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6- O - Acylated l -ascorbic acids possessing a straight- or branched-acyl chain of varying length from C 4 to C 18 have been synthesized and evaluated their anti-tumor promoting effects on the activation of the Epstein–Barr virus early antigen. The derivatives having a straight- or branched-acyl chain of C 6 to C 11 carbon atoms exhibited marked effects.

An immunopotentiator obtained from Chlorella vulgaris strain CK22, showed antitumour effects against various lines of syngeneic tumours, especially by intratumour administration. The immunopotentiator exhibited far greater antitumour activity against a rechallenged tumour than against the primary-inoculated tumour in Meth A and BALB/c or CDF1 mouse systems. The antitumour effect was at least comparable to that of a streptococcal preparation, OK-432, which has been widely used for clinical immunotherapy. The active compound was fractionated by anion-exchange and affinity chromatography monitoring by the Meth A rechallenge system. The most active fraction, Q2C2, consisted of galactose-rich carbohydrate (56.1%) and protein (36.3%). Antitumour activity disappeared after protease digestion, but was stable for extreme treatments of acid, alkali, heat and carbohydrate degradation. These facts indicate that the protein moiety of the glycoprotein is mainly related to express the antitumour activity. © 1998 John Wiley & Sons, Ltd.

A glycoprotein extract (CVS), derived from the unicellular green alga Chlorella vulgaris, strain CK22, exhibited a pronounced antitumor effect against both spontaneous and experimentally induced metastasis in mice. Inhibition of tumor metastasis was enhanced when intratumor administration of CVS was followed by s.c. injection of CVS. Anti-metastatic immunopotentiation was observed in euthymic mice, but not in athymic nude mice. The antitumor activity of CVS was reflected in antigen-specific, T-cell-mediated immunity. Both CD4 and CD8 T cells contributed to the antimetastatic effects, as shown by in vivo depletion experiments with anti-T-cell subset antibodies. Furthermore, CVS caused the recruitment of T cells to the regional lymph nodes and their proliferation in these organs. The CD4-positive population, following CVS injection at the time of tumor rechallenge, displayed a pronounced increase in the proportion of T cells that were CD18 bright, CD44 bright, CD25+, CD54+, CD69+ or CD71+ in the lymph nodes. Thus, CVS induces T cell activation in peripheral lymph nodes in tumor-bearing mice. We conclude that CVS augments antimetastatic immunity through T cell activation in lymphoid organs and enhances recruitment of these cells to the tumor sites. Presurgical treatment with CVS might prevent metastasis or tumor progression.

We have previously reported that oral administration of hot water extract of Chlorella vulgaris (CVE) enhances resistance to Listeria monocytogenes through augmentation of Listeria -specific cell-mediated immunity in normal mice and mice with murine acquired immunodeficiency syndrome (MAIDS) caused by murine leukemia virus (MuLV) LP-BM5 . To elucidate the mechanisms whereby CVE augments the cell-mediated immunity, we examined the expression patterns of mRNA for cytokines in normal and MAIDS mice given CVE orally after L. monocytogenes infection. The expression levels of IL-1α, IL-12, GM-CSF, MIP and TNFα genes were significantly augmented in the peritoneal adherent cells by oral administration of CVE for 2 weeks before Listeria infection. The expression levels of γIFN and IL-12 mRNA were significantly higher in the spleen after Listeria infection in CVE-treated mice than in normal mice, while the expression of IL-10 mRNA in the spleen was decreased by CVE administration. In MAIDS mice, oral administration of CVE also augmented the expression of γIFN and IL-12 mRNA in the spleen after Listeria infection, while it rather reduced the expression of IL-10 mRNA. These results suggest that CVE may preferentially augment Th1 responses against Listeria via activation of macrophages to produce IL-12 and enhance host defense against Listeria infection both in normal and MAIDS mice.

An acidic glycoprotein prepared from a culture of Chlorella vulgaris (CVS) was examined for its protective effect on 5-fluorouracil(5FU)-induced myelosuppression and indigenous infection in mice. Subcutaneous administration of CVS greatly reduced the mortality of non-tumor-bearing mice given a high dose of 5FU, and could increase the LD50 value of 5FU for these mice. After 5FU treatment, indigenous infection developed probably as a result of the impairment of the host defense system. CVS reduced the incidence of indigenous infections and this effect was attributable to the acceleration of recovery from 5FU-induced myelosuppression. Early recovery of hematopoietic stem cells, or cells responding to interleukin-3 or granulocyte/macrophage-colony-stimulating factor, was especially observed in the bone marrow of CVS-treated mice on days 4 – 9 after the injection of 5FU. When tumor-bearing mice were given CVS during treatment with 5FU, CVS prolonged the survival of mice without affecting the antitumor activity of 5FU. In addition, CVS was itself shown to exert an antitumor effect. These results suggested that CVS may be beneficial for the alleviation of side-effects in cancer chemotherapy without affecting the antitumor activity of the chemotherapeutic agent.

