Operational lumped constant for FDG in normal adult male rats.

We determined an operational value for the lumped constant to be used in measurements of the local rate of cerebral glucose use (lCMR(glc)) with FDG in normal adult male rats. METHODS: The standard quantitative autoradiographic method was used with 2-deoxy-d-(14)C-glucose ((14)C-DG) and with (14)C-FDG in awake normal adult male rats. Timed arterial blood samples were drawn for 45 min after the bolus and assayed for plasma glucose and (14)C concentrations. At the end of the 45-min experimental period, the rats were killed, and their brains were removed and divided in half sagittally. One hemisphere was immediately frozen and assayed for local (14)C concentrations by quantitative autoradiography; the other was weighed, homogenized in t-octylphenoxypolyethoxyethanol solution, and assayed for (14)C concentrations in the whole brain by liquid scintillation counting. Paired rats (3 pairs), one in each pair receiving (14)C-DG and the other receiving (14)C-FDG, were studied in parallel on the same day. Additional unpaired animals (n = 8) were studied with either (14)C-DG or (14)C-FDG but not in parallel on the same day. To calculate the lCMR(glc) in rats studied with (14)C-FDG, the rate constants for (14)C-FDG were estimated from the (14)C-DG values determined for rats and the (14)C-FDG/(14)C-DG ratios determined for humans. In all of the rats studied with either (14)C-DG or (14)C-FDG, the lCMR(glc) was first calculated in 12 representative brain structures with the lumped constant of 0.48 previously determined for (14)C-DG in rats. The ratio of the lCMR(glc) thus determined with (14)C-FDG to that determined with (14)C-DG for each structure was then multiplied by the lumped constant for (14)C-DG to estimate the lumped constant for (14)C-FDG. The lCMR(glc) and the lumped constant for FDG in the brain as a whole were similarly estimated from the tracer concentrations in the brain homogenates. RESULTS: The mean values for the lumped constant for FDG were found to be 0.71 and 0.70 in the autoradiographic assays and the assays with brain homogenates, respectively. CONCLUSION: The appropriate value for the lumped constant to be used in determinations of the lCMR(glc) in normal adult male rat studies with (18)F-FDG and small-animal PET scanners is 0.71.     

Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease

BACKGROUND: Although some laboratory findings are known to be indicators of the risk of giant coronary aneurysm formation among Kawasaki disease patients, an appropriate cut-off point to predict aneurysm formation is not clear. METHODS: One hundred and five patients with giant coronary aneurysms were selected from the 15th and 16th nationwide surveys of Kawasaki disease in Japan. A total of 2936 patients without Kawasaki disease were recruited from a single hospital as a control group. Odds ratios were calculated for six laboratory data with specific values as cut-off points. Receiver operating characteristic (ROC) curves were observed to determine the most appropriate laboratory tests and cut-off points. RESULTS: Hematocrit, leukocyte count, neutrophil proportion, and hemoglobin had one or more peaks of odds ratio for specific cut-off points, but they did not have a clear cut-off point for the predictor according to the receiver operating characteristic curves. Alanine aminotransferase (ALT) increased the risk of giant coronary aneurysms continuously so no clearly appropriate cut-off point was identified. Serum sodium concentration of 135 mEq/L had a peak of odds ratio, and those with <135 mEq/L had the highest odds ratio (4.78). This value seemed appropriate with a sensitivity of 78% and specificity of 57%, although the predictive positive value was as small as 5%. CONCLUSION: The author's propose that a serum sodium concentration of <135 mEq/L at the patient's first visit to hospital may be a predictor of giant coronary aneurysms due to Kawasaki disease.     

Prognostic factors in patients with ipsilateral pulmonary metastasis from non-small cell lung cancer.

