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S Hitomi

Publications and source records attributed to S Hitomi.

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

Effect of ions on antibacterial activity of human beta defensin 2.

Human beta defensin 2 (HBD-2), the most recently discovered human defensin, has been considered to work as a host defense substance against microbial infection. Using Escherichia coli ATCC 25922, we investigated how some cations and anions influenced the antimicrobial activity of HBD-2. This activity, measured in 10 mM phosphate buffer at a concentration of 20 microg/ml, reduced significantly in the presence of 100 and 150 mM sodium or potassium chloride. The reduction was not significantly different when the total amounts of sodium and potassium ions were equal. The kind and the valence of anions (chlorine and sulfate ions) did not affect the bactericidal activity as long as the concentrations of sodium ions were equal. Divalent ions (calcium and magnesium ions) added to 10 mM of Tris buffer significantly inactivated HBD-2 at much lower concentrations (more than or equal to 0.01 mM and 0.05 mM, respectively) than the monovalent ions did. These findings suggest that HBD-2 kills the bacteria through at least two phases, which are affected independently by either monovalent or divalent ions and unaffected by anions.

Anti-Bacterial Agents↗
PubMed2000

Susceptibility to vancomycin of methicillin-resistant Staphylococcus aureus isolated in a university hospital in Japan.

Intravenous vancomycin was approved in 1991 in Japan and has been widely used for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Consequently, ever since the initial discovery of vancomycin intermediate-resistant S. aureus in Japan, the vancomycin resistance of this organism has been a great concern in clinical settings. We investigated whether vancomycin resistance had emerged in MRSA isolated in our hospital since the approval of the use of intravenous vancomycin. Vancomycin susceptibility was evaluated on the basis of minimum inhibitory concentrations determined by the agar dilution method and a heterogeneous resistance examination. The median minimum inhibitory concentration of the 69 MRSA strains isolated in 1988 and the 74 isolated in 1998 was 0.75 microgram/ml and 1.0 microgram/ml, respectively (p < 0.001), however, all of the strains were classified in the susceptible group. None of them was an MRSA heterogeneously resistant to vancomycin (hetero-VRSA), which has been defined as a strain having a 1/10(6) or greater heterogeneously resistant subpopulation to vancomycin. In another set of investigations, no hetero-VRSA were found among 12 other MRSA strains isolated after intravenous administration of vancomycin for 14 or more days (range: 14 to 77 days). We conclude that while the use of intravenous vancomycin may have slightly lowered the vancomycin susceptibility of MRSA in our hospital, the decrease in so small that it may not be significant clinically. In addition, no hetero-VRSA were found in our hospial.

Aged↗
PubMed2000

Cytoprotective effects of nitroglycerin in ischemia-reperfusion-induced lung injury.

Prevention of ischemia-reperfusion (IR) injury is crucial for successful lung transplantation. We investigated whether a nitric oxide donor, nitroglycerin (NTG), could suppress the oxidative stress of IR injury and improve pulmonary function after reperfusion in an ex vivo rat lung perfusion model. In Fresh group of animals, the lungs were flushed with perfusate, followed immediately by reperfusion, and no lung injury was observed. In NTG- and NTG+ groups of animals, the lungs were flushed with perfusate alone or perfusate containing NTG, respectively. Harvested lung and heart blocks from these latter two groups were immersed in the corresponding perfusate at 4 degrees C for 15 h, and were then reperfused for 60 min. Reperfusion induced pulmonary edema in the NTG- group, but not in the NTG+ group. Shunt fractions in NTG+ group were significantly lower than in the NTG- group throughout reperfusion. NTG had no effect on pulmonary arterial pressure or myeloperoxidase activity. In contrast, oxidative DNA damage assessed immunohistochemically with a monoclonal antibody against 8-hydroxy-2'-deoxyguanosine (8-OHdG) was significantly increased in the NTG- group, in the order alveolar epithelium > pulmonary endothelium > bronchial epithelium. NTG treatment significantly decreased staining with the anti-8-OHdG antibody in all three areas of tissue. Therefore, administration of NTG attenuates the oxidative stress of IR injury, and may improve pulmonary function after reperfusion.

