Biomedical subjects

T Ebina

Publications and source records attributed to T Ebina.

At least 73 records · Page 4Linked to original sources

PubMed1990

Depressor effects and pharmacokinetics of single and consecutive doses of delapril in hypertensive patients with normal or impaired renal function.

The antihypertensive effects and pharmacokinetic properties of delapril, an angiotensin-converting enzyme (ACE) inhibitor, were investigated in hypertensive patients with normal renal function (NRF; n = 6) and in those with impaired renal function (IRF; n = 5). A 15-mg oral dose of delapril was given once on the first and last days, and twice daily on the other days. The measurement of blood pressure and sampling were done at 0, 1, 2, 4, 6, 12, and 24 hours postdose on the first and last days of treatment. Plasma and urinary concentrations of delapril and its metabolites were measured by HPLC. ACE activity was suppressed from 1 hour after the first dose to 24 hours after the last dose of delapril in both the NRF and IRF groups. During the consecutive dosing, significant BP falls were observed from 1 hour postdose of delapril to 24 hours in the NRF group and to 6 hours in the IRF group. Peak plasma concentrations of 5-hydroxydelapril diacid and areas under the plasma concentration-time curve (AUC) of both delapril diacid and 5-hydroxydelapril diacid in the IRF group were significantly higher (p less than 0.001 or 0.05) than in the NRF group. No significant increase of pharmacokinetic parameters in repeated dosing was observed in both the NRF and IRF groups. Significant positive correlations (p less than 0.001) were found between the inverse of creatinine clearance and the AUCs of the active diacid metabolites in single and consecutive doses.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1990

Glucose and lipid metabolism during long-term treatment with cilazapril in hypertensive patients with or without impaired glucose metabolism.

The effects of long-term cilazapril therapy on glucose tolerance and serum lipid profiles were investigated in 19 hypertensive patients: seven with normal glucose tolerance and 12 with glucose intolerance (including three patients with noninsulin-dependent diabetes). Cilazapril was administered once daily for a mean duration of 6.4 months. A 75-g oral glucose tolerance test was performed before and during long-term therapy with cilazapril. Cilazapril produced satisfactory control of blood pressure in both patient groups during long-term therapy. It was well tolerated by all patients. Neither fasting nor postglucose-load venous plasma glucose levels were altered in either group of patients, and no patients with normal glucose tolerance developed diabetes mellitus during the study. There were no significant changes in the insulinogenic index (delta IRI/delta BS at 30 min postglucoseload) in patients with normal or impaired glucose tolerance. No significant changes in fasting levels of serum cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides were observed in either group. These results suggest that effective long-term cilazapril therapy does not compromise glucose or lipid metabolism in hypertensive patients. Cilazapril may have a clinical advantage in that it can be given to hypertensive patients without concern that it might alter their serum lipid concentrations or impair glucose tolerance.

Adult↗

PubMed1990

Pharmacokinetics and antihypertensive effects of lisinopril in hypertensive patients with normal and impaired renal function.

The antihypertensive effects and pharmacokinetic properties of lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, were investigated in hypertensive patients with normal renal function (NRF, mean serum creatinine 1.0 mg/dl, n = 9) and those with impaired renal function (IRF, mean serum creatinine 1.7 mg/dl, n = 8). Lisinopril was administered orally (10-mg dose once daily for 5 or 8 days). Measurement of blood pressure (BP) and sampling of blood specimens were made on the first and last days of treatment. During consecutive dosing of lisinopril, its antihypertensive effects were sustained for greater than or equal to 12 h with less diurnal variation of BP. Serum ACE activity was markedly suppressed for 24 h. Plasma levels of lisinopril in the IRF group were higher than those in NRF with significant differences in the peak levels and areas under the plasma concentration time curve (AUC). A significant inverse correlation was found between the creatinine clearance and the AUC for lisinopril. These results suggest that lisinopril has a long-lasting action and that it is a useful antihypertensive agent for controlling BP in patients with either NRF or mild IRF. When administered for an extended period, however, more careful consideration should be given to the dose in patients with IRF than in patients with NRF to minimize the possibility of untoward side effects.

Adult↗

PubMed1990

Gastroenteritis in suckling mice caused by human rotavirus can be prevented with egg yolk immunoglobulin (IgY) and treated with a protein-bound polysaccharide preparation (PSK).

