Modification of the damping rate of the oscillations of a dust particle levitating in a plasma due to the delayed charging effect.

Dependence of the damping rate of the oscillations of the dust particles levitating in the sheath on the plasma parameters is investigated both theoretically and experimentally. Significant deviations of the damping rate from the values predicted by the Epstein formula are found in the experiment. The delayed charging effect is applied for the theoretical explanation of the experimental results. Qualitative agreement between the theoretical and experimental data is obtained.

Eritoran inhibits S100A8-mediated TLR4/MD-2 activation and tumor growth by changing the immune microenvironment.

S100A8/A9 is a major component of the acute phase of inflammation, and appears to regulate cell proliferation, redox regulation and chemotaxis. We previously reported that S100A8/S100A9 are upregulated in the premetastatic lung. However, the detailed mechanisms by which S100A8 contributes to tumor progression have not been elucidated. In this study, we investigated the TLR4/MD-2 dependency by S100A8 on tumor progression. We found that S100A8 (2-89) peptide stimulated cell migration in a manner dependent on TLR4, MD-2 and MyD88. The S100A8 (2-89) peptide also activated p38 and NF-κB in TLR4-dependent manner. The peptide induced the upregulation of both IL-6 and Ccl2 in peritoneal macrophages obtained from wild-type mice, but not TLR4-deficient mice. We then investigated the responsible region of S100A8 for TLR4/MD-2 binding by a binding assay, and found that C-terminal region of S100A8 binds to TLR4/MD-2 complex. To further evaluate the TLR4 dependency on tumor microenvironment, Lewis lung carcinoma-bearing mice were treated with Eritoran, an antagonist of TLR4/MD-2 complex. We found that both tumor volume and pulmonary recruitment of myeloid-derived suppressor cells were reduced with the treatment of Eritoran for five consecutive days. Eritoran reduced the development of tumor vasculature, and increased tumor-infiltration of CD8(+) T-cells. Taken together, S100A8 appears to play a crucial role in the activation of the TLR4/MD-2 pathway and the promotion of a tumor growth-enhancing immune microenvironment.

Induction of effective antitumor immune responses in a mouse bladder tumor model by using DNA of an alpha antigen from mycobacteria.

One of the main objectives of cancer immunotherapy is the activation and increase in number of antitumor effector cells. Recently, genetically modified tumor cell vaccines have been proposed for elicitation of antitumor effector cells. Native alpha antigen (alpha Ag) (also known as MPT59 and antigen 85B) of mycobacteria, which cross-reacts among mycobacteria species, may play an important biological role in host-pathogen interaction because it elicits various helper T-cell type 1 immune responses. To assess the induction of antitumor immune responses by alpha Ag, mouse tumor cell lines transfected with cDNA of alpha Ag from Mycobacterium kansasii were established, and the possibility of producing a tumor cell vaccine for induction of antitumor effects was explored. Transfection of tumor cell lines with an alpha Ag gene lead to primary tumor rejection and the establishment of protective immunity to nontransfected original tumor cell lines in Mycobacterium bovis bacillus Calmette-Gurin (BCG)-primed and unprimed mice. Mice immunized with tumor cell lines transfected with the alpha Ag gene showed delayed-type hypersensitivity responses in vivo and proliferative responses together with induction of interferon-gamma of spleen cells against nontransfected wild-type tumor cell lines in in vitro experiments. Moreover, immunization of mice with alpha Ag-expressing tumor cells elicited tumor-specific and cytotoxic T lymphocyte (CTL) epitope peptide-specific CD8+ CTLs. The results of this study provided evidence of the potential usefulness of alpha Ag in tumor cell vaccines.

Induction of an eosinophil chemotactic factor production from T lymphocytes by a B cell lymphoma line.

Production of an eosinophil chemotactic factor (ECF) from human mononuclear leukocytes (MNL) was induced by coculture with an irradiated B cell lymphoma line, BALL-1. BALL-1 induced ECF production from OKT4-positive T lymphocytes without evident IL-2 production. Treatment of MNL with anti-IL-2 antibody failed to suppress the BALL-1-induced ECF production, whereas the treatment strongly inhibited IL-2-induced ECF production. Control supernatants of BALL-1 cells alone did not induce ECF production. BALL-1 fixed with periodate-lysine-paraformaldehyde, but not acetone or ethanol, induced evident ECF production. The isoelectric point of BALL-1-induced ECF (m.w. 10-30 kD) was around pI 7, whereas that of the IL-2-induced ECF was around pI 5. A combination of monoclonal antibodies against IL-3, IL-5, and GM-CSF suppressed the activity of the IL-2-induced ECF but not that of the BALL-1-induced ECF. BALL-1-induced ECF suppressed a respiratory burst from an eosinophilic cell line (YY-1) induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine, whereas the IL-2-induced ECF did not, suggesting that the biological function of these two ECF is different, at least in the effect on respiratory burst of eosinophils. From the present results we propose that one reason for infiltration of eosinophils into the stroma of tumors is that some tumor cells can stimulate OKT4-positive T lymphocytes to produce an ECF, and that eosinophils attracted by this ECF exhibit biological functions which are different from those of eosinophils attracted by other ECF.

