Therapeutic effect of antimicrobial drugs against experimental infections due toYersinia pestis in mice

Although there are effective antibacterial agents against plague, newer antibacterial agents have been developed which show more potent activity against other bacterial organisms, but have not been tested againstYersinia pestis. A strain ofYersinia pestis was selected (no. 22; National Institute of Infectious Diseases, Tokyo, Japan) that caused a systemic infection in mice.Y. pestis no. 22 was intraperitoneally inoculated into DDY-strain mice, and 13 oral or 6 injectable antibacterial drugs given to the infected mice at varying doses 1 and 24 hours after infection. Levofloxacin, sparfloxacin and ofloxacin were the most effective oral agents against the infection, and prulifloxacin and pazufloxacin were also effective but to a lesser extent. Also, gentamicin and arbekacin were the most potent injectable antibacterial agents againstY. pestis. These results suggest that there are several new drugs, both oral and injectable, which exert excellent in vivo antibacterial activity against a mouse infection model and may be useful for the clinical treatment of plague.     

Cancer detection using a PET tracer, 11C-glycylsarcosine, targeted to H+/peptide transporter.

H+/peptide transporter, PEPT1, is functionally expressed in some human cancer cell lines and might be a candidate molecular target for detection of cancers in vivo using PET. The aim of the present study was to establish a novel tumor-imaging technology using a PET tracer targeted to H+/peptide transporter(s). We also compared the tracer with 18F-FDG, focusing on the specificity of their accumulation between tumor and inflammatory tissues. METHODS: A dipeptide PET tracer, 11C-glycylsarcosine (11C-Gly-Sar), was injected intravenously into athymic mice transplanted with human pancreatic, prostate, and gastric cancer cells. The distribution patterns of 11C-Gly-Sar and 18F-FDG in the tumor-bearing mice, and in mice with inflammatory tissue, were assessed by imaging with a positron planar imaging system (PPIS). Tissue distributions of tracer radioactivity were also measured. The expression levels of PEPT1 and PEPT2 (PEPTs) proteins in tumor xenografts and inflammatory tissue were examined by immunohistochemical analysis. The messenger RNA expression levels of PEPTs in 58 available cancer cell lines were quantified by means of real-time polymerase chain reaction. RESULTS: All 3 tumor xenografts were well visualized with the PPIS after injection of 11C-Gly-Sar. Expression of PEPTs in those xenografts was confirmed by immunohistochemical analysis. Tumor-to-blood concentration ratios of 11C-Gly-Sar increased in a time-dependent manner and were much higher than unity. Most of the radioactivity found in the tumor tissue was recovered as the intact tracer. These results indicated that 11C-Gly-Sar was taken up by the PEPTs in tumor xenografts. It is noteworthy that 11C-Gly-Sar was minimally present in inflammatory tissues that expressed no PEPT1 or PEPT2 protein, whereas 18F-FDG was highly accumulated, with the values of the selectivity index being >25.1 and 0.72 for 11C-Gly-Sar and 18F-FDG, respectively. The mRNAs of PEPT1 and PEPT2 were expressed in 27.6% and 93.1%, respectively, of the cancer cell lines examined in the present study. CONCLUSION: The present study indicates that 11C-Gly-Sar is a promising tumor-imaging agent and is superior to 18F-FDG for distinguishing between tumors and inflammatory tissue. Because PEPTs were ubiquitously expressed in various types of tumor cells examined, 11C-Gly-Sar could be useful for the detection of many types of cancers.     

Establishment of a monoclonal antibody directed to the minor novel gangliosides in bovine brain and cultured neural cell lines

We established a MAb N-25 reacted with a minor unknown antigen (AgX) in a commercially available GQ1b sample. It also recognized minor antigens in bovine brain (X-1, 2, 3, 4 and 5) and cultured neural cell lines (X-1). AgX is identical to X-5. X-5 is sialidase sensitive and has the common structure as X-1, which is resorcinol positive. These results suggested that novel gangliosides exist in bovine brain and neural cell lines.     