Oral inoculation of human rotavirus MO strain (serotype 3) into 5-day-old BALB/c mice cause gastroenteritis characterized by diarrhea. Clinical symptoms, histopathological changes in the small intestine, and the detection of rotavirus antigen in enterocytes were all characteristic of rotavirus-induced gastroenteritis. Using this small animal model, passive protection of suckling mice against human rotavirus infection was achieved with the use of immunoglobulin (IgY) from the yolks of eggs of rotavirus-immunized hens. When IgY against a rotavirus strain homotypic to the challenge virus (MO strain) was administered in the mice, complete protection against rotavirus infection was achieved. On the other hand, with oral administration of IgY against a heterotypic strain (serotype 1, Wa strain), a lower protective effect was nevertheless obtained. The four different strains of human rotavirus (Wa, KUN, MO, and ST3) were inactivated in vitro by treatment with PSK, a protein-bound polysaccharide preparation, in a dose-dependent manner. Oral administration of 2.5 mg of PSK caused a therapeutic effect on experimentally MO-infected suckling mice. The antiviral effect of PSK was indicated by the reduction of the duration of diarrhea.

Animals↗

PubMed1990

Antitumor effect of PSK at a distant site: inductions of interleukin-8-like factor and macrophage chemotactic factor in murine tumor.

The antitumor effect of PSK, a Coriolus preparation, at a distant site was analyzed with the use of a double grafted tumor system in which male BALB/c mice received simultaneous intradermal inoculations of Meth-A tumor in the right (10(6) cells) and the left (2 x 10(5) cells) flanks and were then injected with PSK in the right tumor on the third day thereafter. The antitumor effect of intratumoral administration of PSK in the right tumor on days 3, 4 and 5 was compared with the effect of surgical resection of the right tumor on day 5. Three out of 8 mice given PSK intratumorally became tumor-free whereas no mouse tumor-free in the left flank was found among the surgically resected mice. As regards sinecomitant immunity, tumor inoculation into the right flank followed by intra-tumoral administration of PSK on days 3 and 5 and surgical excision of the primary tumor on day 6 resulted in complete rejection of a tumor challenge in the left flank on day 21. The combination of presurgical intratumoral injections of PSK (more than 2 times) and postoperative oral administration of PSK appeared to be most effective in eradicating secondary tumors. Isolated TILs (tumor-infiltrating lymphocytes), obtained from the right tumor (treated with PSK) and the left tumor on day 10 in the double grafted tumor system were cultured in RPMI1640 with 10% fetal calf serum for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophils or macrophages. Significant neutrophil chemotactic factor (NCF) and macrophage chemotactic factor (MCF) activities were detected in the culture media from PSK-treated TILs that had been cultured for 24 h. Neither significant neutrophil nor macrophage chemotactic activity was detected in the media from untreated TILs. NCF and MCF activities were also detected in the culture supernatant from PSK-treated tumor tissue on day 6. PSK-induced NCF in the murine tumor was neutralized by treatment with anti-human IL-8 IgG, and might be murine IL-8-like factor. Therefore, neutrophil and macrophage infiltrations of tumors following intratumoral injections of PSK are probably mediated by inductions of IL-8-like factor and MCF.

Animals↗

PubMed1990

[Adrenal tumors associated with renal cell carcinoma].

We experienced two cases with renal cell carcinoma who showed enlargement of the contralateral adrenal gland. In case 1, the enlarged adrenal gland was a non-functioning adrenal adenoma, and in case 2, it was a metastatic adrenal tumor. Non-functioning adrenal adenomas are benign tumors of the adrenal cortex often found incidentally at autopsy or on computed tomography (CT) studies of the upper abdomen. Adrenal adenomas have been reported to occur in 9.5-14% of patients with renal cell carcinoma, while the incidence being 1.5-8.7% in the general population. Since metastases of renal cell carcinoma to the adrenal glands are not uncommon, it is important to distinguish between non-functioning adrenal adenomas and metastatic tumors. Therefore, we studied the incidence of adrenal tumors (including metastatic tumors and benign tumors) in patients with renal cell carcinoma who underwent the abdominal CT study in our hospital. From 1982 to 1989, CT had been performed in 67 patients with renal cell carcinoma. Six adrenal masses were identified with CT in these patients. Three out of the 6 patients probably had metastatic tumors and one of the 3 adrenal masses was pathologically diagnosed as metastatic tumor. The other three masses were benign on pathology and only one of them was pathologically diagnosed as non-functioning adrenal adenoma. The incidence of adrenal adenomas on the CT study was lower than that of previous studies based on autopsy. The reasons of this difference in results between their studies and ours are not clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1990

[Antitumor effect of Cepharanthin in the double grafted tumor system].

