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T Ebina

Publications and source records attributed to T Ebina.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of initial distribution volume of glucose and plasma volume in thoracic fluid-accumulated patients.

OBJECTIVE: We have reported that initial distribution volume of glucose indicates the central extracellular fluid volume in the presence of fluid gain or loss. The purpose of this study was to describe changes in initial distribution volume of glucose, plasma volume determined by the indocyanine green dilution method (PV-ICG), and thoracic fluid content by thoracic electrical bioimpedance in patients with or without apparent thoracic fluid accumulation in the absence of pleural effusion. We also sought to test whether initial distribution volume of glucose rather than PV-ICG mirrors thoracic fluid content. DESIGN: Prospective, clinical study. SETTING: General intensive care unit. PATIENTS: Eleven consecutive patients with apparent thoracic fluid accumulation as judged by thoracic fluid content >0.05/ohm and underlying pathology and 20 consecutive acute myocardial infarction patients within 24 hrs after its onset were selected for study. None of the acute myocardial infarction patients had thoracic fluid content >0.05/ohm. INTERVENTIONS: Five grams of glucose and 25 mg of indocyanine green were administered simultaneously to calculate initial distribution volume of glucose and PV-ICG daily for the fluid-accumulated patients, and the same dosages were administered to the acute myocardial infarction patients immediately after their admission to the intensive care unit after percutaneous coronary angioplasty. Only the data on the day of the maximal and minimal thoracic fluid content in the fluid-accumulated patients were used for the study. The relationship between these two fluid volumes and thoracic fluid content was evaluated in the two patient groups. MEASUREMENTS AND MAIN RESULTS: Initial distribution volume of glucose and thoracic fluid content rather than PV-ICG and thoracic fluid content moved together in the same direction in each fluid-accumulated patient. Neither pulmonary artery occlusion pressure, central venous pressure, nor PV-ICG produced a better correlation with cardiac index when compared with initial distribution volume of glucose in patients with or without thoracic fluid accumulation. CONCLUSIONS: We suggest that initial distribution volume of glucose rather than PV-ICG is a better indicator of the intrathoracic blood volume status, even although intravenously administered glucose cannot stay in the intravascular compartment.

APACHE↗
PubMed2001

Effector mechanism and clinical response of BAK (BRM-activated killer) immuno-cell therapy for maintaining satisfactory QOL of advanced cancer patients utilizing CD56-positive NIE (neuro-immune-endocrine) cells.

A new type of immuno-cell therapy called BRM-activated killer (BAK) therapy using non-MHC-restricted lymphocytes, CD56-positive cells, was devised. Peripheral blood lymphocytes were selected by immobilization with anti-CD3 monoclonal antibody and cultured for 2 weeks in the presence of IL-2. Thereafter, they were reactivated by 1,000 U/ml of IFN-alpha for 15 min. Twenty-six outpatients with cancer whose performance status were over 80% on Karnofsky scale were selected for this study. About 6 x 10(9) BAK cells were returned by intravenous drip infusion, at one month intervals at an outpatient clinic to each of 20 advanced cancer patients in whom many metastatic lesions were found postoperatively, and to 6 patients with no postoperatively detectable metastases. The proportion of CD56-positive cells increased from 20% to 50% with culture. CD56-positive cells have strong cytotoxic activity and produced 20 ng/10(9) cells of beta-endorphin, an intracerebral hormone. During the course of BAK therapy, we adopted the Face scale as a QOL indicator. The QOL of all patients remained satisfactory or improved. Beta-endorphin is thought to make patients feel well and maintains good QOL because of its potent analgesic, sedative activity. From that facts that CD56 is a neural cell adhesion molecule and a member of the Ig superfamily, and that the CD56-positive cell produces beta-endorphin, we concluded that the CD56-positive cell is a multifunctional, integrated NIE (neuro-immune-endocrine) cell. Administration of BAK cells allowed all 20 advanced cancer patients with metastases to survive for over one year. All 6 patients receiving the same therapy for prevention of postoperative metastasis have been recurrence-free for one to five years.

Aged↗
PubMed2001

[Continuous intrathecal administration of nicardipine using a portable infusion pump system for management of vasospasm after subarachnoid hemorrhage].

