Observation of Zn-photoprotoporphyrin red Autofluorescence in human bronchial cancer using color-fluorescence endoscopy.

BACKGROUND: We observed red autofluorescence emanating from bronchial cancer lesions using a sensitive color-fluorescence endoscopy system. We investigated to clarify the origin of the red autofluorescence. METHODS: The wavelengths of the red autofluorescence emanating from lesions were measured in eight patients using a spectrum analyzer and compared based on pathologic findings. Red autofluorescence at 617.3, 617.4, 619.0, and 617.1 nm was emitted by normal bronchus, inflamed tissue, tissue exhibiting mild dysplasia, and malignant lesions, respectively. Protoporphyrin, uroporphyrin, and coproporphyrin, the major porphyrin derivatives in human blood, were purchased to determine which porphyrin derivative is the source of red fluorescence when acquired de novo. We synthesized photoporphyrin, Zn-protoporphyrin and Zn-photoprotoporphyrin from protoporphyrin. RESULTS: Coproporphyrin and uroporphyrin emitted only weak fluorescence. Fluorescence was emitted by our synthesized Zn-photoprotoporphyrin at 625.5 nm and by photoprotoporphyrin at 664.0 nm. CONCLUSIONS: From these results, we conclude that Zn-photoprotoporphyrin was the source of the red autofluorescence observed in bronchial lesions. Zn-protoporphyrin is converted to Zn-photoprotoporphyrin by radiation with excitation light. Our results suggest that red autofluorescence emanating from Zn-photoprotoporphyrin in human tissues could interfere with photodynamic diagnosis using porphyrin derivatives such as Photofrin® and Lazerphyrin® with a sensitive endoscopy system, because color cameras cannot differentiate Zn-photoprotoporphyrin red fluorescence from that of other porphyrin derivatives.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents. Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S. pneumoniae were 1.1% and 0.0%, respectively. Among H. influenzae, 17.6% of them were found to be ß-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be ß-lactamase-non-producing ABPC-resistant and 11.0% to be ß-lactamase-producing ABPC-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 2.9% and 0.6%, respectively. Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

[Comparison between predicted equations obtained by standard Japanese values and present predicted equations for vital capacity and forced expiratory volume in one second].

Until recently, predicted values of vital capacity (VC) and forced expiratory volume in one second (FEV1) have been calculated with Baldwin's equation (VC-B) and Berglund's equation (FEV1-B) respectively, in Japan. Due to several problems using these equations, new prediction equations of VC (VC-J) and FEV1 (FEV1-J), which were created using data from healthy Japanese, were provided by the Japanese Respiratory Society in 2001. In the present study, we studied the validity of these prediction equations. Also, we compared the outcomes of patients who match respiratory handicap "indexes" with VC-B and VC-J. The subjects were all adult patients whose respiratory function was tested in Asahikawa Medical College Hospital between 1998 and 2006. Cases which were diagnosed as contractive respiratory disorder increased approximately 2-fold when %VC was calculated with VC-J compared with VC-B. Grade 4 or higher respiratory handicap scores increased 20% if the index was calculated with VC-J compared with VC-B. There was no significant difference in mortality between the respiratory handicap grade 3 scores calculated with VC-J and VC-B. Also, there was no significant difference in mortality between grade 4 respiratory handicap scores calculated with VC-J and VC-B. These findings suggest that the prediction equations using Japanese data increase the number of predicted respiratory disorders, and those additional cases have the same prognoses as those cases diagnosed with the former criteria.

Human small cell lung cancer cells express functional VEGF receptors, VEGFR-2 and VEGFR-3.

Studies have suggested that the vascular endothelial growth factors (VEGFs)/VEGF receptors (VEGF-Rs) system plays an important role in tumour growth and metastasis. We conducted the present study to clarify whether small cell lung cancer (SCLC) cells express functional VEGF-Rs and VEGFs, and their biological significance in the SCLC progression. We examined expression of VEGF and VEGF-C, and their receptors, VEGFR-2 and VEGFR-3, in five SCLC cell lines, NCI-H82, H209, H510, H526 and H660, by Western blotting. We evaluated whether hypoxic conditions up-regulate these protein expressions. We also examined whether VEGF addition and VEGF-D addition cause phosphorylation of the mitogen-activated protein kinase (MAPK) as well as VEGFR-2 and VEGFR-3. Further, we investigated whether VEGF addition and VEGF-D addition induced the proliferation and migration of the SCLC cells. VEGF, VEGF-C, VEGFR-2 and VEGFR-3 were detectable by Western blotting in all five SCLC cell lines,. The VEGF-Rs and VEGFs expression levels were increased by an incubation under hypoxic conditions in NCI-H82. VEGF addition and VEGF-D addition caused phosphorylation of MAPK as well as the VEGF-Rs themselves, and induced proliferation and migration of the SCLC cells. These results suggested potential of VEGF signal-pathway inhibitors as anti-cancer agents in SCLC treatment disturbing growth and migration of the cancer cells.

