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Biomedical subjects

T Horii

Publications and source records attributed to T Horii.

At least 55 records · Page 3Linked to original sources

Serum factors governing intraerythrocytic development and cell cycle progression of Plasmodium falciparum.

Malaria is clinically manifested only when the human malaria parasites in the genus Plasmodium enter the obligatory intraerythrocytic life cycle. Elucidation for the roles of the serum, the key nutrient, and its components is then deemed essential for thorough understanding of the proliferation of Plasmodium cells at the erythrocytic stage. Fractionation and analysis of serum and its components was performed by chromatography, solvent extraction, and subsequent reconstitution experiments. Only fractions containing serum albumin (SA) from the serum and purified intact bovine serum albumin (BSA) showed comparable growth promoting activity with human serum (HS). Delipidated BSA can only effect parasite growth after reconstitution with lipids extracted from intact BSA. Fatty acid (FA) species in the neutral lipid fraction from intact BSA proved likewise when reconstituted with delipidated BSA. Furthermore, the involved FA species have to come in a pair of one saturated and one unsaturated, with palmitic and oleic acids as the best combination. The results were further substantiated by morphological analysis as well as biochemical analysis of the DNA synthesis during the intraerythrocytic development. This study can be a basis to explore the molecular mechanism of lipid traffic within the parasitized red blood cell (RBC), which can be an important adjunct to the development of drugs for malaria therapy.

Animals↗

Nontransplant cardiac surgery for end-stage cardiomyopathy.

OBJECTIVE: To treat end-stage cardiomyopathy, we evaluated endoventricular circular patch plasty, partial left ventriculectomy, and valvular reconstruction alone in our 2-year experience. METHODS: Among 86 patients with heart failure evaluated between December 1996 and February 1999, 33 patients with ischemic cardiomyopathy (25 men and 8 women; mean age 61 +/- 7.8 years; New York Heart Association class 3.5 +/- 0.5) were treated with endoventricular circular patch plasty combined with coronary bypass grafting (84%) and mitral reconstruction (36%). The other 53 patients with nonischemic cardiomyopathy (45 men and 8 women; mean age 48 +/- 14.3 years, New York Heart Association class 3.7 +/- 0.5), were treated by left ventricular reduction by partial left ventriculectomy (n = 37) or patch plasty (n = 3) and valve reconstruction alone (n = 13). The first 24 patients (group I) underwent ventriculectomy with or without valve reconstruction; the more recent 29 patients (group II) underwent left ventricular reduction (n = 16) or valve reconstruction alone (n = 13) on the basis of the intraoperative echocardiographic evaluation to observe changes of wall motion and thickness during cardiopulmonary bypass. RESULTS: Ischemic Group: Hospital mortality in elective (n = 26) and emergency (n = 7) operations was 4% and 43%, and 3 patients died in the late postoperative period. Mean New York Heart Association class and ejection fraction improved from 3.5 +/- 0.5 to 1.5 +/- 0.7 and from 23% +/- 7.7% to 36% +/- 8.6%, respectively. Left ventricular end-diastolic and end-systolic volume indexes decreased from 162 +/- 46 mL/m(2) to 110 +/- 39 mL/m(2) and from 130 +/- 47 mL/m(2) to 70 +/- 32 mL/m(2), respectively. Nonischemic Group: In 40 patients with left ventricular reduction, hospital mortality in elective (n = 33) and emergency (n = 7) operations was 6% and 86%, and 5 patients died in the late postoperative period. Mean New York Heart Association class and ejection fraction improved from 3.7 +/- 0.5 to 1.7 +/- 0.6 and from 18% +/- 6.4% to 31% +/- 5.9%. Left ventricular end-diastolic and end-systolic volume indexes decreased from 203 +/- 45 mL/m(2) to 110 +/- 37 mL/m(2) and from 164 +/- 40 mL/m(2) to 79 +/- 33 mL/m(2), respectively. In 13 patients undergoing valve reconstruction alone (12 mitral with or without tricuspid and 1 tricuspid plus left ventricular assist device), hospital mortality in elective (n = 9) and emergency (n = 4) operations was 0% and 50% with no late deaths. Mean New York Heart Association class and ejection fraction improved from 3.6 +/- 0.5 to 2.0 +/- 0.5 and from 22% +/- 6.0% to 30% +/- 14.5%, respectively. Mean left ventricular end-diastolic and end-systolic volume indexes decreased from 170 +/- 34 mL/m(2) to 150 +/- 50 mL/m(2) and from 140 +/- 38 mL/m(2) to 104 +/- 40 mL/m(2), respectively. Overall mortality decreased from 50% in group I to 10% in group II. The survival estimates at 2 years were 77% (confidence limits 57%-88%) in the ischemic group and 63% (confidence limits 47%-75%) in the nonischemic group (no significant difference). The analysis of our data showed that the factors influencing the surgical results for dilated cardiomyopathy were presence of severe mitral regurgitation, preoperative New York Heart Association functional class IV with emergency operation, and operative procedures with randomly performed partial left ventriculectomy without an intraoperative echo test. CONCLUSION: Endoventricular circular patch plasty, partial left ventriculectomy, and solo valve reconstruction can be performed with an acceptably low risk as elective operations. The selection of operative procedures in idiopathic dilated cardiomyopathy and avoidance of emergency surgery improved operative mortality and morbidity. Among patients who survived at least 1 year, there were no late deaths up to 30 months' follow-up.

