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Biomedical subjects

S Hitomi

Publications and source records attributed to S Hitomi.

At least 19 recordsLinked to original sources

Diagnosis and monitoring of human cytomegalovirus diseases in patients with human immunodeficiency virus infection by use of a real-time PCR assay.

We used a real-time PCR assay to measure human cytomegalovirus (HCMV) DNA load in whole blood and plasma of 70 patients who were infected with human immunodeficiency virus type 1. Break points of 3.0 x 10(3) copies/mL in whole blood and 1.0 x 10(3) copies/mL in plasma were well-correlated with the existence of definite HCMV disease (sensitivity, 93% and 86%; specificity, 89% and 85%; positive predictive value, 70% and 63%; and negative predictive value, 98% and 95%, respectively). In patients with < 50 cells/microL of CD4(+) T lymphocytes, positive predictive values increased to 78% and 71%, respectively. The viral loads of all patients who received anti-HCMV therapy declined to < or =2.0 x 10(2) copies/mL in parallel with the improvement of clinical symptoms. These findings show that the HCMV DNA load quantified with our method is a useful tool for diagnosis of HCMV diseases and for monitoring the disease activity in patients infected with HIV-1.

AIDS-Related Opportunistic Infections↗

A novel mouse beta-defensin, mBD-6, predominantly expressed in skeletal muscle.

Defensins comprise a family of cationic antimicrobial peptides that is characterized by the conserved 6 cysteine residues. They are expressed in the epithelial cells of various organs and are identified as key elements in the host defense system at the mucosal surface. We isolated a novel mouse beta-defensin gene from the bacterial artificial chromosome DNA containing the mouse beta-defensin-3 gene. The full-length cDNA was cloned from skeletal muscle cDNA and called mouse beta-defensin-6 (mBD-6). The predicted peptide conserved the 6-cysteine motif and had 59% amino acid sequence identity with mouse beta-defensin-3 and 59% identity with mouse beta-defensin-4. We demonstrated the expression of mBD-6 in skeletal muscle in addition to the esophagus, tongue, and trachea. In animal models of endotoxemia, mBD-6 expression was also induced in the lung. mBD-6 showed potent antimicrobial activity against Escherichia coli and would play an important role in host defense in the esophagus, airways, and skeletal muscle. mBD-6 is the first reported beta-defensin predominantly expressed in skeletal muscle. This unique tissue specificity suggests some novel physiological roles of this peptide family.

Amino Acid Sequence↗

Reperfusion lung injury after cold preservation correlates with decreased levels of intrapulmonary high-energy phosphates.

BACKGROUND: To evaluate the role of energy state in primary graft dysfunction, which is crucial in lung transplantation, we investigated the relationship between intrapulmonary high-energy phosphate compounds and reperfusion lung injury after cold preservation. METHODS: Using an isolated rat lung perfusion model with fresh rat blood as perfusate, rat lungs were exposed to various cold preservation periods (0, 6, 9, and 12 hr) and reperfused. RESULTS: We found that extending the preservation period exacerbated the pulmonary hemodynamics after reperfusion. The levels of intrapulmonary high-energy phosphate compounds did not change during cold preservation, but these levels after reperfusion decreased as the preservation period was prolonged. The pulmonary hemodynamics after reperfusion were inversely correlated with the intrapulmonary high-energy phosphate compound levels after reperfusion. Total adenine nucleotide and ATP were sensitive indicators of reperfusion lung injury after cold preservation. Energy charge was not a sensitive indicator. The decreased levels of intrapulmonary high-energy phosphate compounds after reperfusion following cold preservation period were partially caused by their decreased production. CONCLUSIONS: These results demonstrated that reperfusion lung injury after cold preservation was closely correlated with decreased levels of intrapulmonary high-energy phosphate compounds after reperfusion, although the levels of the intrapulmonary high-energy phosphate compounds did not change during cold preservation of up to 12 hr.

Adenine Nucleotides↗

Prognostic significance of cyclin E overexpression in resected non-small cell lung cancer.

