Incidence of penicillin-resistantstreptococcus pneumoniae in Japan, 1993–1995

The Working Group for PRSP was organized through the participation of 40 institutions to investigate the incidence of penicillin (Pc)-resistantStreptococcus pneumoniae (PRSP) in Japan. We collected 2410S. pneumoniae clinical isolates between October 1994 and March 1995. The susceptibility to Pc, erythromycin, and minocycline was determined by an agar dilution method using Mueller-Hinton agar supplemented with 5% sheep blood. Pc-susceptibleS. pneumoniae (PSSP) were defined as bacteria for which the minimum inhibitory concentration (MIC) was ≤0.06 μg/mL; Pc-intermediateS. pneumoniae (PISP) as those for which the MIC ranged from 0.125 to 0.25 μg/mL; PRSP, as those with a MIC≥0.5μg/mL. The incidence of resistant strains including PISP and PRSP was 41.8% in 1994 and 40.8% in 1995. Logistic regression analysis showed that PRSP was significantly more frequent in infants aged 0 to 2 years old than in the general population and PSSP was significantly more frequent in elderly patients aged 60 or older. The rate of PRSP was significantly higher in the throat than in the sputum. Among 10 regions studied nationwide, PRSP was detected less frequently in the areas of Hokkaido and Hokuriku and more frequently in the areas of Chugoku, Shikoku, and Kyushu. Most PRSP were resistant to erythromycin and minocycline. PSSP serotyping using the capsule-quellung reaction indicated a number of types. In contrast, most PISP and PRSP were serotyped to types 19, 23, and 6.     

Cytological findings of ROS1‐rearranged lung adenocarcinoma

ROS1‐rearranged lung adenocarcinoma has been recently identified. We report a case of ROS1‐rearranged lung adenocarcinoma with special emphasis on cytological findings. Here, we report a case of young woman with ROS1‐rearranged lung adenocarcinoma diagnosed by cytology and discuss the clinical, cytological, and molecular findings. Cytologically, the tumor consisted of small tight clusters of cells with high nuclear/cytoplasmic ratio. Nuclei were enlarged and small nucleoli were occasionally observed. Signet‐ring cells were focally identified. Neoplastic cells were positive for ROS1 immunocytochemistry. Subsequently, the translocation of ROS1 gene was confirmed in a histological specimen. In conclusion, the specific histology of adenocarcinoma on cytological materials should promote testing for ROS1 immunohistochemistry. Immunocytochemical detection of ROS1 protein helps identify patients suitable for molecular targeted therapy.     

A polymeric micelle MRI contrast agent with changeable relaxivity.

Polymeric micelles were formed from cationic polymers (polyallylamine or protamine) and anionic block copolymers (poly(ethylene glycol)-b-poly(aspartic acid) derivative) that bound Gd ions providing high contrasts in Magnetic Resonance Imaging (MRI) by shortening the T(1) longitudinal relaxation time of protons of water. The Gd-binding block copolymer alone showed high relaxivity (T(1)-shortening ability) values from 10 to 11 mol(-1) s(-1), while the polymeric micelles exhibited low relaxivity values from 2.1 to 3.6 mol(-1) s(-1). These findings point to the feasibility of a novel MRI contrast agent that selectively provides high contrasts at solid tumor sites owing to a dissociation of the micelle structures, while selective delivery to the tumor sites is achieved in the polymeric micelle form.     

Study of nasopharyngeal bacterial flora. Variations in nasopharyngeal bacterial flora in schoolchildren and adults when administered antimicrobial agents