The antitumor effect of Cepharanthin (CR) in a new experimental mouse model was studied. Intratumoral administration of CR strongly inhibited the growth of Meth-A solid tumors in male BALB/c mice and led to a complete regression of tumors and resistance to reinoculated tumor. Subsequently, the antimetastatic effect of CR was examined in the double grafted tumor system, in which mice first received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 x 10(5) cells) flanks and were then injected with 0.5 mg of CR in the right tumor on days 3, 4 and 5. CR inhibited the growth of not only the right but also the left, nontreated tumor. Immunized spleen cells were taken from mice which had been cured with the intratumoral administration of CR. Adoptive transfer of CR immunized spleen cells caused the complete regression of Meth-A tumors. The effector cell activity was lost only after treatment with anti-Lyt-1 antibody. These results suggest that intratumoral administration of CR might induce Lyt-1 positive cytotoxic cells in the spleen and the left, non-treated tumor. In BALB/c nude mice, CR inhibited the growth of the right tumor but did not the left tumor. Therefore, the antitumor activity of CR on the left tumor in the double grafted tumor system is associated with a sequential immune mechanism in which T cells may play an important role. The antitumor effect of CR on the right tumor is direct cytotoxic effect. TILs (tumor infiltrating lymphocytes) obtained from left and right sides tumors treated with CR were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TILs from both sides clearly inhibited the growth of admixed Meth-A cells and seems to play an important role on antitumor effect in both tumors.

Alkaloids↗

PubMed1990

[Antitumor effect of a novel antitumor compound, NC-190, in the double grafted tumor system].

The antitumor effect of NC-190, N-beta-dimethylaminoethyl-9-carboxy-5-hydroxy-10-methoxybenzo [alpha] phenazine-6-carboxamide sodium salt, with a new experimental mouse model was studied. Intratumoral administration of NC-190 strongly inhibited the growth of Meth-A solid tumors in male BALB/c mice and led to a complete tumor regression and also resistance to the reinoculated tumor. Subsequently, the anti-metastatic effect of NC-190 was examined in the double grafted tumor system, in which mice first received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with 25 micrograms of NC-190 in the right tumor on days 3, 4 and 5. NC-190 inhibited the growth of not only the right but also the left, non-treated tumor. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of NC-190. Adoptive transfer of NC-190 immunized spleen cells caused a complete regression of Meth-A tumors. The effector cell activity was lost only after treatment with anti-Lyt-2 antibody. These results suggest that intratumoral administration of NC-190 might induce Lyt-2 positive cytotoxic cells in the spleen and the left, non-treated tumor. In BALB/c nude mice, NC-190 inhibited slightly the growth of the right tumor but did not that of the left tumor. Therefore, the antitumor activity of NC-190 in the double grafted tumor system was judged as associated with a sequential immune mechanism in which T cells may play an important role. TILs (tumor infiltrating lymphocytes) obtained from the left and right sides tumors treated with NC-190 were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TILs obtained from neither sides inhibited the growth of admixed Meth-A cells. Different from immunopotentiators such PSK or IL-1, NC-190 enhanced neither concomitant immunity nor sinecomitant immunity.

Animals↗

PubMed1989

The "double grafted tumor system", proposed to find effector cells in the analyses of antitumor effect of BRMs.