Sexual difference and organ specificity of the effect of estradiol on carbonic anhydrase and Mg(2+)-HCO3(-)-ATPase activities isolated from duodenal mucosa and kidney cortex of male and female rats: preliminary study with crude enzyme samples.

Effects of the s.c. administration of various doses of estradiol propionate (E.P.; 25-500 micrograms/kg) on the activities of carbonic anhydrase (CA), Mg(2+)-dependent ATPase and Mg(2+)-dependent, HCO3(-)-stimulated ATPase (Mg(2+)-HCO3(-)-ATPase) in rat duodenal mucosa and kidney cortex, and on body weight, organ weight and serum concentrations of testosterone and estradiol-17 beta, were examined in adult male, female, testectomized and ovariectomized rats. In normal male rats, activities of cytosol CA and brush border Mg(2+)-HCO3(-)-ATPase in the kidney were increased in a dose-dependent manner and reached 1.6- and 2-fold of controls, respectively, after consecutive administration (daily for 7 days) of 500 micrograms E.P. with no changes in either enzyme activities in duodenal mucosa. The positive correlations (P less than 0.01) were observed by linear regression analysis between serum concentration of estradiol-17 beta and kidney cytosol CA or kidney brush border Mg(2+)-HCO3(-)-ATPase activities. In normal female rats, activities of cytosol CA and brush border Mg(2+)-HCO3(-)-ATPase in the duodenal mucosa, and brush border Mg(2+)-HCO3(-)-ATPase activity in the kidney were increased by E.P. administration (100 and 500 micrograms/kg, daily for 7 days), however, kidney cytosol CA activity did not change by any dosage. Behavior of a part of both enzymes to E.P. in testectomized rats was altered almost in the same way to that observed in normal female rats and vice versa in ovariectomized rats. Body weight was decreased, in general, by consecutive administration of E.P. in a dose-dependent manner, and kidney weight was increased by E.P. in both male and female rats.

Syringomyelia and syringobulbia associated with an ependymoma of the cauda equina involving the conus medullaris: case report.

A patient with syringomyelia and syringobulbia secondary to an asymptomatic ependymoma of the cauda equina involving the conus medullaris is described. Delayed metrizamide computed tomography myelography was decisive for making the diagnosis of a highly extended syrinx associated with the tumor. Syringomyelic symptoms improved remarkably following the removal of the tumor, and the syrinx was not visualized in a postoperative study. The pathogenesis of syringomyelia associated with a caudally located spinal cord tumor is discussed.

Treatment of intracranial nongerminomatous malignant germ cell tumors producing alpha-fetoprotein.

We treated 10 patients with intracranial nongerminomatous malignant germ cell tumors producing alpha-fetoprotein between 1969 and 1992. Two patients were treated with radiotherapy (RT) only (RT group), and three were treated with RT and cisplatin plus vinblastine plus bleomycin therapy with or without surgery (cisplatin plus vinblastine plus bleomycin group). The most recently treated five patients received cisplatin plus etoposide (PE) therapy with or without RT and/or surgery (PE group). The level of alpha-fetoprotein in serum was elevated in all 10 patients. In the PE group, PE therapy consisted of cisplatin (20 mg/m2) and etoposide (60 mg/m2) daily for 5 days (one course) given two or three times at 4-week intervals and then once every 4 months; the patients received three to six courses (mean, 4.2 courses). In the RT group (n = 2), one patient died 3 months after diagnosis and the other died at 12 months. In the cisplatin plus vinblastine plus bleomycin group (n = 3), complete remission was obtained in one patient, but the other two patients died 12 and 24 months after diagnosis. In contrast, in the PE group (n = 5), complete remission was obtained in all patients who are all currently alive without recurrence, at 35 to 71 months (average, 53.6 mo) after diagnosis. The results indicate that multidisciplinary treatment including combination chemotherapy with cisplatin and etoposide with or without surgery and/or RT is highly effective in the treatment of patients with alpha-fetoprotein-producing intracranial nongerminomatous malignant germ cell tumor.