Adolescent↗

Late angiographic result of using the right gastroepiploic artery as a graft.

OBJECTIVE: The angiographic patency of the right gastroepiploic artery graft used for coronary artery bypass grafting was studied during the late (5-10 years) postoperative period. METHODS: Among 936 patients undergoing a gastroepiploic artery graft for coronary artery bypass grafting between 1986 and 1999, postoperative angiographic restudy was conducted on 685 patients within 1 year (mean, 2.2 months), on 102 patients between 1 and 5 years (mean, 2.3 years), and on 52 patients between 5 and 10 years (mean, 7.8 years). RESULTS: The patency rate of the gastroepiploic artery graft was 94%, 88%, and 83% in each restudy group. The cumulative patency rate estimated by the Kaplan-Meier method was 96.6% at 1 month, 91.4% at 1 year, 80.5% at 5 years, and 62.5% at 10 years. Causes of late occlusion were primary anastomotic stenosis and anastomosis to a less critically stenosed coronary artery. Once the gastroepiploic artery was perfectly anastomosed to the coronary artery, which has tight stenosis and good runoff, late patency was good, and new stenosis in both the gastroepiploic artery trunk and the anastomotic site was uncommon. CONCLUSION: The gastroepiploic artery graft can be used effectively for coronary artery bypass for the long term with proper target selection.

Arteries↗

Firm adherence of Staphylococcus aureus and Staphylococcus epidermidis to human hair and effect of detergent treatment.

Staphylococcus aureus and S. epidermidis are common pathogens in hospitals, and care should be taken not to disseminate these organisms among patients. We have focused on human hair as a source of bacterial contamination. We treated hair with culture solutions of S. aureus and S. epidermidis, and then performed scanning electron microscopy. Bacteria were detected on the surface of the cuticles of the hair, and the attached bacteria were not completely removed even by repeated washing with detergents. These results suggested that hair could be a source of bacterial contamination and indicated the importance of decontamination of hair.

Bacterial Adhesion↗

Effect of subinhibitory concentrations of macrolides on expression of flagellin in Pseudomonas aeruginosa and Proteus mirabilis.

In the present study we showed by molecular analysis that the inhibition of motility by macrolides in Proteus mirabilis and Pseudomonas aeruginosa was well correlated with the loss of the expression of flagellin. Erythromycin, clarithromycin, and azithromycin at subinhibitory concentrations (sub-MICs) suppressed the expression of flagellin dose dependently. Azithromycin had the strongest inhibitory effect on the expression of P. aeruginosa flagellin, whereas 16-membered rokitamycin had only a weak inhibitory effect. These results indicate the potential effectiveness of sub-MICs of erythromycin, clarithromycin, and azithromycin for the treatment of patients with P. mirabilis and P. aeruginosa infections.