Alterations in penicillin binding protein gene of Streptococcus pneumoniae and their correlation with susceptibility patterns.

Penicillin binding protein (pbp) gene alterations of 328 clinical isolates of Streptococcus pneumoniae were examined for a correlation with their antibiotic-resistance. The frequency of penicillin G (PEN-G) resistance was determined to clarify susceptibility to several antibiotics, namely PEN-G, ampicillin, sulbactam/ampicillin, cefozopram, panipenem (PAPM), clarithromycin (CLR), azithromycin (AZM) and levofloxacin (LVX). Oligonucleotide primers for three pbp genes (pbp1a, pbp2x and pbp2b) were used to detect mutations in pbp. Of the strains, 25.9% were classified as Pen-Gs, 68.0% as Pen-Gir and 6.1% as Pen-Gr. The polymerase chain reaction product for wild-type pbp1a was found in 185 isolates, that for wild-type pbp2x was found in 66 isolates and that for wild-type pbp2b was found in 213 isolates. None of these three genes was detectable in 100 isolates while all of them were detected in 64 isolates (1aw/2xw/2bw). Of those 64 isolates with 1aw/2xw/2bw, the minimum inhibitory concentration (MIC) of PEN-G was < or =0.06 mg/l for 54 isolates and 0.12 mg/l for 10 isolates. Of the 272 strains for which the MIC of PAPM was < or =0.03 mg/l, there were 85 Pen-Gs, 184 Pen-Gir and three Pen-Gr isolates. Three strains for which the MIC of LVX was > or =4.0 mg/l included one Pen-Gs and two Pen-Gir isolates. The MICs of CLR correlated significantly with those of AZM. The MIC of CLR was > or =1 mg/l for 216 isolates, and the MIC of AZM was > or =1 mg/l for 244 of them. These data suggested that PAPM may be effective against S. pneumoniae infection, although acquisition of resistance should be considered. LVX also seemed to be effective against S. pneumoniae.

Small cell lung cancer cells express EGFR and tyrosine phosphorylation of EGFR is inhibited by gefitinib ("Iressa", ZD1839).

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib ("Iressa", ZD1839) has demonstrated anti-tumor activity in non-small cell lung cancer (NSCLC) and has been approved in over 20 countries. NSCLC has been reported to express high levels of EGFR. However, gefitinib appears to be more effective against adenocarcinoma than squamous cell carcinoma, the latter expressing more EGFR. In the present study, we evaluated the effect of gefitinib against the small cell lung cancer (SCLC) cell lines NCI-H82, NCI-H209, NCI-H510, NCI-H526 and NCI-H660. SCLC has been reported to express a low to undetectable level of EGFR. We compared the effects of gefitinib between cell lines with detectable and undetectable EGFR expression. First, we evaluated expression levels of EGFR and HER2/neu by Western blotting and immunoprecipitation respectively; EGFR protein was detected in two of the five SCLC cell lines, whereas HER2/neu was not detected in any. Next, we analyzed expression levels of phosphorylated ERK1/2 and compared these results with EGFR (HER-1/ErbB1) and HER2/neu (ErbB2) expression levels, as EGFR conducts signals through Ras-Raf-MAPK pathway; gefitinib inhibited phosphorylation of ERK1/2 by EGF addition in cell lines with detectable and undetectable EGFR expression. These data suggest that gefitinib is potentially effective against cancers with low EGFR expression such as SCLC.

Renal abscess with Morganella morganii complicating leukemoid reaction.

We report a case of leukemoid reaction (LR) complicating renal abscess caused by Morganella morganii infection in an 80-year-old man. On administration, laboratory tests revealed white blood cell count of 76160 /microL and C reactive protein 3.09 mg/dL. Although chronic myeloid leukemia was suspected, bcr/abl fusion transcript was not observed. Contrast enhanced computer tomography imaging of the abdomen showed abscess in the right kidney. M. morganii was detected repeatedly in material of liquid from the abscess and arterial blood culture. To our knowledge, this is the first case of M. morganii infection complicating LR.