Protective effects of 2,3-dimercaptopropane-1-sulfonate on mercuric chloride-induced acute inhibition of enzymes from rat duodenal mucosa and kidney cortex.

Acute inhibitory effects of mercuric chloride on the activities of several enzymes from rat duodenal mucosa and kidney cortex and the protection provided by 2,3-dimercaptopropane-1-sulfonate (DMPS) were examined. Activities of carbonic anhydrase in homogenate, brush border and cytosol and of Mg(2+)-dependent, HCO3-stimulated ATPase in homogenate and brush border of duodenal mucosa and kidney cortex and activities of kidney microsomal Mg(2+)-dependent, Na(+)-K(+)-stimulated ATPase were all decreased following administration of HgCl2 (1-3 mg Hg/kg body weight s.c. once daily for 3 days). Decreases occurred generally in a dose-dependent manner and went back to near normal or normal levels by the combined administration of 20 and 30 mg DMPS/kg per day for 3 days. The concentration of serum urea nitrogen was increased about 8 times by the administration of 2 mg Hg/kg and restored to normal by the concomitant administration of 30 mg DMPS/kg. After the administration of 2 mg Hg/kg per day for 3 days, about half of the renal cortical proximal tubuli were necrotic. Administration of 30 mg DMPS/kg restored these changes to almost normal. The results suggest that DMPS is useful in mitigating acute Hg poisoning and that part of the protective effect of DMPS on enzyme damage induced by Hg poisoning may be due to its chelating action.

Characterization of a streptococcal antitumor glycoprotein (SAGP).

An acidic antitumor glycoprotein (SAGP) was purified from a crude extract of Streptococcus pyogenes, Su strain. Intraperitoneal injection with SAGP (20 mg protein/kg/day for 4 consecutive days) prolonged the life span of mice inoculated i.p. with Ehrlich ascite carcinoma cells and methylcholanthrene-induced fibrosarcoma cells (Meth A) up to 244% and 169% of that of the control mice, respectively. These in vivo antitumor effects were reduced in immunosuppressed mice. The effector spleen cells from the Meth A-inoculated and SAGP-injected mice showed a considerable cytostatic activity on Meth A cells in vitro, and immunosuppression studies suggested that carrageenan-sensitive and/or asialo-GM1 positive spleen cells are responsible for the in vivo antitumor effect of SAGP. SAGP inhibited the cell growth of cultured cell lines including transformed hamster embryonic lung cells, murine leukemia L 1210, Meth A and human promyelocytic leukemia HL60 cells. The IC50s for the cell growth of these cells were all below 0.1 microg protein/ml. SAGP inhibited the incorporation of nucleic acid precursors into Meth A cells. It seems that sulfhydryl groups of the SAGP molecule are essential for the expression of the antitumor action of SAGP. The cell growth-inhibitory activity of SAGP was diminished in Meth A cells preincubated with pertussis toxin (IAP), whereas it was augmented in the cells preincubated with cholera toxin (CTX), suggesting the involvement of toxin-sensitive GTP (G)-proteins in the SAGP-action. IAP and CTX-catalyzed ADP ribosylation assays confirmed that SAGP augmented the activity of IAP-sensitive G-protein. In addition, this augmentation was detected neither in Meth A cells incubated with heat-inactivated SAGP nor in SAGP-insensitive L929 cells. SAGP induced apoptosis in Meth A and HL60 cells as assessed by DNA fragmentation. A single dose injection of SAGP (100 mg protein/kg, i.v., s.c., or i.p.) into mice produced no toxic signs except occasional pain responses observed for one week after the injection. Thus, SAGP is a low toxic substance that shows in vivo antitumor activity by modulating immune responses of the host, and also exhibits in vitro cell-growth inhibition through IAP-sensitive G-protein.

Evidence for the involvement of sulfhydryl groups in the expression of antitumor activity of streptococcal acid glycoprotein (SAGP) purified from crude extract of Streptococcus pyogenes.