OBJECTIVE: Pulmonary metastasis of non-small cell lung cancer is classified as an advanced disease stage, with limited indications for surgical treatment. However, the prognosis of patients with pulmonary metastasis of non-small cell lung cancer is better than that of patients with distant metastases. The purpose of the present study was to analyze and detect possible prognostic factors in surgically treated patients with ipsilateral pulmonary metastasis of non-small cell lung cancer. METHODS: Among 1198 patients with non-small cell lung cancer who underwent surgery at Kurashiki Central Hospital (Okayama, Japan) from April 1982 to March 2004, a total of 48 (4.0%) patients with pathologically diagnosed ipsilateral pulmonary metastasis were retrospectively evaluated. The median follow-up time was 20.5 months (range 1-103 months) and 37 patients (77.1%) were completely followed up until their death or more than 5 years after the operation. RESULTS: Among the 48 patients, 31 (64.6%) patients had metastatic nodules in the same lobe as the primary tumor (PM1) and 17 (35.4%) patients had metastatic nodules in different ipsilateral lobes (PM2). There was no significant difference in survival between patients with PM1 and the other patients with pT4-stage IIIB, or between patients with ipsilateral PM2 and the other patients with stage IV. Univariate analysis of postoperative survival stratified according to clinicopathologic factors revealed significant differences for the radicality of resection (complete vs. incomplete), tumor size (0-30 vs. >30mm) and pathological nodal (pN) factor (among pN0, pN1 and pN2-3). Multivariate analysis revealed that tumor size (0-30 vs. >30mm) and pN factor (pN0-1 vs. pN2-3) were independent prognostic factors. CONCLUSIONS: The results of our study suggest that undergoing a complete resection, having a tumor size of 30mm or less and having no mediastinal lymph node metastases were better prognostic factors for surgically treated patients with ipsilateral pulmonary metastasis of non-small cell lung cancer.     

Bacterial superantigen enhances cytokine production by T-helper lymphocyte subset-2 cells and modifies glomerular lesions in experimental immunoglobulin a nephropathy

Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin excretion in urine, immunoglobulin concentration, and lymphokine production in vitro, as well as analysis of T-cell receptor expression in splenic T-cell subsets and examination of renal histology by light and fluorescence microscopy. Results At 40 weeks of age, the serum level of IgA in these mice was substantially increased and the number of Vβ8⁺ CD4⁺splenic T-cells was significantly decreased compared with measurements in untreated controls. Both control and SEB-treated mice excreted less than 30 μg/mL of urinary albumin. In mice given SEB, the amount of interleukin 2 (IL-2) and tumor necrosis factor-α (T helper 1 [Th1]-type cytokines) produced by the in vitro-stimulated lymphocytes significantly decreased. whereas that of interleukin 4 (IL-4) and interleukin 6 (IL-6) (Th2-type cytokines) markedly increased compared with measurements in control mice. At 40 weeks of age, mice given SEB showed marked glomerular hypercellularity and enhanced glomerular C3 deposition by renal histology, compared with control mice. Conclusion These results suggest that bacterial superantigen SEB may modify glomerular lesions through activating Th2 cells, while inducing deletion of Th1 cells in this experimental model.     

Thalamic projections to the second and fourth somesthetic areas in the anterior ectosylvian gyrus of the cat

The topical organization of thalamic projections to the second and fourth somesthetic areas in the anterior ectosylvian gyrus of the cat has been studied using the technique of retrograde axonal transport of horseradish peroxidase. The projections of the posterolateral and posteromedial ventral nuclei (VPL, VPM) to the second somesthetic area (SII) are organized somatotopically. The posterior portion of SII (hindlimb area) receives fibers mainly from the dorsolateral part of VPL, the middle portion of SII (forelimb area) from the ventromedial part of VPL, and the anterior portion of SII (face area) from VPM. These topical projections are more loosely organized and less densely arranged than those to the first somesthetic area. The SII receives a few fibers from the medial geniculate nucleus, particularly its magnocellular and dorsal principal parts, and from the suprageniculate nucleus. The posterior part of SII lying near the secondary auditory area receives many fibers from the medial geniculate and suprageniculate nuclei, and only a few fibers from the lateral central and paracentral nuclei. The fourth somesthetic area (SIV), located in the dorsal bank of the anterior ectosylvian sulcus, receives fibers mainly from the dorsal principal and magnocellular parts of the medial geniculate nucleus, and from the suprageniculate nucleus. The SIV receives a fair number of fibers from VPL and VPM roughly in a somatotopical manner. The posterior portion of SIV receives fibers chiefly from the dorsolateral part of VPL, the middle portion of SIV from the ventromedial part of VPL, and the anterior portion from VPM. In addition, SIV receives a few fibers from the lateral central, paracentral, ventral lateral and ventral medial nuclei. The SIV, together with the most posterior part of SII, forms an auditory area, receiving many fibers from the medial geniculate and suprageniculate nuclei, and a few fibers from the intralaminar nuclei.     