Animals↗
PubMed2000

Long-term clomipramine treatment upregulates forebrain acetylcholine muscarinic receptors, and reduces behavioural sensitivity to scopolamine in mice.

We have investigated the effects of long-term treatment with clomipramine, a tricyclic antidepressant, on central muscarinic acetylcholine receptors (mAChR) in mice. Repeated clomipramine administration resulted in an increase in the forebrain receptor density value (Bmax) for [3H]quinuclidinyl benzilate, a muscarinic ligand (P < 0.05), that was dependent on dose per administration (saline or 5, 10, or 20 mg kg(-1) once a day for 7 days) and number of days treated (20 mg kg(-1) for 1, 3, 5, or 7 days). No change in apparent affinity (defined as the reciprocal of the dissociation constant) (KD) occurred. Seven daily treatments with clomipramine (saline or 5, 10, or 20 mg kg(-1)) reduced hyperlocomotion induced by scopolamine (0.5 mg kg(-1), s.c.) dose-dependently, and the effect of 20 mg kg(-1) clomipramine was significant (P < 0.05). These results suggest that an upregulation of mAChR is produced by repeated clomipramine administration, and such a change is responsible for the decreased sensitivity to the muscarinic antagonist scopolamine.

Animals↗
PubMed2000

[Endoscopic approach to pulmonary diseases: Bronchoscopy for critical respiratory care in neonates, infants, and children].

Of the 605 pediatric patients admitted to our intensive care unit during the past 6 years, 90 underwent 380 bronchoscopies for diagnostic and therapeutic purposes. The indications for bronchoscopy were atelectasis/retention of airway secretion (n = 52), pneumonia (n = 31), airway bleeding (n = 14), pulmonary edema (n = 11), tracheobronchomalacia/airway stenosis (n = 11), and airway foreign body/aspiration (n = 7). Visualization of the airway was helpful for the diagnosis of respiratory problems; in 9 infants, bronchoscopy revealed tracheobronchial stenosis which other diagnostic modalities failed to detect. In 25 of the 31 patients with pneumonia, specimens taken by bronchoscopy were positive for specific pathogens. Bronchoscopy also proved to have significant therapeutic value, especially for airway cleaning; bronchial suctioning resulted in immediate reexpansion of the collapsed lung in 25 of 34 cases of physiotherapy-resistant atelectasis. A rigid bronchoscope was used to remove airway foreign body in 2 cases. Prototype channeled-ultrathin fiberscopes were utilized in 99 of 380 bronchoscopies. No complications were noted except for severe hypoxia and bradycardia in one infant. We conclude that bronchoscopy is a safe and useful modality for the critical respiratory care of infants and children.

Adolescent↗
PubMed2000

[Gene examination methods (detection and genotyping of resistant genes)--VRE].

There are six types of resistant genes in vancomycin-resistant enterococci: vanA, vanB, vanC-1, vanC-2, vanC-3, and vanD. The typing of the resistant genes is essential in clinical settings because the kind of a resistant gene implies susceptibility of an organism to glycopeptides and because strict infection control practices are required when vanA or vanB gene, which is encoded on plasmids and transmissible to other organisms, is detected. We describe methods of detecting and typing vancomycin-resistant genes, which are routinely performed in our laboratory.

Enterococcus↗
PubMed2000

Intratumoral expression of thymidylate synthase and dihydropyrimidine dehydrogenase in non-small cell lung cancer patients treated with 5-FU-based chemotherapy.

5-fluorouracil (5-FU) has been used widely, including in gastrointestinal cancer, breast cancer, and non-small cell lung cancer (NSCLC), and its efficacy has been reported to be associated with intratumoral expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). In order to clarify the clinical value of their expression in NSCLC patients treated with 5-FU, we investigated intratumoral expression of TS and DPD immunohistochemically. Of the 68 tumors studied, 40 carcinomas (58. 8%) had high TS expression, and 33 carcinomas (48.5%) had high DPD expression. The 5-year survival rate of the patients with high-TS tumors was significantly lower than that of the patients with low-TS tumors (P=0.0267), and the 5-year survival rate of the patients with high-DPD tumors was significantly lower than that of the patients with low-DPD tumors (P=0.0268). The Cox regression analysis of prognostic variables for NSCLC patients treated with 5-FU demonstrated that the simultaneous evaluation for both TS and DPD expression was found to be a significant indicator of a poor prognosis (P=0.0043). Our results demonstrated that the evaluation of intratumoral TS and DPD activity can be used to accurately predict responsiveness to 5-FU-based chemotherapy in NSCLC patients.

