Effects of emulsifying components in the continuous phase of cream on the stability of fat globules and the physical properties of whipped cream.

The emulsifying components in cream are very important in controlling the physical characteristics of whipped cream. The effects of those components on the stability of fat globules and the physical characteristics of whipped cream were investigated. A low-molecular-weight emulsifier, and protein ingredients such as sodium caseinate and a casein partial hydrolysate (casein peptides), were used as emulsifying components in this investigation. The viscosity of deaerated whipped cream (called the serum viscosity) was measured to evaluate the degree of fat-globule aggregation. Furthermore, the shape-retention ability, which is the degree of reduction in the firmness of whipped cream between immediately after whipping and after 1d of refrigeration, was explored. The addition of the low-molecular-weight emulsifier in the continuous phase of dairy cream, which does not contain added low-molecular-weight emulsifiers, increased the stability of the fat globules and reduced the shape-retention ability of the whipped cream. The addition of protein ingredients (sodium caseinate and casein peptides) to the continuous phase of dairy cream had little effect. However, the addition of casein peptide in the continuous phase of dairy cream together with the low-molecular-weight emulsifier reduced the effect of the low-molecular-weight emulsifier on the stabilization of fat globules and the shape-retention ability of the whipped cream. The addition of casein peptide did not recover the serum viscosity; thus, other mechanisms might underlie this phenomenon.

Reliability and validity of Japanese version of the McGill Quality of Life Questionnaire assessed by application in palliative care wards.

The McGill Quality of Life Questionnaire (MQOL), which consists of 16 items constructing physical, psychological, existential and support subscales and one item of overall quality of life (QOL), has been developed to assess QOL of terminal cancer patients. To examine if MQOL Japanese version (MQOL-J) is applicable, it was administered to 83 terminal cancer patients in palliative care wards several days after admission and then 7 to 10 days after the first interview. Cronbach's alpha coefficient for four subscales was 0.584-0.860. Sixteen items were classified into four factors by factor analysis, similar to the original English version. The results indicated that psychological and existential domains of the MQOL-J significantly related to overall QOL. Existential and support domains as well as overall QOL were significantly improved between the first and second interviews, although performance status assessed by Eastern Cooperative Oncology Group worsened. It is suggested that MQOL-J can reflect perceived health status of terminal cancer patients.

Polyglutamation of antifolates is not required for induction of extracellular release of adenosine or expression of their anti-inflammatory effects.

Methotrexate (MTX) exerts an anti-inflammatory effect, reportedly by enhancing the release of adenosine, through an accumulation of 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR). To examine the role of polyglutamation in promoting anti-inflammatory effects by antifolates, we tested whether a new antifolate designed to be resistant to intracellular polyglutamation (MX-68) exhibited anti-inflammatory effects and stimulated adenosine release. Both MX-68 and MTX (at concentrations greater than 0.1 microM) increased the release of adenosine from Daudi cells in vitro. Inhibition of AICAR synthesis suppressed adenosine release by MX-68 and MTX. The anti-inflammatory effects of antifolates were estimated using the murine air pouch model, in which a BALB/c mouse was intraperitoneally injected with MX-68 or MTX once a week for 3 weeks. MX-68 (0.5 mg kg(-1) week(-1)), as well as MTX, inhibited infiltration of leukocytes into the air pouch. This inhibitory effect was suppressed in the presence of an adenosine A(2) receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX). These results suggest that MX-68, like MTX, exerts anti-inflammatory effects through the accumulation of AICAR and release of adenosine. These results suggest that polyglutamation of antifolate is not required for expression of anti-inflammatory effects.

Oolong tea polyphenol extract induces apoptosis in human stomach cancer cells.

The exposure of human stomach cancer KATO III cells to oolong tea polyphenol extact [OTPE] containing oolong tea polyphenol trimer [OTP trimer] as a main component, led to both growth inhibition and the induction of apoptosis. Morphological change showing apoptotic bodies was observed in the cells treated with OTPE. The fragmentation by OTPE of DNA to oligonucleosomalsized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. These data suggest that the growth inhibition by OTPE results from the induction of apoptosis in the KATO III cells.

A novel antifolate, MX-68, inhibits the development of autoimmune disease in MRL/lpr mice.