Anti-Bacterial Agents↗

[Aortic valve/root replacement using a stentless bioprosthesis (Medtronic Freestyle valve)].

BACKGROUND: The purpose of the study is to assess the clinical and hemodynamic performance of aortic valve replacement (AVR) with the Freestyle bioprosthesis. METHODS: Twenty-one patients received AVR with a Freestyle aortic root bio-prosthesis between May 1998 and October 1999. Eighteen patients underwent AVR with subcoronary method and three patients with aortic root (full root) method. Patients were evaluated postoperatively at discharge by clinical examination and color Doppler echocardiography. RESULTS: There was one death due to multi-organ failure. No patients experienced valve deterioration, paravalvular leak, unacceptable hemodynamic performance, nor thromboembolic event. Excellent function is demonstrated by very low gradient (mean gradient 7.2 +/- 4.7 mmHg) through aortic valve and no significant aortic regurgitation (none: 11, trivial/mild: 10). All patients had been in New York Heart Association Functional Class III and IV preoperatively, and after surgery, 17 patients were in Class I, and 3 were in Class II. CONCLUSION: The Freestyle bioprosthesis has good clinical and hemodynamic performance without Coumadin. Further follow-up is required to evaluated valve durability.

Adult↗

[Coronary artery bypass grafting without cardiopulmonary bypass in 200 patients].

OBJECTIVES: To evaluate the efficacy of off pump coronary artery bypass grafting (CABG), results in the initial consecutive 200 patients were reviewed. METHODS: Between October 1996 and December 1999, 200 patients underwent CABG without cardiopulmonary bypass. There were 146 men and 54 women aged from 27 to 89 years (mean 68 years). Single, double, triple and left main disease were noted in 94, 55, 33 and 18 patients, respectively, with a mean ejection fraction of 51%. Preoperative complications were previous stroke in 34 patients, chronic renal failure in 22 patients, previous CABG in 18 patients, and aortoiliac aneurysm or occlusive disease in 14 patients. Fifty-five patients (28%) were 75 years or older. Surgical approach was made through a midsternal incision including lower half small sternotomy in 105 patients, left anterior small thoracotomy in 92 and small epigastric incision (gastroepiploic-right coronary anastomosis) in 3. Mean number of distal anastomoses was 1.3 (range 1-4). Anastomosis was performed in 189 left anterior descending, 13 diagonal, 27 circumflex and 41 right coronary arteries. The conduits were 174 internal thoracic, 10 internal thoracic-inferior epigastric composite, 22 right gastroepiploic and 5 radial arteries, and 50 saphenous vein grafts. Four patients underwent combined off pump CABG and transmyocardial laser revascularization, and 36 patients underwent hybrid (off pump CABG and angioplasty) revascularization. RESULTS: Four patients (2.0%) died in the hospital due to intestinal necrosis in 2 patients, postoperative aortic dissection in one, and multiorgan failure with stroke in one. No serious ventricular tachyarrhythmia or use of intraaortic balloon pump occurred. Perioperative myocardial infarction was noted in one patient. Stroke occurred in 4 patients (2.0%) but 3 patients recovered in a short period. Three-year survival and cardiac event free rate were 90.3% and 81.1% by the Kaplan-Meier method. Postoperative angiographic study showed excellent patent graft in 92% of grafts (192/209), stenosed (> or = 50%) graft in 5% (10/209) and occlusion in 3% (7/209). CONCLUSIONS: Off pump CABG can be performed safely and effectively in both high risk and low risk patients with coronary artery disease. Refinement of surgical technique and equipment will make this procedure more useful.

Adult↗

Apoptotic cell death in steroid induced osteonecrosis: an experimental study in rabbits.