Adult↗
PubMed1999

Expression of proliferating cell nuclear antigen and CD44 variant isoforms in the primary and metastatic sites of nonsmall cell lung carcinoma with intrapulmonary metastases.

BACKGROUND: To the authors' knowledge the prognosis of patients with intrapulmonary metastases (PM) of nonsmall cell lung carcinoma (NSCLC) has not yet been clarified fully and little is known regarding the characteristic changes that occur during the metastatic process, nor of their clinical significance. METHODS: Formalin fixed and paraffin embedded material of primary and metastatic lesions resected from 34 patients with PM of NSCLC were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44 and its variant isoforms. RESULTS: Patients with NSCLC expressing PCNA in the primary tumor site (79.4%) showed a significantly poorer survival (5-year survival rate of 20.2%) compared with the 5-year survival rate of 57.1% for patients not expressing PCNA in the primary tumor site (P = 0.048). Patients expressing PCNA in the metastatic site (88.2%) also showed a significantly poorer prognosis than those not expressing PCNA (P = 0. 036). Patients with squamous cell carcinoma expressed CD44 variant exon 6 (CD44v6) at a significantly higher rate than adenocarcinoma patients (P = 0.0164), but expression of CD44v6 was not a significant prognostic factor. Concordance of PCNA and CD44v6 expression between the primary and corresponding metastatic sites was observed in 65% of patients (22 of 34 patients) but no difference in prognosis was observed in relation to this concordance. Cox multivariate analyses indicated that expression of PCNA was a significant prognostic indicator for both primary and metastatic sites (P = 0.014 and P = 0.0095, respectively). CONCLUSIONS: This study demonstrated that PCNA expression was a significant prognostic factor for both primary and metastatic lesions in PM patients. CD44v6 showed histogenesis of the tumor, but no relation with the prognosis could be ascertained.

Adenocarcinoma↗
PubMed1999

Role of saccharides on lung preservation.

BACKGROUND: Saccharides are considered to play a role as osmotic impermeants and serve as an energy source for the organ during ischemia. However, previous studies on the effectiveness of saccharides on organ preservation have yielded conflicting results. We compared the preservative effects of a monosaccharide (glucose), disaccharides (trehalose, maltose, sucrose), and a trisaccharide (raffinose) to investigate whether the effects of saccharides on lung preservation depend on their molecular weight, energy-level maintenance, and cytoprotective effects. METHODS: We used an ex vivo rat lung model using homologous blood as the perfusate. In the fresh group, the lungs were reperfused immediately after flush. In the other groups, the lungs were flushed with one of the solutions containing glucose, trehalose, maltose, sucrose, or raffinose and preserved for 14 hours. RESULTS: The results of the trehalose group were comparable to those of the fresh group. The glucose, maltose, and raffinose groups showed significantly higher levels of shunt fraction, pulmonary artery pressure, and peak inspiratory pressure compared with the fresh and trehalose groups. There were no differences among the groups in the levels of total adenine nucleotides, adenosine triphosphate of the lung after flush, and preservation. However, after reperfusion, levels of total adenine nucleotides became significantly lower in the glucose, sucrose, maltose, and raffinose groups. Ultrastructural examination revealed endothelial cell injury in the glucose, sucrose, maltose, and raffinose groups. CONCLUSIONS: These results show that the effects of saccharides may depend on their cytoprotective effect rather than on impermeant activity or energy-level maintenance of the preserved lung. Trehalose proved to be superior to the other saccharides.

Adenine Nucleotides↗
PubMed1999

Pharmacokinetics of cisplatin in analbuminemic rats.