The antitumor effects of three biological response modifiers (BRMs; PSK, IFN alpha A/D and OK432) and two chemotherapeutics (Mitomycin C and Neocarzinostatin) in a new experimental mouse model, the "double grafted tumor system," were evaluated. BALB/c mice received simultaneous inoculations of Meth A fibrosarcoma cells on right flank (1 x 10(6) cells) and left flank (2 x 10(5) cells) on day 0, and drugs were given intratumorally into the right-flank tumor on day 3. The growth of the left-flank tumor was the real target for the evaluation of a given drug after 21 days. All tested five agents successfully cured the drug-injected right tumor with a pre-determined optimum dose. In addition, PSK, OK432, IFN alpha A/D and MMC among the five, inhibited the left-flank tumor, whereas no inhibition was observed when treated with NCS. To understand the mechanism by which the antitumor effect of the above four agents is able to influence the growth of tumor on the other side, tumor cells (2 x 10(5) cells) inoculated only into the left flank were treated with drugs given subcutaneously to the right flank (single tumor system). Among the four, MMC exhibited an effect similar to that obtained in the double tumor system, and IFN alpha A/D showed a less pronounced but still definite antitumor effect. However, PSK and OK432 failed to express anti-tumor effect in the single tumor system. These results obtained with PSK, OK432 and IFN alpha A/D suggest that the effect of the drug on the left-tumor may be mediated by certain effector cells, which are specifically induced by injection of the drug, in the right-tumor tissues. When effector cell analysis was conducted with spleen cells obtained after PSK treatment by means of intratumoral adoptive transfer into 3-day Meth A bearing recipients, these cells were shown to be Lyt-1+2(-)-T and L3T4(+)-T cell.

Animals↗

PubMed1989

Antitumor effect of interleukin-1 beta in the double grafted tumor system.

The antimetastatic effect of recombinant human interleukin-1 beta (rIL-1 beta) in a new experimental mouse model was studied. Intratumoral administration of IL-1 beta strongly inhibited the growth of Meth-A solid tumors in male BALB/c mice and led to a complete regression of tumors and resistance to reinoculated tumor. Subsequently, the anti-metastatic effect of IL-1 beta was examined in the double grafted tumor system, in which mice first received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with 0.2 micrograms of IL-1 beta in the right tumor on days 3, 4 and 5. IL-1 beta significantly inhibited the growth of the left, non-treated tumor. When mice received only an inoculation of Meth-A (2 X 10(5) cells) in the left flank and were injected subcutaneously with IL-1 beta into the right flank on day 3 (single tumor system), there was no inhibition of the growth of the left, non-treated tumor. These findings suggest that intratumoral IL-1 beta immunotherapy in one region has an effect on tumor growth in another region. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of IL-1 beta. Adoptive transfer of the immunized spleen cells caused the complete regression of Meth-A tumors. These results suggest that intratumoral administration of IL-1 beta might induce cytotoxic cells in the left non-treated tumor of the double grafted tumor system and bring about the regression of metastatic tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Antitumor effect of PSK: role of regional lymph nodes and enhancement of concomitant and sinecomitant immunity in the mouse.

PSK, a Coriolus preparation, inhibited the growth of not only the right but also the left, non-treated tumor in a double grafted tumor system. In order to examine the role of lymph nodes and the spleen in the antitumor activity of PSK, regional (axillary and inguinal) lymph nodes and spleen were resected. Since in resected mice the antitumor activity of PSK against the right and left tumors was weakened, the regional lymph nodes and the spleen probably have a very important role in the antimetastatic effect of intratumoral administration of PSK. TIL (tumor-infiltrating lymphocytes) obtained from left and right side tumors treated with PSK were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TIL from both sides clearly inhibited the growth of admixed Meth-A cells, but control TIL did not. A primary growth of Meth-A sarcoma inoculated into the right flank resulted in the generation of concomitant immunity to the growth of a second graft of the same tumor cells in the left flank. A significant inhibitory effect on the proliferation of the tumor cells inoculated secondarily was shown in mice bearing a primary right tumor that had previously been inoculated with PSK 3 times. After surgical excision of the primary tumor on day 6, daily oral administration of PSK significantly inhibited the growth of the secondary tumor inoculated on day 21, that is, PSK treatment also enhanced sinecomitant immunity. These observations suggest that presurgical intratumoral injection and postoperative oral administration of PSK are highly effective in eradicating metastatic tumors.

Adjuvants, Immunologic↗

PubMed1989

Antiviral activity of carboxyethylgermanium sesquioxide (Ge-132) in mice infected with influenza virus.