OBJECTIVE: We investigated apoptosis, i.e., programmed cell death, in steroid induced osteonecrosis in a rabbit model. METHODS: Forty-four adult Japanese White rabbits were divided into 3 groups: Group A were untreated controls and had a subsequent 8 week no-treatment period; Group B received intramuscular injection of methylprednisolone 4 mg/kg once weekly for 4 weeks; and Group C received the same treatment and had a subsequent 8 week no-treatment period. At the end of each period, all animals were sacrificed and tissue samples were obtained from the femur and humerus for histopathologic examination. Terminal deoxynucleotidyl transferase (TdT) mediated deoxyuridine triphosphate (dUTP) biotin nick end labeling (TUNEL) was used to detect fragmented DNA known to be associated with apoptotic cell death. RESULTS: Group A rabbits did not develop osteonecrosis-like lesions (ONL) in the femur and humerus, and few TUNEL positive cells were observed in bone marrow cells. In Group B, ONL developed in 11/15 rabbits, and many TUNEL positive cells were found in the area surrounding ONL. In Group C, ONL were found in 6/10 rabbits, but only a few TUNEL positive cells were present around the lesion. CONCLUSION: These findings revealed that apoptosis occurs in the early stage of steroid induced osteonecrosis.

Animals↗

Sequence diversity of serine repeat antigen gene exon II of Plasmodium falciparum in worldwide collected wild isolates.

Field isolates of Plasmodium falciparum collected from endemic areas of Southeast Asia, Solomon Islands, tropical African countries and Brazil were analyzed for the genetic diversity of the exon II of serine repeat antigen gene (SERA) by sequencing of genomic DNA. Of sixty-nine isolates, as compared to the reported FCR3, K1 and Honduras-1 types of exon II sequences, 5, 9 and 20 new allelic forms were found in 23 isolates of the FCR3 type, 36 of the K1 type and 10 of the Honduras-1 type. A group of novel non-synonymous substitutions, 4 new insertions and 3 new deletions of octamer units were found in the octamer repeat region (OR) of the exon II, and most of them clustered within a 40-residues domain. An octamer "SNPVSSEP" revealed in the OR was confirmed as a new repeat unit. Based on the sequences of the serine repeat region (SR) of the exon II, the allelic forms of the Honduras-1 type were conjectured to be the recombinant forms between the K1 type and FCR3 type. The allelic forms of K1 type with less or more repeat serine residues in the serine stretch of the SR than the reported 21 serine residues had most of the variations in the OR. Moreover, a biased geographical distribution of allelic forms was observed. Isolates from African and Southeast Asian countries accounted for most of the new allelic forms (29/33). All of the three types were detected in Southeast Asia but none of the FCR3 type in Africa. One of two groups of FCR3 new allelic forms was found solely in Brazil while another was mainly in Solomon Islands.

Alleles↗

Role of multiple efflux pumps in Escherichia coli in indole expulsion.

Escherichia coli chromosome encodes several multidrug transporters. Despite their protective function against antibacterial agents, the specific physiological actions of these transporters are not fully understood. E. coli produces indole, a metabolite of tryptophan, under physiological conditions. Defined inactivation of the acrEF gene, the product of which is known as an energy-dependent multiple drug efflux pump, decreased indole excretion while reintroduction of the acrEF gene restored it. A DeltaacrEF mutant accumulated more intracellular indole than the parent. This mutant was more susceptible to the growth-inhibitory effect of indole than the parent. These results indicate that the AcrEF system plays a significant role in indole efflux.

Carrier Proteins↗

Four critical aspartic acid residues potentially involved in the catalytic mechanism of Escherichia coli K-12 WaaR.

Escherichia coli K-12 WaaR is a non-processive alpha-1,2 glucosyltransferase, involved in the synthesis of the R-core of lipopolysaccharide. WaaR possesses the four conserved structural regions I, II, III and IV, each presumably involved in the mechanistic function in catalysis. Regions I and III contain the pair of strictly conserved Asp residues. Asp-129, 131 (region I) and 215, 217 (region III) of WaaR were individually converted to Asn by the site-directed mutagenesis of the waaR gene. All mutated enzymes were inactive, supporting the model for an alpha-glycosyl transfer reaction where the pair of strictly conserved aspartic acid residues in regions I and III play a critical role in the catalytic function.

Aspartic Acid↗

DNA immunization with Plasmodium falciparum serine repeat antigen: regulation of humoral immune response by coinoculation of cytokine expression plasmid.