Cyclin E plays a pivotal role in the regulation of G1-S transition and relates to malignant transformation of the cells. However, the clinical significance of cyclin E expression in patients with non-small cell lung cancer remains unknown. We examined the expression of cyclin E in 242 resected non-small cell lung cancer in pathological stages I-IIIa and analyzed its relation to clinicopathological factors. Cylin E overexpressions were observed frequently in deeply invasive tumors. Multivariate analysis revealed that complete resection, pathological stage, and cyclin E expression were independent prognostic indicators. When cyclin E and proliferating cell nuclear antigen are combined, the cases negative for both had a significantly better prognosis than the other cases. We concluded that cyclin E overexpression relates to deeply invasive tumors and is correlated with poor prognosis. New therapeutic options may be provided by combination of cyclin E expression and proliferating cell nuclear antigen overexpression.

Adenocarcinoma↗

Human thioredoxin attenuates hypoxia-reoxygenation injury of murine endothelial cells in a thiol-free condition.

The adult T cell leukemia-derived factor (ADF), or human thioredoxin (hTRX), has a radical scavenging effect similar to that of N-acetyl cysteine (NAC). We have recently shown that ADF/hTRX protects the lung and the heart from ischemia-reperfusion induced injury. To elucidate mechanisms of the protective effect, a hypoxia-reoxygenation (H-R) injury model was developed using a murine endothelial cell line, cultured in a thiol-free medium. In this condition, cells became much more vulnerable to H-R injury. The viability of cells decreased significantly after 1 h of hypoxic incubation followed by 1 h of reoxygenation. The injury was reduced by ADF/hTRX (100 microM) or NAC (10 mM). These two agents also demonstrated an additive protective effect. When cells were cultured in thiol-free medium for 2 h in a normoxic condition, intracellular hydrogen peroxide production was increased, which was associated with a decrease in glutathione level. NAC (10 mM) attenuated these changes whereas ADF/hTRX (100 microM) did not. These results suggest that although both ADF/hTRX and NAC protected cells from H-R injury, the underlying mechanisms are different. Because the cytoprotective effect of ADF/hTRX occurs in the thiol-free condition, it must be mediated via a novel mechanism other than enhancing thiol uptake. The additive cytoprotective effect between ADF/hTRX and NAC suggests that we should combine these two agents clinically.

Acetylcysteine↗

Pulmonary mucosa-associated lymphoid tissue lymphoma 8 years after resection of the same type of lymphoma of the liver.

A 64-year-old woman presented with hepatic and pulmonary tumors of mucosa-associated lymphoid tissue lymphoma occurring 8 years apart. The present case carries the possibility of pulmonary metastasis of hepatic lymphoma or double primary lymphoma. Mucosa-associated lymphoid tissue lymphomas tend to develop in the extranodal primary organ, rarely developing systemically among extranodal organs as in our case. Our experience is useful in understanding the progress and outcome of mucosa-associated lymphoid tissue lymphoma.

Female↗

Significance of cyclic adenosine monophosphate and nitroglycerin in ET-Kyoto solution for lung preservation.

BACKGROUND: We previously demonstrated that the supplement of both dibutyryl cyclic adenosine monophosphate (db-cAMP) and nitroglycerin to the conventional ET-Kyoto solution improved lung preservation significantly. However, the significance of each component in lung preservation remained unclear. We examined the efficacy of the two components on lung preservation in the current study. METHODS: Rat lung grafts (eight per group) were studied in an isolated lung perfusion model. Group 1 grafts were flushed and preserved with ET-Kyoto solution containing 2 mmol/L of db-cAMP. Group 2 grafts were flushed and preserved with ET-Kyoto solution containing 100 mg/L of nitroglycerin. In group 3, the grafts were flushed and preserved with ET-Kyoto solution containing neither db-cAMP nor nitroglycerin as control group. After 4-hour cold storage, the lung grafts were reperfused for 50 minutes. RESULTS: The lung grafts in groups 1 and 2 showed significantly better lung function after reperfusion than those in group 3 with regard to arterial oxygen tension, shunt fraction, peak inspiratory airway pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance. The supplementation of db-cAMP improved especially the pulmonary arterial pressure and pulmonary vascular resistance, while the supplementation of nitroglycerin improved especially the oxygenation and airway pressure of the grafts. CONCLUSIONS: Both of db-cAMP and nitroglycerin had beneficial effects on lung preservation and are essential to the ET-Kyoto solution. There was a difference between the two components in the effects on preserved lungs.

Animals↗

Evaluation of tracheo-bronchial wall invasion using transbronchial ultrasonography (TBUS).