The protective effect of carboxyethylgermanium sesquioxide (Ge-132) in mice infected with a mouse-adapted strain of influenza virus (H2N2) was investigated. When mice were exposed to a 10 LD50 dose of influenza virus via aerosol and were treated orally with 20 or 100 mg/kg of Ge-132 daily for 6 consecutive days, a significant protective effect was demonstrated. The antiviral effect of Ge-132 was indicated by an increase of survivors, a prolongation of mean survival days, an inhibition of the development of lung consolidation, and a decrease of virus titer in lung tissues, as compared to infected control mice treated with phosphate-buffered saline. Natural killer (NK) cell activity in the spleens and lungs of the infected mice was also significantly augmented after the oral administration of Ge-132. In addition, NK cells stimulated with Ge-132 in vivo showed killing activity against NK-insensitive Meth-A cells infected with influenza virus. Because no virucidal or virustatic activities of Ge-132 on the virus were found in vitro, this protective effect in mice against influenza virus infection may be displayed through immunomodulating activities of this compound such as the augmentation of NK cell activity.

Animals↗

PubMed1989

[An autopsy case of rectal cancer receiving cisplatin at total dose of 3.250 mg and platinum concentrations in autopsy tissue samples].

An autopsy case of a 57-year-old man who had received cisplatin, total dose of 3,250 mg (1,920 mg/m2) after proctectomy for advanced rectal cancer with hepatic metastasis is reported. Platinum concentrations in autopsy tissue samples are also reported. Cisplatin at a dose of 20-40 mg was administered intravenously once a week for 82 weeks, but renal failure did not occur. The patient died 529 days after his last cisplatin therapy, due to acute suppurative cholangitis. On autopsy, the hepatic hilar metastasis involved the bile duct, but the other metastasis of the liver became regeneration and necrosis, and the kidneys showed few findings but congestion and arteriosclerotic change. The spleen evidenced mild hemosiderosis. Tissue samples obtained at the time of autopsy were assayed for platinum using flameless atomic absorption spectrometry. The spleen had the highest concentration, about 2.7 times as high as that of the liver. The liver, the heart and the kidneys had high platinum concentrations (greater than 3.04 micrograms/g), but those of the jejunum and the ileum were low (less than 0.95 micrograms/g). Although cisplatin, FT 207 and krestin were effective for the rectal cancer, platinum was undetectable (less than 0.13 micrograms/g) in the ascending and the transverse colons.

Adenocarcinoma↗

PubMed1988

Antitumor effector mechanism at a distant site in the double grafted tumor system of PSK, a protein-bound polysaccharide preparation.

The antitumor effect at a distant site of PSK, a Coriolus preparation, was analyzed with the double grafted tumor system in which BALB/c mice received simultaneous intradermal inoculations of Meth-A tumor in the right (10(6) cells) and left (2 x 10(5) cells) flanks and were then injected with PSK in the right-flank tumor on day 3. PSK inhibited the growth of not only the right but also the left (non-treated) tumor. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of 5 mg of PSK and were injected into the Meth-A tumor on day 3. Adoptive transfer of PSK immunized spleen cells caused the complete regression of Meth-A tumors. The effector cell activity was lost only after treatment with anti-Lyt-1 monoclonal antibody plus complement. Spleen cells and right and left regional lymph node cells prepared from PSK immunized mice were examined for Thy-1, Lyt-1, Lyt-2 and asialo GM1 phenotypes. The number of Lyt-1-positive lymphocytes increased in the right regional lymph nodes after intratumoral administration of PSK. A massive accumulation of macrophages and polymorphonuclear leukocytes was found in the right tumor and an infiltration of macrophages and Lyt-2-positive lymphocytes was found in the left (non-treated) tumor by immunohistochemical analyses. These results suggest that intratumoral administration of PSK induces Lyt-1-positive cells first in regional lymph nodes, then in the spleen, and subsequently induces macrophages and Lyt-2-positive cells in the left (non-treated) tumor, thus bringing about the regression of metastatic tumors.

Animals↗

PubMed1987

Serologic characteristics of a human rotavirus isolate, AU-1, which has a "long" RNA pattern and subgroup I specificity.

An unusual human rotavirus (HRV) isolate, designated AU-1, has a "long" RNA electrophoretic pattern and subgroup I specificity, in contrast to properties common to HRVs previously isolated. Hemagglutination activity of the AU-1 strain was demonstrated using erythrocytes of 1-day-old chicken. Neutralization assays revealed that the AU-1 strain was crossneutralized by hyperimmune antisera against the MO strain (serotype 3). However, antiserum directed against a reassortant in which the gene for Vp7 was replaced by the corresponding AU-1 gene neutralized the AU-1 strain to a significantly higher titer than the MO strain.