An acidic glycoprotein (SAGP), purified from crude extract (CE) of Streptococcus pyogenes, inhibits the growth of murine fibrosarcoma (Meth A) cells in vitro and prolongs the life span of mice inoculated with the same cells. This study revealed that the growth inhibitory activity of SAGP on Meth A cells in vitro was lowered in the presence of sulfhydryl-oxidizing agents such as cystamine and 5, 5'-dithiobis (2-nitrobenzoic acid) in a dose dependent manner. The activity of SAGP was also diminished by pretreatment of SAGP with cystamine. Inactivation of SAGP by cystamine was reversed by dithiothreitol. Furthermore, the effect of CE on prolonging the life span of Meth A-bearing mice was reduced by the administration of cystamine. These findings suggest that SH-groups are involved in the expression of anti-tumor activity of SAGP or CE in vitro and in vivo.

Antiproliferative and apoptosis-inducing effects of an antitumor glycoprotein from Streptococcus pyogenes.

An acidic glycoprotein (SAGP) purified from an extract of Streptococcus pyogenes has been shown to inhibit the growth of methylcholanthrene-induced fibrosarcoma A (Meth A) cells via pertussis toxin-sensitive GTP-binding protein. The present study revealed that SAGP has activity to induce apoptosis in Meth A cells as assessed by DNA fragmentation and cell morphology with chromatin staining. The SAGP-induced DNA fragmentation in Meth A cells was augmented by herbimycin A, an inhibitor of protein tyrosine kinase, and prevented by orthovanadate, an inhibitor of protein tyrosine phosphatase. The growth inhibitory effect of SAGP on Meth A cells was reduced by orthovanadate, whereas the effect tended to be increased by herbimycin A. Western blotting analysis using antiphosphotyrosine antibody demonstrated that tyrosine phosphorylation of 170 kDa cellular protein was diminished in the cells incubated with SAGP. The inhibition of protein tyrosine phosphorylation was neither observed in the cells incubated with SAGP and orthovanadate nor in the cells incubated with heat-inactivated SAGP. These findings indicate that inhibition of tyrosine phosphorylation by protein tyrosine phosphatase(s) may be responsible for the SAGP-induced apoptosis and inhibition of cell growth.

Detection of Borna disease virus in a pregnant mare and her fetus.

A pregnant mare showing pyrexia, reduced appetite, ataxia and paresis was euthanized and examined for the presence of Borna disease virus (BDV). Her brain, showing multiple neuronal degeneration and necrosis with hemorrhage, and the histologically normal brain of the fetus were both positive for BDV RNA. The BDV nucleotide sequences were identical in the mare and fetus in the second open reading frame (ORF). This is the first report of the possible vertical transmission of BDV in a horse.

Disseminated Trichosporonosis with Trichosporon asahii.

Trichosporon asahii fungemia was associated with multiple, purpuric, papular lesions on the abdomen and extremities in a 53-year-old man with acute myeloblastic leukemia. Histologically, budding yeasts were demonstrated in the dermis. The yeast-form fungus was identified as T. asahii.

A simplified method for purification of an antitumor acidic glycoprotein from Streptococcus pyogenes (Su strain) by immunoadsorbent chromatography.

A simplified method for purification of an antitumor acidic glycoprotein (SAGP) from Streptococcus pyogenes (Su strain) by immunoaffinity chromatography is described. A cell-free crude extract prepared from the cocci was applied to the anti-SAGP IgG coupled Sepharose column, and elution was conducted with an alkaline buffer. The material eluted was confirmed to be homogeneous and identical with SAGP as demonstrated by both relative mobility on the SDS-polyacrylamide gel column and the antigenicity on the double diffusion agar plate. The cell-growth inhibitory activity of SAGP prepared by the present method was almost the same as that of SAGP purified by the previous time-consuming method. Since this simplified method provides a higher yield of SAGP, it will be useful in further studies on the biological properties of SAGP.

834-B1, a new thiolactone containing antibiotic taxonomy, fermentation, isolation and structure.

A new thiolactone containing antibiotic 834-B1 was isolated from the culture broth of Streptomyces sp. Y-0834H which has also produced thiolactomycin and thiotetromycin at the same time. The structure of 834-B1 was determined as I by the decoupling experiment in NMR.

Comparison of gentamicin nephrotoxicity between rats and mice.