We immunized mice with plasmid expressing the 47-kDa amino-terminal domain of the Plasmodium falciparum serine repeat antigen (SERA) using gene gun and investigated humoral immune response to SERA antigen. Significant SERA-specific IgG was observed in BALB/c mice after immunization three times with SERA expression plasmid. Furthermore, these levels were increased by the coinoculation of cytokine (IFN-gamma, IL-4, GM-CSF, or IL-12) expression plasmid. In respect to the SERA-specific Ig subclasses, coinoculation of IFN-gamma, GM-CSF, or IL-12 expression plasmid increased the levels of SERA-specific IgG2a, and these were much higher than that in mice immunized with SERA expression plasmid alone. In contrast to the SERA-specific IgG2a, coinoculation of any cytokine expression plasmid did not change the levels of SERA-specific IgG1. These results indicate that cytokine expression plasmid enhances and regulates humoral immune response elicited by SERA DNA immunization.

Animals↗

Utilization of exogenous folate in the human malaria parasite Plasmodium falciparum and its critical role in antifolate drug synergy.

The antifolate combination pyrimethamine/sulphadoxine (PYR/SDX; Fansidar) is frequently used to combat chloroquine-resistant malaria. Its success depends upon pronounced synergy between the two components, which target dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) in the folate pathway. This synergy permits clearance of parasites resistant to either drug alone, but its molecular basis is still unexplained. Plasmodium falciparum can use exogenous folate, which is normally present in vivo, bypassing SDX inhibition of DHPS and, apparently, precluding synergy under these conditions. However, we have measured parasite inhibition by SDX/PYR combinations in assays in which folate levels are strictly controlled. In parasites that use exogenous folate efficiently, SDX inhibition can be restored by levels of PYR significantly lower than those required to inhibit DHFR. Isobolograms show that the degree of synergy between PYR and SDX is highly dependent upon prevailing folate concentrations and are indicative of PYR acting to block folate uptake and/or utilization. No significant synergy was observed at physiological drug levels when PYR/SDX acted on purified DHFR, whether wild type or mutant. We conclude that the primary basis for antifolate synergy in these organisms arises from PYR targeting a site (or sites) in addition to DHFR, which restores DHPS as a relevant target for SDX.

4-Aminobenzoic Acid↗

Antibacterial activities of new synthetic divalent cation chelators.

A series of new synthetic ligand compounds which chelate divalent cations was examined for the antibacterial activities of the compounds. Only 2 of 14 synthetic chelators, 9-trans-anthryl-1, 4, 8, 11-tetraaza-tetradecane (No. 6) and bis(2-pyridyl)methylamine (No. 13) showed antibacterial activities, whereas none of the diamines, hydrophilic triamines nor tetramines showed antibacterial activities. Chelators No. 6 and No. 13 inhibited the growth of both Gram-negative and -positive bacteria at doses of 25-200 microg/ml, comparable to those of common antibiotics such as polymixin B, fosfomycin and macrolides. Ethylenediaminetetraacetate (EDTA) potentiated these antibacterial activities, whereas an inhibitory effect of Mg2+ on the MICs of these chelators was observed. Moreover, these chelators enhanced the leakage of periplasmic beta-lactamase. It is therefore suggested that chelators No. 6 and No. 13 disrupt both the membranes and cytoplasmic functions of bacteria, resulting in cell death.

Anthracenes↗

Are autoantibodies against Lewis antigens involved in the pathogenesis of Helicobacter pylori-induced peptic ulcers?

We examined whether anti-Lewis x (Le(x)) and y (Le(y)) autoantibodies affect the pathogenesis of Helicobacter pylori-induced peptic ulcers. Of 11 patients with peptic ulcers, 10 patients had both anti-Le(x) and -Le(y) immunoglobulin G (IgG) antibodies, and 1 patient had only anti-Le(x) antibody. After successful eradication, we measured the serum titer of anti-Le(x) and -Le(y) antibodies. Six patients had a reduction of the titers of anti-Le(x) and/or -Le(y) antibodies, whereas no notable changes were detected in 5 patients in the follow-up. This result suggests that anti-Le(x) and -Le(y) autoantibodies had no critical role in the development of H. pylori-induced peptic ulcer.