Hemagglutination Tests↗

PubMed1987

Clinical effects of MND-19 (Inosiplex) on subacute sclerosing panencephalitis--a multi-institutional collaborative study--The Inosiplex-SSPE Research Committee.

A total of 151 cases of subacute sclerosing panencephalitis (SSPE), comprising 89 cases treated with MND-19 (Inosiplex) and 62 untreated cases, were retrospectively investigated as to background characteristics, survival rate and clinical course in order to compare the findings in the 2 groups of cases. The survival rate for the cases treated with MND-19 (MND-19-treated group) was significantly higher than that for the untreated cases (control group), which was also true on stratified analysis or on smoothing of the background factors by means of Cox's multiple regression model. Investigation of the clinical course revealed that progression through the disease stages was significantly slow in the MND-19-treated group, compared with in the control group. Global rating of the clinical course showed that a prolonged remission was obtained in more MND-19-treated cases than control cases. The measles virus antibody titer was in no way affected in the former group. Side effects of MND-19 were observed in 17 of the 89 treated cases (19.1%).

Adolescent↗

PubMed1987

[Antitumor effect of PSK (1). Interferon-inducing activity and intratumoral administration].

After oral administration of 20 mg/kg of PSK, a significant level of interferon (IFN) activity was detected in the sera of BCG (1 mg/mouse)-sensitized mice. A low titer of IFN was also detected in the sera of all of 4 cancer patients after 3 g/day oral administration of PSK for 7 consecutive days. Intratumoral administration of PSK (5 mg/mouse) strongly inhibited the growth of Meth-A solid tumors in male BALB/c mice and led to complete regression of tumors and resistance to reinoculated tumors in the host animals. Subsequently, the antimetastatic effect of PSK was examined in a "double grafted tumor system" in which mice first received simultaneous intradermal inoculations of Meth-A in the right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with PSK in the right tumor on day 3. PSK significantly inhibited the growth of the left, non-treated tumor. When mice received an inoculation of Meth-A (2 X 10(5) cells) in the left flank and PSK was injected subcutaneously in the right flank on day 3 (single tumor system), the growth of the tumor was not inhibited. These findings suggest that intratumoral PSK immunotherapy in one region has an effect on tumor growth in another region.

Aged↗

PubMed1987

[Antitumor effect of PSK (2): effector mechanism of the antimetastatic effect in the "double grafted tumor system"].

The antimetastatic effect of PSK was analysed with the "double grafted tumor system" in which BALB/c mice received simultaneous intradermal inoculations of Meth-A in the right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with PSK in the right tumor on day 3. PSK inhibited the growth of not only the right but also the left, non-treated tumor. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of 5 mg of PSK. On day 3, one hour after intravenous injection of cyclophosphamide, immunized spleen cells (2 X 10(7) cells/mouse) were injected into the Meth-A tumor. Adoptive transfer of PSK immunized spleen cells caused the complete regression of Meth-A tumors. The effector cell activity was lost only after treatment with anti-Lyt-1 monoclonal antibody plus complement. Spleen cells and right and left regional (axillary and inguinal) lymph node cells prepared from PSK immunized mice 7 and 14 days after tumor inoculation were examined for Thy-1, Lyt-1, Lyt-2 and asialo GM1 phenotypes by flow cytometric analysis. The number of Lyt-1 positive lymphocytes increased in the right regional lymph nodes after intratumoral administration of PSK. Immunohistochemical analyses of the right and left tumors in the "double grafted tumor system" on day 7 and day 14 were carried out by PAP (peroxidase antiperoxidase) method. Necrosis, karyoklasis and a massive accumulation of macrophages were found in the right tumor after intratumoral administration of PSK. An infiltration of macrophages and Lyt-2 positive lymphocytes was found in the left, non-treated tumor. These results suggest that intratumoral administration of PSK might induce Lyt-1 positive cells first in regional lymph nodes, then in the spleen, and subsequently induce macrophages and Lyt-2 positive cells in the left, non-treated tumor of the "double grafted tumor system", thus bringing about the regression of metastatic tumors.

Animals↗