Interleukin-4 as a potent down-regulator for human alveolar macrophages capable of producing tumour necrosis factor-alpha and interleukin-1.

The effects of recombinant human interleukin-4 (IL-4) on the production of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) by human alveolar macrophages (AM) and autologous peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) were examined. AM and PBM were obtained by bronchoalveolar lavage and centrifugal elutriation, respectively, from healthy donors. The production of IL-1 (alpha and beta) and TNF alpha by human AM and PBM were quantitated by enzyme immunoassays (EIA). When activated with LPS, AM secreted much more TNF alpha, but less IL-1 beta than PBM. The production of IL-1 (alpha and beta) by activated AM and autologous PBM was suppressed dose-dependently by IL-4. The inhibitory effect of IL-4 was greatest when it was added to AM or PBM simultaneously with LPS or within 3 h after LPS. The suppressive effect of IL-4 was completely neutralized by pretreatment with rabbit anti-IL-4 antiserum. IL-4 also suppressed the production of IL-1 and TNF alpha by monocyte-derived macrophages. As measured by thymocyte co-stimulation assay, the production of cell-associated IL-1 was inhibited by coculture of AM plus LPS with IL-4. Northern blot analysis showed suppression by IL-4 of expression of messenger ribonucleic acid (mRNA) for IL-1 and TNF alpha in LPS-stimulated AM. We conclude that IL-4 is a potent down-regulator for human alveolar macrophages capable of producing IL-1 and TNF alpha.     

Effect of gastrointestinal maturation on absorption of beta-lactam antibiotics.

Gastrointestinal absorption of cefazolin, which is poorly absorbed in adults, and of cephradine, which is well absorbed in adults, was studied in rats during their development. Significantly higher concentrations of cefazolin in plasma after oral administration were observed in 1- and 2-week-old rats compared with 3-week-old and adult rats. A marked difference in the absorption of cefazolin by 2- and 3-week-old rats (at weaning period) was observed. No such marked difference in the absorption of cephradine by rats of various age groups was found. With cefazolin, a similar pattern of developmental change in jejunal uptake was observed. Cortisone, which causes early maturation of the intestinal membrane, was given as a preweaning injection to 2-week-old rats. This treatment decreased concentrations of cefazolin in plasma and jejunal uptake of cefazolin. Thus, the absorption of cefazolin in 1- and 2-week-old rats seems to depend on the permeability of the immature intestinal membrane before weaning. Cephradine absorption from the intestine of 1-week-old rats became saturated and inhibited by carnosine and glycylglycine when studied by the in situ loop method. Cefazolin absorption was proportional to luminally administered doses and was not affected by carnosine and glycylglycine. A nonsaturable process for cefazolin and a saturable process for cephradine were also observed in an in vitro uptake experiment.     

Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer.

PURPOSE: To evaluate the treatment results of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (ISBT) for T3 mobile tongue cancer. MATERIAL AND METHODS: Between 1974 and 1992, 61 patients with T3 mobile tongue cancer were treated with LDR ISBT using (192)Ir hairpins with or without single pins. In addition, between 1991 and 1999, 14 patients were treated with HDR ISBT. For nine patients treated with ISBT alone, the total dose was 59-94 Gy (median 72 Gy) within one week in LDR ISBT and 60 Gy/10 fractions/5 days in HDR ISBT. For 66 patients treated with a combination therapy of external beam radiotherapy (EBRT) and ISBT, the total dose was 12.5-60 Gy (median 30 Gy) of EBRT and 50-112 Gy (median 68 Gy) within 1 week in LDR ISBT or 32-60 Gy (median 48 Gy)/8-10 fractions/5-7 days in HDR ISBT. RESULTS: The 2- and 3-year local control rates of all patients were both 68%. The 2- and 3-year local control rates of patients treated with LDR ISBT were both 67%, and those with HDR ISBT were both 71%. The local control rate of patients treated with HDR ISBT was similar to those with LDR ISBT. CONCLUSIONS: ISBT for T3 mobile tongue cancer is effective and acceptable. The treatment result of HDR ISBT is almost similar to that of LDR ISBT for T3 mobile tongue cancer.     

Glial localization of four‐repeat tau in atypical progressive supranuclear palsy

In the present case, a patient in whom limb apraxia and asymmetrical parkinsonism developed suggesting corticobasal degeneration, is reported. Neuropathologic examination revealed numerous tufted astrocytes in the precentral cortex in addition to the characteristic pathologic findings of PSP. Therefore, on the basis of clinicopathologic features, atypical progressive supranuclear palsy was diagnosed. In addition, the brain tissue of the present patient was investigated with an antibody specific for four‐repeat tau (4R‐tau). In the precentral cortex, numerous tau‐positive tufted astrocytes, pretangles, and threads were positive for 4R‐tau. Using a confocal microscopy we demonstrated that tufted astrocytes positive for 4R‐tau were adjacent to astrocytes positive for GFAP. The present findings suggest that accumulation of four‐repeat tau in astrocytes is a degenerative process rather than a reactive process.     