The effect of protein binding on the pharmacokinetics of cisplatin (cis-diamminedichloroplatinum (II); CDDP) has been studied in analbuminemic rats, which genetically lack albumins, in comparison with normal rats. CDDP was reported to highly bind to serum components, and the major binder was thought to be an albumin. However, there were no significant differences in the serum disappearance profiles of platinum after intravenous (iv) bolus injection of CDDP to analbuminemic rats as compared with normal rats. The total body clearance, Cl(tot), of platinum in normal rats was 48.7+/-22.0 mL h(-1) (5 mg kg(-1)), 55.9+/-4.04 mL h(-1) (10 mg kg(-1)) and 49.0+/-3.57 mL h(-1) (20 mg kg(-1)), whereas Cl(tot) in analbuminemic rats was 52.0+/-8.48 mL h(-1) (5 mg kg(-1)), 62.9+/-10. 8 mL h(-1) (10 mg kg(-1)) and 62.8+/-6.81 mL h(-1) (20 mg kg(-1)). The serum blood urea nitrogen (BUN) and creatinine levels at 6 h after iv injection were higher in both groups of rats who received CDDP than those of pre-dose level. However, there were no significant differences in the renal function tests between analbuminemic rats and normal rats. The binding of CDDP to the serum samples obtained from analbuminemic rats and normal rats was measured by a centrifuging filtration method. The binding percentages were 68.0+/-5.9% (2.0 microg mL(-1)), 56.8+/-4.1% (5.0 microg mL(-1)) and 64.6+/-4.4% (10.0 microg mL(-1)) in analbuminemic rats and 52.9+/-3.5% (2.0 microg mL(-1)), 52.2+/-3.4% (5.0 microg mL(-1)), 56.9+/-1.9% (10.0 microg mL(-1)) in normal rats. Higher binding percentages were obtained in analbuminemic rats than in normal rats. In vitro binding studies under the two incubation conditions (5 min and 2 h) showed that the binding percentages of CDDP to serum proteins were 59.2+/-3.2% (5 min) and 72.3+/-6.5% (2 h) for albumin, 42.3+/-1.9% (5 min) and 39.5+/-2.5% (2 h) for alpha(1)-acid glycoprotein (AAG) and 51.7+/-5.3% (5 min) and 49. 2+/-1.9% (2 h) for gamma-globulin. From these studies, it was elucidated that albumin is not the major ligand in the rat serum and that other proteins also have important roles in the pharmacokinetics of CDDP.

Animals↗
PubMed1999

Postoperative adjuvant chemotherapy with PVM (Cisplatin + Vindesine + Mitomycin C) and UFT (Uracil + Tegaful) in resected stage I-II NSCLC (non-small cell lung cancer): a randomized clinical trial. West Japan Study Group for lung cancer surgery (WJSG).

OBJECTIVE: The West Japan Study Group For Lung Cancer Surgery (WJSG) conducted a randomized controlled trial in order to assess the usefulness of adjuvant chemotherapy for NSCLC. METHODS: Patients with completely resected NSCLC (stages I and II) were enrolled in the trial. These patients were randomized into two groups: a surgery alone group; and a chemotherapy group which received intravenous administration of two courses of 4-week PVM chemotherapy (80 mg/m2 of Cisplatin on day 1, 2-3 mg/m2 of Vindesine on day 1 and/or day 8, and 8 mg/m2 of Mitomycin C on day 1), after which they took 400 mg/day of UFT (Uracil + Tegaful) orally for 1 year. RESULTS: Among 229 patients registered for the study from August 1988 to July 1990, 225 were available cases (116 patients in the surgery alone group, and 109 patients in the chemotherapy group). No bias in prognostic factors could be found between the two groups. The 5-year survival rate was 71.1% for the surgery-alone group and 76.8% for the chemotherapy group with no significant difference observed. However, subset analysis demonstrated that PVM therapy improved the post operative survival of pT1N0 patients (the 5-year survival rate: 75.3% for the surgery alone group, and 90.7% for the chemotherapy group P<0.05). CONCLUSIONS: It is interesting to find that among pT1N0 patients, who were not regarded as a target of chemotherapy, those receiving chemotherapy showed significantly better prognostic results. These findings suggest the necessity of further studies on the adjuvant chemotherapy, even in the early stages.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Activation of human T lymphocytes by ganglioside-containing liposomes.