We compared a novel unpolyglutamable antifolate, MX-68, with polyglutamable antifolate, methotrexate (MTX), for treatment of an autoimmune kidney disease which develops spontaneously in MRL/Mp-lpr/lpr (MRL/lpr) mice. Oral administration of either MX-68 or MTX was commenced in 8-week-old female mice and continued 3 times a week until they reached 30 weeks of age. MX-68 delayed the onset of proteinuria and prolonged life span dose-dependently. Furthermore, it suppressed the elevation of serum blood urea nitrogen and cholesterol levels. MX-68 was as effective as MTX at ameliorating events which accompany the development of lupus nephritis, despite that MX-68 did not undergo polyglutamation. These ameliorative effects of MX-68 and MTX did not occur via inhibition of either autoantibody production or cell proliferation. Neither compound suppressed age-dependent elevation of immune complexes or antibodies for single-stranded DNA and TNP in serum nor did they influence the associated enlargement of lymph nodes and spleen. We conclude that MX-68 is beneficial for the treatment of autoimmune kidney disease in mice and may be useful for other related diseases such as systemic lupus erythematosus.

Preventive effect of a novel antifolate, MX-68, in murine systemic lupus erythematosus (SLE).

We evaluated the preventive effects of a novel nonpolyglutamatable antifolate, MX-68, on two experimental murine models of systemic lupus erythematosus (SLE); NZBxNZW F1 (BWF1) mice and chronic graft-versus-host disease (GVHD) mice, in comparison with classical antifolate methotrexate (MTX). The oral administration of 2 mg/kg MX-68, three times a week from 12 to 40 or 60 weeks of age, significantly delayed the onset of proteinuria and prolonged the life-span of BWF1 mice. The elevation of serum blood urea nitrogen (BUN) and cholesterol levels resulting from the development of lupus nephritis was also inhibited. However, MX-68 did not suppress the increase of serum anti-DNA or anti-TNP antibodies or total IgG isotype (IgG1, IgG2 and IgG3) levels. In chronic GVHD mice, MX-68 given three times a week from the day of first cell injection, for 9 weeks, dose-dependently delayed the appearance of proteinuria. The elevation of BUN and cholesterol levels was also inhibited. Furthermore, in the 4 mg/kg MX-68 group, the production of IgG anti-DNA and anti-TNP antibodies was significantly inhibited, but this was not observed in the 2 mg/kg MX-68 and the 4 mg/kg MTX groups. These beneficial effects of MX-68 were much greater than those of MTX in both models. These results suggest that MX-68 might be a more useful drug for the treatment of SLE.

In vitro and in vivo biological activities of a novel nonpolyglutamable anti-folate, MX-68.

MX-68 is a newly synthesized anti-folate, chemically designed not to undergo intracellular polyglutamation and to have increased affinity to dihydrofolate reductase (DHFR). In the present study, we examined the in vitro and in vivo biological activities of MX-68 compared with methotrexate (MTX) which forms several polyglutamates intracellularly. MX-68 dose-dependently inhibited the proliferation of PHA-, anti-CD3-, or PMA plus ionomycin-stimulated peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) from normal subjects as well as IL-1 beta- or TNF alpha-stimulated synovial fibroblastic cells (SC) from rheumatoid arthritis (RA) patients. Coaddition of folinic acid completely reversed the anti-proliferative effects of both MX-68 and MTX. Although the anti-proliferative activities of MX-68 were almost comparable to those of MTX, the washout study clearly showed the characteristic nature of MX-68. When drugs were removed during culture, the suppressive effect of MX-68 completely disappeared, whereas suppression by MTX was merely weakened. MX-68 dramatically suppressed the onset of collagen-induced arthritis (CIA) in mice when the drug was orally administered three times a week. starting from the day of first immunization. In this model, 2 mg/kg of MX-68 was sufficient to completely suppress arthritis, whereas suppression by the same dose of MTX was partial. These lines of evidence suggest that polyglutamation is not always a prerequisite in the anti-rheumatic effects of anti-folate. In addition, since intracellular accumulation of polyglutamates is thought to have adverse effects, MX-68 may become a more potent and less toxic anti-rheumatic drug than MTX.

Separating the effects of alertness from the effects of encoding in a pitch-imagery task.

