could be an option in the treatment of pancreatic cancer with direct invasion of the portal vein.

Adenocarcinoma↗

PubMed2001

Preliminary study of fortnightly irinotecan hydrochloride plus cisplatin therapy in patients with advanced gastric and colorectal cancer.

PURPOSE: Irinotecan hydrochloride shows a strong activity against gastric cancer and colorectal cancer, while combined therapy with irinotecan and cisplatin is useful for gastric cancer. However, myelosuppression and diarrhea are still dose-limiting factors. To reduce such toxicities to enable therapy to be performed on an outpatient basis, we tested the effect of divided administration of cisplatin. METHODS: Irinotecan (60 mg/m2) plus cisplatin (30 mg/m2) were administered on days 1 and 15 every 4 weeks to 13 patients with advanced gastric cancer and 13 with advanced colorectal cancer. Treatment was continued if a leukocyte count > or = 3000/mm3, a platelet count > or = 100,000/mm3, and grade 0 diarrhea were confirmed. Doses were reduced if grade 3-4 hematological toxicity and grade 2 or higher nonhematological toxicity occurred. RESULTS: The major toxicity was leukopenia (neutropenia), but grade 3-4 nonhematological toxicity was not observed. The response rate was 41.7% for gastric cancer (5/12 evaluable patients) and 36.7% for colorectal cancer (4/11 evaluable patients). The median survival time was 313 days (range 29-920 days) for gastric cancer patients and 490 days (range 83-1184 + days) for colorectal cancer patients. CONCLUSION: Fortnightly administration of irinotecan and cisplatin (with a divided cisplatin dose) seems to be a useful regimen for gastrointestinal cancer. It reduces toxicity while maintaining a good antitumor effect.

Adult↗

PubMed2001

Strict closed-system drainage for treating chronic subdural haematoma.

A comparative study chiefly of the recurrence rate of chronic subdural haematoma after two treatment modalities was conducted. Patients were divided into a burr hole strict closed-system drainage group (SCD group; n=56) and a burr hole closed-system drainage with irrigation group (CDI group; n=45). The burr hole strict closed-system drainage involved simply inserting a drainage tube into the haematoma cavity as quickly as possible after minimally incising the haematoma capsule. The introduction of air into the haematoma cavity was prevented, and irrigation was not performed. Symptoms in both groups disappeared soon after surgery, with no postoperative complications. Haematoma recurred in one patient (1.8%) of the SCD group compared with 5 (11.1%) of the CDI group. The rate of recurrence was significantly lower for the SCD than for the CDI group (p<0.05). In 4 of 5 recurrences in the CDI group, the volume of residual intracapsular air was sufficient after initial surgery. These results suggested that postoperative residual intracapsular air is a factor contributing to recurrence. Burr hole strict closed-system drainage is a simple, less invasive procedure with which to treat chronic subdural haematoma and the outcome is excellent. Furthermore, prevention of intracapsular air intrusion during surgery might help prevent recurrence.

Adult↗

PubMed2001

Myocardial interstitial norepinephrine and dihydroxyphenylglycol levels during ischemia and reperfusion.

OBJECTIVE: The aim was to elucidate the relation between norepinephrine (NE) release and intraneuronal NE kinetics in the ischemic region of the in vivo heart. METHODS: Using dialysis technique in the heart of anesthetized cats, we sampled dialysate from the ischemic region during 120-min coronary occlusion and reperfusion. Dialysate NE and dihydroxyphenylglycol (DHPG) contents were measured as indexes of myocardial interstitial NE and DHPG levels. RESULTS: Within 20 min of occlusion, interstitial NE levels increased while DHPG levels decreased. This NE increase was suppressed by omega-conotoxin GVIA and enhanced by desipramine. These data suggest that axoplasmic NE levels increased by neuronal reuptake following exocytotic release, while intraneuronal DHPG production was suppressed due to the reduced monoamine oxidase activity. After 20 min of occlusion, interstitial NE levels increased markedly, accompanied by increased DHPG levels. This NE increase was suppressed by desipramine. These findings imply that NE mobilization from stored vesicles to axoplasma exceeded outward NE transport through uptake(1) carrier in the amount of NE, and that a substantial increase in axoplasmic NE levels compensated for the reduced monoamine oxidase activity. After reperfusion, interstitial NE levels rapidly decreased while DHPG levels increased further. Both responses in NE and DHPG were suppressed by desipramine, indicating the involvement of recovered neuronal reuptake function. CONCLUSIONS: In the ischemic region, intraneuronal DHPG production was affected by alterations in monoamine oxidase activity, NE mobilization from stored vesicles, and carrier-mediated NE transport. The involvement of these factors in intraneuronal NE kinetics varied with the time of occlusion and reperfusion.

Animals↗