We investigated the in vitro stimulatory effect of ganglioside (GM3, GD1a, GD1b, GT1b, or GQ1b)-containing liposomes on human immune cells. The effect of ganglioside-containing liposomes on the concentration of cytoplasmic free calcium ions ([Ca2+]i) in human immunocytes was examined using the confocal laser fluorescence microscopic method. The GD1a- and GT1b-containing liposomes significantly increased [Ca2+]i of human T lymphocytes compared with the GM3-, GD1b- and GQ1b-containing ones. The response of CD8+ and CD4+ cells was significantly higher than that of CD20+ cells. Our results show that the increase in [Ca2+]i may be caused by not the number of sialic acids contained in the gangliosides but the conformation of the sialic acid moiety to protrude exteriorly from the liposomal membrane surface, and that a sort of receptor recognizing the sialic acid moiety exists on human T lymphocytes (both CD8+ and CD4+ cells), which may be involved in the activation of the cells. The present results are almost the same as those obtained for the rat T lymphocyte system previously reported. This clearly confirms that a sort of ganglioside surely stimulates T lymphocytes directly, which is not species-specific but conserved in humans and rats among animal species.

Animals↗
PubMed1999

Clinical application of biodegradable rib connecting pins in thoracotomy.

BACKGROUND: To assess the usefulness in rib reconstruction of biodegradable connecting pins made of polylactide (PLA), PLA rib pins were compared with conventional non-absorbent aluminous ceramic rib pins (alumina rib pins) in terms of their ability for fixing and healing of cut ribs in thoracic surgery. METHODS: There were 13 cases of rib fixation after thoracotomy using PLA rib pins and 11 cases using alumina rib pins, all of which were inserted into the medulla of the stump of the ribs that had been cut at thoracotomy to secure a larger surgical field. The observation period was 6 months after the operation. RESULTS: The degree of vertical shift of the ribs connected with PLA rib pins was significantly reduced compared with the degree using alumina rib pins. In chest radiographs clear zones around the pins, indicating a delay in bone neogenesis, were observed frequently around the alumina rib pins but were absent around the PLA rib pins. Osteosynthesis using PLA rib pins was significantly more favorable than with alumina rib pins. CONCLUSIONS: These results demonstrated that the PLA rib pin was superior to the alumina rib pin for fixing and healing of the cut rib.

Adult↗
PubMed1999

Expression of thymidylate synthase in human non-small cell lung cancer.

5-Fluorouracil (5-FU) has been used worldwide, and the correlation between its effects and thymidylate synthase (TS) expression has been reported in gastrointestinal malignancy. But the significance of TS expression for 5-FU-based chemotherapy has rarely been reported in non-small cell lung cancer (NSCLC). We investigated surgically resected specimens of 23 consecutive patients with previously untreated NSCLC. We used immunohistochemistry and western blot analysis with anti-TS polyclonal antibody to evaluate the existence of TS, and fluorodeoxyuridine-5'-monophosphate (FdUMP) binding assay to evaluate the enzymic activity of TS. We found that 14 samples (60.9%) were positive immunohistochemically, and that the results of immunohistochemistry closely reflected the enzymic activity measured by FdUMP binding assay (ranging from 1.8 to 56.9 pmol/g protein). These results seem to support our experience that 5-FU and its derivatives are clinically significantly effective as a postoperative adjuvant chemotherapy against NSCLC.

Adult↗
PubMed1999

p53 status predicts the efficacy of postoperative oral administration of tegafur for completely resected non-small cell lung cancer.