The bacterial elimination after infection with Listeria monocytogenes was impaired in mice with murine acquired immunodeficiency syndrome (MAIDS) by infection with LP-BM5 murine leukemia virus. Oral administration of hot water extracts of Chlorella vulgaris (CVE) restored the capacity of MAIDS mice to eliminate L. monocytogenes in association with improvement of the deteriorated immune response to L. monocytogenes. DTH response to Listeria in CVE-treated MAIDS mice was significantly higher than that of MAIDS mice after Listeria infection in association with increases in number of CD4+CD8− and CD4−CD8+ αβ T-cells in the infected sites. CVE might be effective in the treatment of opportunistic infection in retrovirus-induced immunodeficient patients.

The effects of oral administration of a hot water extract of Chlorella vulgaris (CVE) on the restoration of the leukocyte number and on the resistance against Escherichia coli infection were examined in cyclophosphamide (CY)-treated rats. Male Fischer rats (F344/DuCrj) were administered orally 1000 mg/kg of CVE for 14 days and injected intraperitoneally with a single dose of CY (50 mg/kg) (day 0) one day after the 14th CVE administration. CVE was further administered continuously after CY treatment until the rats were sacrificed for analysis. The number of bone marrow cells in the CY + CVE group was significantly higher on day 7 after CY treatment than that in the CY-treated group. The number of spleen cells in the CY + CVE group became significantly higher on day 11 than that in the CY-treated group. In the peripheral blood, the number of PMN recovered efficiently in the CY + CVE group in comparison with the CY-treated group on day 7. When E. coli was injected i.p. into normal, CY-treated, and CY + CVE-treated rats on day 6, the difference in number of bacteria among these three groups was most prominent before 6 h, that is, the number in the CY + CVE group was remarkably lower than those in the CY-treated group, and even in the control group, among all organs so far tested.

The effects of Chlorella vulgaris extract (CVE-A) on the recovery of leukocyte number and the augmentation of resistance to bacterial infection were examined in CDF1 mice made neutropenic by cyclophosphamide (CY). They were treated intraperitoneally with CY (150 mg/kg) on day 0, and were given CVE-A (50 mg/kg) subcutaneously (s.c.) every other day from day 1 to day 13 after CY treatment. CVE-A accelerated the recovery of polymorphonuclear leukocytes (PMN) in the peripheral blood in CY-treated mice. The number of granulocyte/monocyte-progenitor cells (CFU-GM) in the spleen increased rapidly and highly after the administration of CVE-A in CY-treated mice, in contrast to the absence of change due to CVE-A in the number of bone marrow cells in CY-treated mice. Administration of CVE-A in CY-treated mice enhanced the accumulation of PMN in the inflammatory site and the activity of the accumulated leukocyte cells in luminol-dependent chemiluminescence. The mice became highly susceptible to an intraperitoneal infection with E. coli on day 4 after CY treatment, whereas the mice given CVE-A showed an enhanced resistance against E. coli infection, irrespective of the timing of challenge. The bacterial number in CY-treated mice increased explosively after inoculation, resulting in death within 24 h. A progressive elimination of bacteria was observed from 6 h in the peritoneal cavity, spleen and liver of CY-treated mice given CVE-A s.c. These results indicate that CVE-A can be used as a potent stimulant of nonspecific resistance to infection in neutropenic mice.

An active substance with antitumor activity (ARS2) was purified from the culture media of Chlorella vulgaris and found to be a glycoprotein with a molecular weight of 63,100 amu, as determined by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. ARS2 contains 66.9 % carbohydrate, mainly D-galactose, and 35.2% protein. The carbohydrate moiety has a β-1,6-D-galactopyranose backbone, as determined by methylation analysis and 13 C-NMR. Apparently, the protein moiety, whose 15 amino acid sequence at the NH 2 -terminus, we determined as DVGEAFPTVVDALVA, is necessary for the antitumor activity, as assessed by hydrazinolysis, periodate oxidation, and proteolysis.