The facilitatory effects of auditory imagery have often been attributed to priming. However, the facilitatory effects of a prime on subsequent processing can be separated into effects related to specific perceptual processes, such as encoding, and effects related to more general processes, such as alertness. Whereas research on auditory imagery has focused on code-activated facilitation, the role of alertness in image-induced facilitation has been largely presumed rather than empirically investigated. Therefore, a study was designed to isolate the facilitatory effects of alertness from those of encoding. The results show that the nonspecific alerting effects of auditory imaging were quite extensive--a nearly 78-ms decrease in reaction time--compared with the effects of encoding.

Transcriptional activation of c-fos and c-jun protooncogenes by serum growth factors in osteoblast-like MC3T3-E1 cells.

The present study was undertaken to clarify the relationship between c-fos and c-jun protooncogene expression and the differentiation and/or proliferation of osteoblasts, using osteoblast-like MC3T3-E1 (E1) cells. c-fos mRNA was barely detectable, whereas c-jun mRNA was constitutively expressed in E1 cells after serum deprivation for 24-72 h. When serum was added, a rapid and transient induction of c-fos and c-jun mRNAs was observed. The c-fos and c-jun mRNAs reached peak levels at 30 minutes, with a rapid disappearance of c-fos mRNA within 3 h and a much slower decrease in c-jun mRNA. The addition of serum together with cycloheximide, an inhibitor of protein synthesis, resulted in the superinduction of both c-fos and c-jun mRNAs. Among various growth factors, PDGF, EGF, and bFGF mimicked the serum effect, whereas IGF-I and TGF-beta failed to induce c-fos and c-jun mRNA. The effects of PDGF, EGF, and bFGF were completely abolished by pretreatment with actinomycin D, an inhibitor of RNA synthesis, suggesting a transcriptional mechanism. Nuclear runoff experiments showed that the transcription rate of c-fos and c-jun protooncogenes was increased by serum and growth factors. The effects of PDGF, EGF, and bFGF were inhibited by H-7 or staurosporine, inhibitors of protein kinase C (PKC), but not by HA1004 with a much weaker inhibitory activity, suggesting the involvement of PKC for the activation of the protooncogenes.(ABSTRACT TRUNCATED AT 250 WORDS)

Lobenzarit disodium (CCA) inhibits in vitro immunoglobulin production via direct interaction with B lymphocytes.

The regulatory effects of lobenzarit disodium (CCA), a therapeutic agent for treating rheumatoid arthritis (RA), on polyclonal immunoglobulin production by human lymphocytes were investigated in vitro. CCA inhibited the production of immunoglobulin in all the classes examined at a clinically relevant concentration. Moreover, it inhibited the immunoglobulin production as well as lymphocyte proliferation even when purified B lymphocytes preactivated by Staphylococcus aureus COWAN I were cultured with recombinant lymphokines such as IL2 and IL6. These results suggest that CCA acts directly on B lymphocytes. The analysis at each of two different stages of B lymphocyte activation lineage, i.e., the primary activation stage and a stage of proliferation and differentiation to antibody secreting cells, has indicated that CCA inhibits the proliferation-differentiation stage of B lymphocytes. CCA does not inhibit B lymphocytes at the primary activation stage; actually, it augments them, resulting in the subsequent enhancement of immunoglobulin production.

Overexpression of src family gene for tyrosine-kinase p59fyn in CD4-CD8- T cells of mice with a lymphoproliferative disorder.

Overexpression of a src family gene, lck, has been associated with differentiation of the murine thymic lymphoma line LSTRA. Recent findings by several groups strongly suggest a functional role for the gene product p56lck protein-tyrosine kinase (PTK) in the activation of normal T cells. A single recessive gene, lpr or gld, induces a lymphoproliferative disorder concomitant with autoimmune disease in mice. In this study, a 10-fold elevated activity of PTK encoded by fyn, another src family gene, was demonstrated in CD4-CD8- T cells in mutant mice. The increased PTK activity was consistent with overexpression of fyn mRNA. The elevated fyn mRNA expression appeared to be a characteristic of CD4-CD8- T cells, since it was not observed in normal T cells at any stage of differentiation. The fact that fyn mRNA expression was markedly induced in normal T cells by mitogenic stimulation with anti-T3 epsilon antiserum supports the possibility that p59fyn PTK is a signal-generating molecule in T cells. Thus, our findings provide insight into the physiological role for a src gene family kinase in T-cell development and contribute to a better understanding of the molecular mechanisms of disease-inducing recessive genes.