BACKGROUND: Whereas accurate evaluation of tumor invasion into the tracheo-bronchial wall is a critical factor in decision-making of therapy for intra-thoracic malignancies, it is sometimes difficult with usual thoracic imaging techniques such as computed tomography. As recent progress in technology of ultrasonography is marked, usefulness of transbronchial ultrasonography (TBUS) in evaluation of tracheo-bronchial wall invasion was assessed. METHODS: Following routine fiberoptic bronchoscopy, an ultrasound probe (20 MHz) covered with a balloon sheath was inserted through the bronchoscope. After air present between the ultrasound probe and the tracheo-bronchial wall was eliminated with filling the balloon with distilled water, TBUS imaging was taken. RESULTS: With TBUS, normal tracheo-bronchial wall was represented as a five-layer structure at the cartilagenous portion and a three-layer structure at the membranous portion. Based on this normal TBUS imaging, tumor extent was judged in 35 patients with intra-thoracic malignancies. Among 25 patients with extra-wall tumor including esophageal cancer (n=15) and metastatic lymph nodes (n=7), tracheo-bronchial wall invasion was clearly demonstrated in nine patients, and no invasion was demonstrated in the other 16 patients. Among ten patients with tumor originating from the tracheo-bronchial wall, tumor extent beyond outer border of the wall was demonstrated with TBUS in five patients. These diagnoses were examined pathologically in 15 patients who underwent the operation, and the accuracy was 93.3%. CONCLUSIONS: It is suggested TBUS can be a useful diagnostic tool in evaluation of tumor invasion to the tracheo-bronchial wall.

Adult↗

Control of a methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit by unselective use of nasal mupirocin ointment.

In September 1996, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) colonization occurred in the neonatal intensive care unit (NICU) of our hospital. After failing to control the outbreak by conventional methods we implemented an intranasal blanket use programme of mupirocin ointment from the beginning of November 1997. In the programme, patients who had been carrying MRSA received intranasal administration of the ointment three times daily for the first three days and consecutively three times weekly, while newly admitted patients and those who had not been colonized were prophylactically medicated three times weekly. This blanket administration was executed for one month. Methicillin-resistant Staphylococcus aureus colonization became undetectable in all but one intubated inpatient who had already been colonized before the start of the programme, and no new acquisitions occurred until the middle of January 1998, seven weeks after the termination of the blanket use programme. The rate of colonized patients in the unit also decreased. During and after the programme, neither an increase in minimum inhibitory concentration for the antibiotic nor apparent adverse reactions in any of the treated patients were observed. We concluded that this procedure is an effective method of controlling an MRSA outbreak in an NICU when the outbreak cannot be managed with conventional measures.

Administration, Intranasal↗

Prognostic significance of proliferative activity in pN2 non-small-cell lung carcinomas and their mediastinal lymph node metastases.

OBJECTIVE: To investigate the expression of proliferating cell nuclear antigen (PCNA) in both primary tumor and lymph node metastases of pathologic stage IIIA N2 non-small-cell lung carcinoma (NSCLC) and the relation to prognosis. SUMMARY BACKGROUND DATA: Although the prognosis of pN2 NSCLC is poor in general, long-term survivors have been reported among patients with completely resected or clinical N0 disease and those with skip metastasis. However, few reports are available on preoperative prognostic predictors. Expression of PCNA is known to be associated with tumor proliferation and is correlated with the prognosis of several carcinomas. METHODS: Clinicopathologic factors were investigated in relation to prognosis in 76 patients with pathologic stage IIIA pN2 NSCLC from whom resected surgical specimens were available from both the primary tumor and lymph node metastases for evaluation of PCNA expression. RESULTS: A significant correlation was observed between PCNA labeling index in the primary tumor and that in lymph node metastases. The prognosis in patients with PCNA-negative primary tumor (5-year survival rate, 66.0%) was significantly more favorable than that of patients with PCNA-positive primary tumor (5-year survival rate, 21.5%). The prognosis in patients with PCNA-negative metastases was significantly more favorable than that of patients with PCNA-positive metastases. For clinical N2 disease also, the prognosis of patients with PCNA-negative primary tumor was favorable (5-year survival rate, 66.1%). Multivariate analyses showed that PCNA expression and complete resection were significant prognostic factors. CONCLUSIONS: Preoperatively diagnosed N2 NSCLC exhibiting negative PCNA expression in primary tumor or lymph node metastases is expected to result in a favorable postoperative prognosis and may be an indication for primary resection.

Aged↗

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↗

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↗

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↗