Toxic effects of gentamicin administration (10-80 mg/kg body weight, subcutaneously (s.c.), once daily for 7 days) on several enzyme activities of kidney and duodenal mucosa together with other parameters were compared between male rats and mice. In Wistar rat kidney, tubular brush border Mg(2+)-dependent, HCO3(-)-stimulated ATPase (Mg(2+)-HCO3(-)-ATPase) activity was inhibited by 40-80 mg/kg gentamicin in an almost dose-dependent manner with no changes in microsomal Mg(2+)-Na(+)-K(+)-ATPase activity. Cytosol carbonic anhydrase (CA) activity was inhibited only by 80 mg/kg gentamicin. In rat duodenal mucosa, Mg(2+)-HCO3(-)-ATPase and CA activities were unchanged by any dose of gentamicin. Rat serum urea nitrogen (UN), GOT and GPT concentrations and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity were significantly increased by 80 mg/kg gentamicin. In ddY mice, however, almost all parameters described above were unaffected by gentamicin except for the urinary NAG activity which was increased only by 80 mg/kg gentamicin. The concentration of gentamicin in cytosol of rat whole kidney was approximately 3.4-fold higher compared with that in mouse kidney after 80 mg/kg treatment. In light microscopic analysis, 80 mg/kg gentamicin produced necrosis in the greater part of rat kidney proximal tubuli with no pathological findings in mouse kidney. In conclusion, Mg(2+)-HCO3(-)-ATPase activity in brush border membrane of rat proximal tubuli was selectively damaged in gentamicin nephrotoxicity, indicating that the rats are the suitable model for studies of gentamicin nephrotoxicity in humans.

Measurement of rat brain spectra.

A method of optically monitoring oxygen saturation of blood haemoglobin in the rat brain stem was developed. Optical fiber bundles were attached to the orifices of both ears of the rat to irradiate incident light from one ear and receive transmitted light from the other ear. Absorption spectra were measured using a white-light source and a photodiode array spectrophotometer. Stable measurements of optical time courses and absorption spectra were made using this "ear-to-ear" path. Oxygen saturation levels were calculated from spectra by using a suitable reference and an improved method of determining spectral peak heights.

[Fundamental and clinical studies on T-1982 (cefbuperazone) in the field of obstetrics and gynecology].

T-1982 (cefbuperazone), a new cephamycin antibiotic, was fundamentally and clinically studied in the field of obstetrics and gynecology. The following results were obtained. The concentrations of T-1982 in arterial and venous blood and genitalia were measured. The results demonstrated favourable transfer of drug into various internal genital organs. T-1982 was administered to 13 patients. The effectiveness rate was 92.3%, that is to say, excellent in 4 cases, good in 8 cases and poor in 1 case. As for side effect, any noteworthy effect was not observed.

[Fundamental and clinical studies on aztreonam in obstetrics and gynecology].

Fundamental and clinical studies on gynecological use of aztreonam (AZT), a new monobactam, were performed with following results. Following the intravenous administration of 1 g dose of AZT, the transfer of AZT to pelvic dead space exudate was good, in which the concentration of that was 14.9 micrograms/ml (2 hours), 15.3 micrograms/ml (3 hours) after injection. The transfer of AZT to serum of umbilical cord and amniotic fluid was excellent. In a clinical trial, AZT was given to 5 patients with obstetric and gynecological infections. The clinical efficacy was evaluated as excellent in 1 case and good in the other 4 cases. No adverse effects were observed in any of the patients treated with AZT.

[Fundamental and clinical study on cefminox in the obstetrical and gynecological field].

UNLABELLED: In order to assess clinical utility of cefminox (CMNX, MT-141), its transference into internal genital organ tissues and pelvic dead space was determined. In addition, transference of CMNX from maternal blood into fetal umbilical cord blood as well as into amniotic fluid was evaluated. In the clinical study, CMNX was administered in 4 cases. The following results were obtained. Transference into internal genital organ tissues; The concentration ratio of each tissue against serum concentration ranged from 25.3 to 42.7%, showing favourable transference as compared to other cephems. Transference into pelvic dead space; At 6 hours after intravenous injection of 1 g CMNX, its concentration in the pelvic dead space reached its peak of 38.8 micrograms/ml of the serum concentration, followed by gradual decrease. Transference into umbilical cord blood and amniotic fluid; Following intravenous injection of 1 g CMNX, its concentration in umbilical cord blood became almost similar to that of maternal blood at about 3 hours later, being 20 micrograms/ml. After that, it tended to decrease in accordance with the concentration in maternal blood. It appears that the drug persists for a more prolonged period in amniotic fluid. CLINICAL RESULTS: Clinically, CMNX was used in the treatment of 4 cases including 2 cases of lymphocystitis, 1 case of intrapelvic cellulitis and 1 case of postoperative wound abscess, and the results obtained were rated as excellent in 1 case, good in 2 cases and poor in 1 case with an efficacy rate of 75%. None of the cases treated experienced adverse reactions nor any laboratory abnormalities were observed.