Chlorella vulgaris, an unicellular green algae, or its acetone-extract (Ac-Ex) were administered orally to Meth A tumor bearing BALB/c or (BALB/c x DBA/2)F1 (CDF1) mice. When CDF1 mice were fed daily with 10% dried powder of Chlorella vulgaris (CVP) containing diet before and after Meth A tumor inoculation, the growth of rechallenged Meth A tumor was significantly suppressed in an antigen-specific manner. Augmentation of antitumor resistance was exhibited also by Winn assay using lymph node cells of tumor-bearing mice orally administered with CVP or Ac-Ex. Antigen-specific concomitant immunity in these mice were mediated by cytostatic T cells but not by cytotoxic T cells. Natural killer cells seemed not to contribute in antitumor resistance in this system.

In previous studies, we demonstrated that a hot water extract of Chlorella vulgaris (CVE) augmented the resistance against an intraperitoneal infection with Escherichia coli by its intraperitoneal, intravenous or subcutaneous administration. The augmented resistance appeared to be attributable to the enhanced activity of polymorphonuclear leukocytes (PMN). In this study, the effect of oral administration of CVE against Escherichia coli infection was examined. Male Fisher rats (F344/DuCrj) were administered 1000 mg/kg of CVE orally for 14 days and challenged with 2.7 x 10(8) Escherichia coli intraperitoneally. The numbers of living bacteria in the peritoneal cavity, blood, spleen and liver at 1, 6, and 24 h after the inoculation were counted. The bacterial numbers increased during 1-6 h and reached the peak at 6 h in both control and CVE-administered groups. The bacterial numbers decreased to an undetectable level at 24 h in both groups. In a CVE-administered group, the numbers of viable bacteria in each organ were remarkably lower than those in a control group in all organs so far tested. Whereas, the leukocyte numbers, especially PMN numbers, in the peritoneal cavity and peripheral blood maintained higher levels in the CVE-administered group at 6 h after E. coli inoculation. Chemiluminescent responses of peritoneal exudate cells induced by casein or E. coli were higher in a CVE-administered group. These results form the basis for the judgment that the degree of effectiveness of bacteria clearance from the peritoneal cavity shown by oral CVE administration may be strong enough to warrant developing this material as a new type of biological response modifier.

dd系の雄マウスを2%のChoを添加した高Cho食で7日間飼育した場合, 肝のCho値, 中性脂肪値ならびに総脂質値が著しく上昇した。一方, 10%のクロレラ粉末添加飼料で飼育したマウスに高Cho食を与えた場合には, その肝中のCho値, 中性脂肪値ならびに総脂質値の上昇は認められず, それぞれ対照群に近い値を示した。また血清Cho値も同様に, クロレラ粉末添加によって抑制される傾向がうかがわれた。以上のことから, クロレラがマウスの肝での脂質または血清中のCho値を低下させることがわかった。ヒトの場合においても, 脂質制限を行なわずに, 普通食を自由にとらせながら, クロレラを1日20錠 (5g), 3カ月間投与した結果, 血清Cho値の低下を認めた。とくに, 入院患者で, 5カ月間の平均値が200～250mg/dlの範囲にある比較的軽度の高血清Cho値を示す患者では著明で, クロレラ投与の結果, 血清Cho値は, ほぼ正常域にまで低下した。250mg/dl以上という高度の血清Cho値を示す患者では, 低下の傾向は認められたものの, 3カ月投与の期間内では, 正常域までの低下は起こらなかった。

老年期に入る時期については定かではなく, 個人それぞれにより異なるが歯科医学の立場からは特に顎口腔の形態的, 機能的両面より捕らえていかねばならない.そこで顎口腔機能異常を高齢者を対象としてその実態を報告した.以上を要約するとつぎのようになる.1. 顎口腔機能異常者416名を対象とした結果50歳以上の患者は22%を占め, 内, 全体の4.3%にあたる18名は65歳以上の高齢者であった.2. 50歳以上の患者の主訴は, 三大症状が多く顎口腔機能異常者全体の傾向と同様であった.3. 誘発したと考えられる因子として補綴物, 歯冠崩壊, 歯の欠損などがあげられる.4. 来院に至る期間として全体では3ヵ月, 50歳以上では6ヵ月を境として多くなり全体と同じく2年以上が最も多かった.5. 50歳以上の患者の現症として, 疼痛は全体像と同様であるが, 関節音はタイミング, 種類に特徴がみられた.6. 50歳以上の患者の内, 64名についての顎関節X線写真より形態変化, 変位のみられなかった症例はそれぞれ27例 (42%), 18例 (28%) であったが増齢と共に両側にわたり異常となる傾向がみられた.7. 口腔内所見として50歳以上では修復が広範囲にわたる患者が多く, 遊離端欠損様式が増え65歳以上では総義歯患者が増えた.咬合高径は両側共に低下していることが多かった.タッピング・クレンチングポイントは高齢者では不明分が多くなるが, 女性では不安定であることが多かった.