Although postoperative adjuvant therapy for non-small cell lung cancer (NSCLC) had not been reported to be effective, it has been reported recently that oral administration of tegafur (1-[2-tetrahydrofuryl]-5-fluorouracil, FT) may improve the postoperative prognosis. In the present paper, to examine whether p53 status affects the efficacy of FT as postoperative adjuvant chemotherapy for NSCLC, a total of 236 consecutive patients with completely resected pathologic stage I-IIIa NSCLC were retrospectively reviewed. p53 status was determined by immunohistochemical staining. For all patients, the 5-year survival rate of patients with FT administration (FT group) was 78.1%, being significantly higher than that (69.1%) of patients without FT administration (control group) (P=0.046). For patients without immunohistochemical evidence of p53 overexpression, the 5-year survival rate in the FT group was 87.1%, being significantly higher than that (74.0%) in the control group (P=0.036). This demonstrates an improvement of postoperative prognosis by FT administration. On the other hand, for patients with p53 overexpression, there was no significant difference in the postoperative prognosis between the FT group and the control group (5-year survival rate 63.2% and 60.1%, respectively; P=0.514), demonstrating that FT administration was not effective for these patients. In conclusion, p53 status may be useful for predicting the efficacy of postoperative adjuvant chemotherapy using FT. A prospective randomized study stratified by p53 status is needed to clarify the effect of postoperative FT administration.

Administration, Oral↗
PubMed1999

Mitochondrial injuries in rat lungs preserved for 17 h: An ultrastructural study.

Mitochondria of the small vasculature endothelial cells were examined in preserved rat lungs before and after reperfusion, and the ultrastructural changes were correlated with pulmonary function after reperfusion. Rat lungs were flushed with perfusate and prostaglandin E1 and divided into five groups (n = 5 in each group): group A, normal control group; group B, University of Wisconsin solution; group C, Euro-Collins solution; group D, ET-Kyoto solution, and group E, new ET-Kyoto solution. After preservation at 4 degrees C for 17 h, the left lungs were reperfused at 37 degrees C for 60 min. Tissue was sampled and mitochondria of the small vasculature endothelial cells were ultrastructurally analyzed by transmission electron microscopy before and after reperfusion. The ultrastructure of the mitochondria was well maintained in groups A, B and E before and after reperfusion. In group C, the number of severely degenerated mitochondria in the sectional area of 100 microm2 before reperfusion was 18.0 +/- 3.9, which was significantly larger than in the other groups (p < 0.01), and the total number of mitochondria significantly decreased with reperfusion (from 24.8 +/- 3.5 to 8.2 +/- 2.4, p < 0.05). In group C, the shunt fraction, mean pulmonary arterial pressure and the wet-dry ratio of the lung tissue after reperfusion C were significantly higher than in the other groups (p < 0.05; 76.3 +/- 1.5%, 54.8 +/- 4.2 mm Hg, and 20.6 +/- 2.5, respectively). A positive correlation was found between the percentage of the mitochondrial degeneration before reperfusion and the physiological parameters after reperfusion. Mitochondrial damage associated with cold ischemia is probably involved in lung injury caused by cold preservation and reperfusion.

Animals↗
PubMed1999

Influence of deflated and anaerobic conditions during cold storage on rat lungs.

Energy depletion closely correlates with ischemia-reperfusion (I-R) injury in solid organs, but there has been no conclusion about the lungs that contain air. We investigated the alveolar state during cold storage and its relation to energy metabolism and I-R injury in an ex vivo rat lung model. The lung was deflated (DEF group) or inflated with either room air (RA group) or nitrogen (N(2) group) for 6 h at 4 degrees C, and reperfusion samples of buffer and bronchoalveolar lavage fluid (BALF) was collected (n = 6, each). Furthermore, the static lung compliance, the intrapulmonary high-energy phosphates, lactate, and pyruvate were measured. The pulmonary functions of the DEF and N(2) groups were significantly worse than those of the RA group. In the N(2) group, the intrapulmonary levels of energy charge and pyruvate/lactate ratio were significantly lower than those in the DEF and RA groups, whereas there were no significant differences between the DEF and RA groups. In the DEF group, total protein and lactate dehydrogenase (LDH) in the BALF were significantly higher whereas the static lung compliance was significantly lower compared with the N(2) and RA groups. We concluded that aerobic metabolism would be essential for attenuating I-R injury of the lung, and inflation of the alveoli would be necessary for avoiding mechanical damage during reexpansion.

Air↗