Immunoreactive opsin and glial fibrillary acidic protein in persistent hyperplastic primary vitreous

An 8-month-old boy had an anterior type of persistent hyperplastic primary vitreous in the right eye. Results of needle biopsy, performed because of elevated intraocular pressure, disclosed clusters of blastic cells. The eye was enucleated on the suspicion of retinoblastoma. Histological examination showed retrolental fibrovascular tissue and retinal dysplasia. Immunoreactive opsin was detected in the innermost structures and in photoreceptor-like cells of rosettes. We conclude that photoreceptor cells differentiated to express opsin, even when neighbouring cells were abnormally arranged. An immunocytochemical study of glial fibrillary acidic protein demonstrated glial proliferation in the inner layer of the retina but not in the preretinal space.     

Virucidal activity and viral protein modification by myeloperoxidase: a candidate for defense factor of human polymorphonuclear leukocytes against influenza virus infection.

Influenza virus (IFV) was inactivated by treatment with degranulated fluid (DF) or myeloperoxidase (MPO) from human polymorphonuclear leukocytes in the presence of H2O2. Hemagglutinin and neuraminidase activities of the virus were also reduced by DF treatment. In addition, treatment with DF or MPO in the presence of H2O2 resulted in delayed migration of viral proteins in SDS-PAGE, indicating extensively modified viral proteins. Parallel with this aberrant migration, the radioactivity of each protein band on SDS-PAGE using [35S]methionine-labeled IFV was greatly reduced. Moreover, some of the modified viral protein did not migrate. A small amount of acid-soluble degraded viral peptide was also generated. The modification of the proteins was exhibited in all major viral proteins, including the inner proteins in the envelope. These results suggest that inactivation of IFV and protein modification by DF is due to MPO present in DF.     

The determination of thymidylate synthetase inhibition for testing fluoropyrimidines--pharmacokinetics and metabolism of carmofur (HCFU) in patients with gynecologic malignancies--Tokai HCFU Study Group for Gynecologic Malignancies

The pharmacokinetics and metabolism of carmofur (HCFU) were studied. Sixty-six patients were administered 100 mg of HCFU orally, and the plasma levels of the HCFU fraction (HCFUf) and 5-fluorouracil (5-FUra) were determined at 0, 1, 2, 4 and 6 hours. The average half-life of HCFUf and 5-FUra were 1.05 and 1.31 hours, and the average areas under the curves (AUC) of the plasma concentration were 6.51 hr X mcg/ml and 0.46 hr X mcg/ml, respectively. Surgical specimens of the tumors were obtained about three hours after the administration and assayed for HCFUf. 5-FUra fluorodeoxyuridine-monophosphate (FdUMP), deoxyuridine-monophosphate (dUMP), total thymidylate synthetase (TS total), and non-FdUMP-bound free enzyme (TS free). The TS inhibition rate (IR) was calculated by the follow method: IR = (TS total-TS free)/TS total X 100 levels of the TS total varied from not-detected (less than 0.10 pmol/g) to 20.5 pmol/g. The average FdUMP: dUMP ratio was 3.44 X 10(3), However, more than 80% inhibitions of TS were observed in nine cases (21.4%). The correlation indicates between TS IR and tissue FdUMP level or FdUMP: dUMP ratio were 0.57 and 0.62 in ovarian malignancies respectively. No significant correlations were observed between TS inhibition and levels of tissue 5-FUra or AUC of 5-FUra.     

A study of revised self-monitoring scale]

The present study attempted to construct the Japanese version of Revised Self-Monitoring Scale (Lennox & Wolfe, 1984). Factor analysis of this scale yielded two factors: 1) Sensitivity to expressive behavior of others, 2) Ability to modify self-presentation. This scale and its two factors had acceptable internal consistency: these results were almost similar with the original study. In correlational analyses with other personality measures, this scale correlated positively with both Private and Public Self-Consciousness Scale and Maudsley Personality Inventory-E Scale, but positively or negatively with some scales of Yatabe-Guilford Personality Inventory (e.g., G, S: positively. I, T: negatively.). Moreover the correlations between the two factors and the above mentioned measures provided interesting results. The availability of this scale was discussed.