Distribution of homing protein on hemopoietic stromal and progenitor cells.

Homing receptor is a membrane lectin of 110 kd molecular weight that recognizes galactosyl and mannosyl residues of an as yet unknown glycoconjugate. It is responsible for recognition and selective homing of hemopoietic progenitor cells after these cells are transplanted intravenously. Consequently, it is present on the surface of hemopoietic progenitor cells. To determine the distribution of this receptor on other cell types we performed standard binding assays in many cell types using galactosyl and mannosyl residues covalently bound to bovine serum albumin (G-BSA and M-BSA) as an index of homing receptor. BSA moiety was then labeled with 125I. The three cloned hemopoietic cell lines B6Sut, FDCP-1, and FDCP-mix all showed combined binding of G-BSA and M-BSA, whereas the lymphoid cell line L1210 showed only M-BSA, not G-BSA binding and, therefore, was considered to lack homing receptors. Similarly, stromal cell lines D2X and GB1/6 as well as primary marrow stroma (progenitor cell-depleted) did not show homing receptors as evidenced by combined binding of G-BSA and M-BSA. Nor did the nonhemopoietic stromal cell line Swiss 3T3 show the presence of homing receptors by these criteria. We conclude that homing receptors are distributed narrowly and are present on hemopoietic progenitor cells, but absent on hemopoietic stroma.     

Analysis of T Cell Receptor Variability in Fresh Tumor-infiltrating Lymphocytes from Human Head and Neck Cancer

In this study, we analyzed T cell receptor (TCR) gene rearrangements in tumor-infiltrating lymphocytes (TIL) freshly obtained from 15 patients with head and neck cancer using the reversely transcribed polymerase chain reaction (RT-PCR) method. These TILs showed preferential expression of Vα10, Vα8 and Vα1, detected in 13 (87%), 11 (73%), and 9 cases (60%), respectively. The TCRVβ gene revealed diversity without preferential usage. The head and neck region is exposed to bacteria and viruses, so it is possible that the tumor site can become infected and accumulate T cells involved in infection and inflammation. Therefore, we also investigated TCR gene usage in T cells infiltrating in chronic sinusitis mucosa to address the question of whether the Vα1, Vα8, and Vα10 subfamilies are characteristic in TIL from squamous cell carcinoma of head and neck. TCR Vα10 gene usage was also the most common in Vα segment in T cells infiltrating the sinus mucosa, but Vα and Vα8 were not detected in the T cells in sinusitis. These results indicate that the Vα10 subfamily, the preferred T cell population in both TIL and T cells in inflammatory disease, might he involved mainly in inflammation or infection. On the other hand, Vα1 and Vα8 appear to be relatively specific populations for antitumor immunity in head and neck cancer.     

Studies on pyridonecarboxylic acids. 1. Synthesis and antibacterial evaluation of 7-substituted-6-halo-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3- carboxylic acids.

A series of [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids and their esters were prepared and evaluated for antibacterial activity. The derivatives with a hydrogen or methyl group at C-1, fluorine at C-6, and piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity. Compound 29a (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract. Compound 29ee (NM441), an N-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl] derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.