Autoantibodies↗

Pathological effect of synthetic cereulide, an emetic toxin of Bacillus cereus, is reversible in mice.

Cereulide is the causative toxin of the emetic type of food-borne illness caused by Bacillus cereus. This toxin was previously shown to be associated with fulminant liver failure in a human case. Mice were injected i.p. with synthetic cereulide and the development of histopathological changes was examined. Hepatocytes showed mitochondrial swelling with loss of cristae, and dose-dependent increase of small fatty droplets. These microsteatotic hepatocytes were distributed mainly in the pericentral area. At higher cereulide doses, massive degeneration of hepatocytes occurred. The serum values of hepatic enzymes were highest on days 2-3 after the inoculation of cereulide, and rapidly decreased thereafter. General recovery from the pathological changes and regeneration of hepatocytes was observed after 4 weeks.

Animals↗

Emergence of fosfomycin-resistant isolates of Shiga-like toxin-producing Escherichia coli O26.

We evaluated the susceptibilities of 129 Shiga-like toxin-producing Escherichia coli (STEC) isolates to various antibiotics. The numbers of isolates for which MICs were high (> or = 128 micrograms/ml) were as follows: 5 for fosfomycin, 14 for ampicillin, 1 for cefaclor, 6 for kanamycin, 22 for tetracycline, and 2 for doxycycline. For two isolates of STEC O26 MICs of fosfomycin were high (1,024 and 512 micrograms/ml, respectively). Conjugation experiments and glutathione S-transferase assays suggested that the fosfomycin resistance in these isolates was determined not by a plasmid but chromosomally. The amount of active intracellular fosfomycin in these STEC isolates was 100- to 200-fold less than that in E. coli C600 harboring pREFTT47B408 in the presence of either L-alpha-glycerophosphate or glucose-6-phosphate. Cloning, sequencing, and Northern blot analysis demonstrated that the transcriptional level of the murA gene encoding UDP-N-acetylglucosamine enolpyruvoyl transferase in these isolates was greater than that in E. coli C600. Our results suggest that the fosfomycin resistance in these STEC isolates is due to concurrent effects of alteration of the glpT and/or uhp transport systems and of the enhanced transcription of the murA gene.

Alkyl and Aryl Transferases↗

Immune responses induced by gene gun or intramuscular injection of DNA vaccines that express immunogenic regions of the serine repeat antigen from Plasmodium falciparum.

The liver- and blood-stage-expressed serine repeat antigen (SERA) of Plasmodium falciparum is a candidate protein for a human malaria vaccine. We compared the immune responses induced in mice immunized with SERA-expressing plasmid DNA vaccines delivered by intramuscular (i.m.) injection or delivered intradermally by Gene Gun immunization. Mice were immunized with a pcdna3 plasmid encoding the entire 47-kDa domain of SERA (amino acids 17 to 382) or the N-terminal domain (amino acids 17 to 110) of SERA. Minimal antibody responses were detected following DNA vaccination with the N-terminal domain of SERA, suggesting that the N-terminal domain alone is not highly immunogenic by this route of vaccine delivery. Immunization of mice by Gene Gun delivery of the 47-kDa domain of SERA elicited a significantly higher serum antibody titer to the antigen than immunization of mice by i.m. injection with the same plasmid did. The predominant isotype subclass of the antibodies elicited to the SERA protein following i.m. and Gene Gun immunizations with SERA plasmid DNA was immunoglobulin G1. Coimmunization of mice with SERA plasmid DNA and a plasmid expressing the hepatitis B surface antigen (pCMV-s) by the i.m. route resulted in higher anti-SERA titers than those generated in mice immunized with the SERA DNA plasmid alone. Vaccination with DNA may provide a viable alternative or may be used in conjunction with protein-based subunit vaccines to maximize the efficacy of a human malaria vaccine that includes immunogenic regions of the SERA protein.

Animals↗