Impact of unilateral interposition sural nerve graft on the recovery of sexual function after radical prostatectomy in Japanese men: A preliminary study

PURPOSE: To determine the effect of an interposition nerve graft on sexual function after radical prostatectomy. METHODS: This study includes 64 patients, without hormonal therapy, who underwent a radical prostatectomy and intraoperative electrophysiological confirmation of cavernous nerve preservation. Twelve patients underwent a unilateral interposition sural nerve graft (UNG) for the resected neurovascular bundle. Twenty-one and 31 patients underwent bilateral nerve-sparing (BNS) and unilateral nerve-sparing (UNS) surgery without a nerve graft, respectively. As the age of patients was significantly younger in the UNG group than in the other groups, age-matched analysis also was conducted. Sexual function, evaluated by a self-administered questionnaire using the University of California Los Angeles-Prostate Cancer Index, was compared statistically among the three groups. RESULTS: In the age-matched analysis, the postoperative sexual function (SXF) score of the UNG group showed an intermediate level of recovery between those of the BNS and UNS groups at 12 months and reached the same level as the score at 12 months of the BNS group at 18 months postoperatively. The difference in the SXF score between the UNG and UNS groups began to appear after 6 months postoperatively and increased steadily with time. However, the background factors, such as the baseline SXF score, the usage rate of phosphodiesterase 5 inhibitors, and the rate of comorbidities were different between the UNG and UNS groups. CONCLUSIONS: The difference of the SXF score between the UNG and UNS groups increased with time after 6 months postoperatively. However, it might be difficult at present to attribute a better recovery of the SXF score to the nerve graft because of the difference in the background factors between the groups.     

Exo-focal postischemic neuronal damage in the rat brain: alteration of [H]forskolin binding using in vitro autoradiography

We studied the alteration of intracellular signal transduction using quantitative autoradiography of the second messenger system in order to clarify the mechanisms of delayed neuronal damage in the remote areas of rat brain after transient focal ischemia. Chronological changes of [³H]forskolin binding sites were measured to demonstrate the striatal-nigral pathway after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by 3 h, 6 h, 1 day, 3 days, 1 week, 2 weeks and 4 weeks of recirculation. [³H]Forskolin binding sites were found to be markedly decreased in the lateral segment of the caudate putamen supplied by the occluded MCA after 90 min of ischemia with no recirculation. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, marked reduction of [³H]forskolin binding sites was observed in the ipsilateral substantia nigra which lay outside the ischemic areas. This postischemic delayed phenomenon observed in the substantia nigra developed concurrently with ⁴⁵Ca accumulation, which was detected there in our previous study. The delayed reduction of [³H]forskolin binding sites in the substantia nigra observed in the present study indicates that striatonigral terminal degeneration at presynaptic sites is caused by precedent ischemic damage of the ipsilateral caudate putamen and that exo-focal postischemic neuronal death is caused by a transsynaptic process associated with the ischemic foci.     

Absence of highly homologous sequence to HTLV-I in Japanese multiple sclerosis

We tried to detect HTLV-I-related sequences in Japanese patients with multiple sclerosis with a highly sensitive method that employs the polymerase chain reaction (PCR) of genomic DNA followed by Southern blot hybridization analysis. To amplify HTLV-I sequences, we used primers for LTR, pol, gag, and env coding regions. Fourteen patients with definite MS, 14 disease controls, 12 normal controls, and 3 patients with HTLV-I-associated myelopathy (HAM) were investigated. Results of particle aggregation assay for HTLV-I antibodies were negative in serum from all subjects except for the 3 HAM patients. Neither the 14 MS patients nor the 26 controls showed the presence of any highly homologous sequences to HTLV-I. We did observe faint signals for gag, pol, and env coding regions only at low stringent hybridization in some MS patients as well as some normal controls. The nucleotide sequence analysis of the faint bands was more homologous to major histocompatibility complex molecules than the HTLV-I genome.     

The prognostic significance of nuclear DNA content in non-small-cell lung carcinoma

The nuclear DNA content of paraffin-embedded specimens of primary non-small-cell lung carcinomas was analysed using flow cytometry in 210 patients (80 squamous cell carcinomas, 99 adenocarcinomas, 19 large cell carcinomas and 15 others). The relationship between nuclear DNA content and prognostic factors was studied using multivariate analysis with Cox's proportional hazard model. 1) The frequency of DNA aneuploidy was 77.3% among 210 patients, and it significantly (p less than 0.05) increased with advanced stage and the presence of lymph node metastasis. 2) The patients with DNA aneuploid tumors had a significantly (p less than 0.001) less favorable prognosis than those with DNA diploid tumors among 179 patients with non-small-cell lung carcinomas. Similar results were demonstrated in 79 patients with stage I carcinomas and in 85 patients who underwent absolute curative resection. 3) Multivariate analysis using Cox's proportional hazard model showed that DNA ploidy was an independent prognostic factor for survival. Especially in the patients with absolute curative resection, DNA ploidy was the most important prognostic factor. In conclusion, flow cytometric nuclear DNA content analysis provided useful biological information, and DNA ploidy was an important and major independent prognostic factor in non-small-cell lung carcinoma.