Changes in nasopharyngeal bacterial flora in adults with acute upper respiratory tract infection on administration of antimicrobial agents were investigated, and how these changes contrasted with those in children. Many patients with acute sinusitis due to allergies, and patients with malignancy and diabetes mellitus were included in the investigation. The detection rates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the major bacteria of acute otitis media (AOM), were 22%, 10%, and 7% respectively, which were significantly lower than those for children. Gram stain examination of nasopharyngeal swab samples showed a significant relation between leukocyte infiltration and the detection amount of S. pneumoniae (P = 0.0086). A significant relation (P = 0.0134) was also observed when H. influenzae was simultaneously detected. No significant change in the three major AOM bacteria present in nasopharyngeal bacterial flora after administration of antimicrobial agents was observed. However, all S. pneumoniae and H. influenzae detected after antimicrobial agent administration had the β-lactam-resistance gene. It was observed that a significant improvement in leukocyte infiltration occurred 6 to 10 days after antimicrobial agent administration. In contrast, a significant improvement in children was observed at 2 to 5 days. In the adult subjects, this improvement was probably due to spontaneous remission rather than the effect of the antimicrobial agents. Although investigation of the long-term administration of antimicrobial agents was also conducted, its benefits for the patients were not elucidated.     

Leukotriene synthases and the receptors induced by peripheral nerve injury in the spinal cord contribute to the generation of neuropathic pain

Leukotrienes (LTs) belong to a large family of lipid mediators, termed eicosanoids, which are derived from arachidonic acids and released from the cell membrane by phospholipases. LTs are involved in the pathogenesis of inflammatory diseases, such as asthma, rheumatoid arthritis, and peripheral inflammatory pain. In the present study, we examined whether LTs were implicated in pathomechanism of neuropathic pain following peripheral nerve injury. Using the spared nerve injury (SNI) model in rats, we investigated the expression of LT synthases (5‐lipoxygenase; 5‐LO, Five lipoxygenase activating protein; FLAP, LTA4 hydrolase; LTA4h and LTC4 synthase; LTC4s) and receptors (BLT1, 2 and CysLT1, 2) mRNAs in the rat spinal cord. Semi‐quantitative RT‐PCR revealed that 5‐LO, FLAP, LTC4s, BLT1, and CysLT1 mRNAs increased following SNI, but not CysLT2 mRNAs. Using double labeling analysis of in situ hybridization with immunohistochemistry, we observed that 5‐LO, FLAP, and CysLT1 mRNAs were expressed in spinal microglia. LTA4h and LTC4s mRNAs were expressed in both spinal neurons and microglia. BLT1 mRNA was expressed in spinal neurons. The p38 mitogen‐activated protein kinase inhibitor, but not MEK inhibitor, reduced the increase in 5‐LO in spinal microglia. Continuous intrathecal administration of the 5‐LO inhibitor or BLT1 and CysLT1 receptor antagonists suppressed mechanical allodynia induced by SNI. Our findings suggest that the increase of LT synthesis in spinal microglia produced via p38 MAPK plays a role in the generation of neuropathic pain. © 2009 Wiley‐Liss, Inc.     

Methylmercury inhibits electron transport chain activity and induces cytochrome c release in cerebellum mitochondria

The involvement of oxidative stress has been suggested as a mechanism for toxicity caused by methylmercury (MeHg). One of the major critical sites for oxidative stress is the mitochondria. In this research, to clarify the target site in mitochondria affected by MeHg, the individual activities of the mitochondrial electron transport chain (ETC) (I～IV) were examined in the liver, cerebrum and cerebellum of MeHg-intoxicated rats. In addition, to elucidate the mechanism underlying MeHg toxicity, cytochrome c release, caspase 3 activity and histological study were examined in the cerebrum and cerebellum. The cerebellum was found to be an exclusive tissue in which significant MeHg-induced alterations were observed. The complex II activity in the cerebellum mitochondria significantly decreased after MeHg exposure. Cytochrome c release from mitochondria increased only in the cerebellum by MeHg exposure. However, no significant alterations in caspase 3 activity or histological structure were found in brain tissues. These results suggest that MeHg acts on the constituents of complex II in the cerebellum, and induces mitochondrial dysfunction, leading to a release of cytochrome c from mitochondria. These events were considered to occur at the early stage of MeHg intoxication.     

Recurrence of occult pneumococcal bacteremia by an identical strain in an apparently healthy child

This is the first report to describe an apparently healthy girl, who developed recurrent occult bacteremia by the same Streptococcus pneumoniae strain, at 11 and 15 months of age. The two separately isolated organisms were demonstrated to have the identical serotype (type 6B), antibiotic susceptibility (intermediately penicillin-resistant), genotypes of penicillin-binding proteins, and patterns of pulse-field gel electrophoresis. The serum levels of anti-type 6B antibodies showed poor responses after both bacteremic episodes, but other immunological workups did not demonstrate any abnormalities. This case indicates that occult bacteremia may recur due to an identical pneumococcal strain in an immunocompetent infant, and that early introduction of pneumococcal conjugate vaccine is necessary in Japan.     

Developmental activity of the renin-angiotensin system during the "critical period" modulates later L-NAME-induced hypertension and renal injury.

The incidence of hypertension and hypertensive renal disease is increasing worldwide, and new strategies to prevent these diseases need to be investigated. The aims of this study were 1) to examine if transient exposure to an angiotensin receptor blocker (ARB) during an early period in hypertension development confers protection against subsequent worsening of hypertension and renal injury induced by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and 2) conversely, to examine the effects of transient exposure to angiotensin II (Ang II) during the same period. First, spontaneously hypertensive rats (SHR) were treated transiently from age 3 to 10 weeks with an ARB (candesartan cilexetil), a calcium channel antagonist or a vasodilator, then taken off treatment for 2 months. Administration of L-NAME at age 18 weeks caused severe hypertension and renal injury. However, the rats that had been exposed to the ARB not only had a lower blood pressure, but also failed to show signs of renal injury or increase of oxidative stress. Furthermore, the elevation of components of the renin-angiotensin-aldosterone system was also suppressed in these rats. In the second study, Wistar-Kyoto rats (WKY) and SHR were exposed to Ang II from age 4 to 8 weeks. The follow-up showed that the blood pressures in the WKY remained elevated compared to controls, while the SHR had heightened increases in blood pressure, renal renin mRNA, and urinary 8-hyroxydeoxyguanosine after L-NAME administration. Together, these experiments demonstrate that transient treatment of rats during an early phase in the development of hypertension with an ARB suppresses the renin-angiotensin-aldosterone system and confers long-term protection against subsequent L-NAME-induced renal injury and increases in renal oxidative stress. Conversely, developmental exposure to Ang II during this "critical" period had the opposite effect, predisposing rats to higher blood pressure, renal injury, and oxidative stress after L-NAME administration.     

Perfusion CT of breast carcinoma: arterial perfusion of nonscirrhous carcinoma was higher than that of scirrhous carcinoma

RATIONALE AND OBJECTIVES: Our goals were to apply perfusion CT technique to breast tumor and to evaluate the correlation between arterial perfusion value and other tumor characteristics. MATERIALS AND METHODS: Thirty-one female patients with primary breast tumors were included in this study. A single-slice dynamic CT was performed after an intravenous bolus injection of contrast material (40 ml; 370 mg I/ml) at 8 ml/sec. The parameters were calculated on a pixel-by-pixel basis by using maximum slope method, and quantitative maps of arterial perfusion were created. Statistical correlation between tumor size, patient age, and perfusion were assessed. Differences in perfusion between scirrhous and nonscirrhous carcinoma were also assessed. RESULTS: Perfusion CT images were successfully created for 24 patients (mean age, 55.9 years old; range, 36-85 years). In five patients, dynamic CT was not performed due to lack of visualization of the breast tumor on unenhanced CT. In two patients, reliable perfusion CT image could not be created because of motion artifact. The mean perfusion for 24 tumors was 33.1 +/- 16.9 ml/min/100 ml (mean +/- SD; range, 14-78), and the tumor perfusion did not correlate with patient's age or tumor size (21.0 +/- 10.2 mm; range, 10-45 mm). The mean perfusion of nonscirrhous carcinoma (45.8 ml/min/100 ml; n = 11) was higher than that of scirrhous carcinoma (22.7 ml/min/100 ml; n = 11; P < .001). CONCLUSION: Determination of the perfusion of breast carcinoma is feasible by dynamic CT and can be performed during a routine CT study without much supplementary burden on the patient. There are differences in blood flow between scirrhous and nonscirrhous breast carcinoma, and further research is needed to determine the impact of this finding.