We studied the feasibility of intrathecal nicardipine administration using a portable infusion pump system in five cases (two males and three females) of subarachnoid hemorrhage (SAH). All of the five cases manifested severe SAH of Hunt & Kosnic grade 3 or 4, and Fisher CT group 3. Aneurysmal sites of five cases were as follows: three internal carotid-posterior communicating artery (IC-PC) aneurysms and two anterior communicating artery (Acom) aneurysms. The container of the infusion pump system was filled with 105 ml of nicardipine-saline solution (2:1), and this system was connected to the cisternal tube. The solution was continuously injected at a daily dose of 12 ml (8 mg of nicardipine). This therapy was continued for 14 days, and new nicardipine solution was supplied only once at 8 days after the operation during this therapy. No postural restraint of patients was necessary, even during physical movement for rehabilitation. Postoperative angiography was performed in three of five cases at one week after the operation. No angiographic vasospasm was observed in any of the three cases. Symptomatic vasospasm was observed in one case of right IC-PC aneurysm as a transient total aphasia and right hemiplegia, which recovered within several hours due to induced hypervolemia and hypertension therapy. Mild meningitis at 14 days after the operation complicated this treatment in one case, but it improved in a few days after the cisternal tube was removed. It was speculated that meningitis was caused by cerebrospinal fluid leakage from the scalp exit site of the cisternal tube. All of the five cases had obtained good recovery at three months after the operation. These results show that, although this method involves a risk of infection, it has the advantage of easiness and convenience over conventional methods. Though further improvement of this method is required, this preliminary stage is potentially useful for delivering not only nicardipine, but also for other drugs which may be used in intrathecal administration therapy.

Aged↗
PubMed2001

[Antitumor effect of the plant alkaloid preparation, cepharanthin].

The antitumor effect of cepharanthin (CR), a biscoclaurine alkaloid, was examined as to its direct action on tumor cells and inhibitory action on angiogenesis in tumors. The effect of CR on in vitro invasion by murine RL-[symbol: see text] 1 leukemia cells and Colon 26 tumor cells was studied using a biocoat matrigel invasion chamber. One hundred micrograms/ml of CR inhibited tumor cell invasion. Early induction of apoptosis was assayed by the binding of annexin V and phosphatidylserine (PS) in the cellular membrane CR (10 and 100 micrograms/ml) induced apoptosis in human Daudi and Raji B lymphoblastoid cells. Treatment with CR (1 and 10 micrograms/ml) also inhibited the in vitro growth of Daudi and Raji cells. Ten micrograms/ml of CR also inhibited the growth of human umbilical vein endothelial cells (HUVEC) and human dermal microvascular endothelial cells (HMVEC). These results indicate that CR has diversified antitumor functions, i.e., an enhancement of a sequential immune mechanism, a direct cytotoxic effect and inhibitory action of angiogenesis in tumors.

Alkaloids↗
PubMed2001

[Combination of acute normovolemic hemodilution technique with preoperative autologous blood donation prevented allogeneic blood transfusion against 4000 g surgical blood loss in a patient undergoing left partial nephrectomy].

A 41-year-old male patient with well-controlled hypertension underwent a partial nephrectomy under total intravenous anesthesia with propofol, fentanyl and ketamine. To avoid allogeneic blood transfusion, preoperative autologous blood donation (400 g) a week before the surgery and acute normovolemic hemodilution (800 g) after induction of anesthesia were performed. As surgical blood loss was more than 4000 g, blood hemoglobin (Hb) level decreased to 6.4 g.dl-1. However, as intraoperative hemodynamics was relatively stable with no ischemic changes in ECG and arterial blood gas analysis did not show metabolic acidosis, autologous blood transfusion was withheld till hemostasis had been done. After returning the autologous blood, Hb increased to 9.4 g.dl-1. On the 2nd postoperative day, Hb decreased to 7.6 g.dl-1. As the patient's vital signs did not show any severe complications, blood transfusion was not performed. Then, the Hb level increased gradually to 13.9 g.dl-1, 3 month later without allogenic blood transfusion. In addition, any postoperative complications by low Hb level were not recognized so far. This case suggests that combination of autologous transfusion techniques may be effective to avoid allogeneic blood transfusion even against massive hemorrhage. However, to avoid disadvantage of these technique, we should always evaluate preoperative patient conditions.

Adult↗
PubMed2001

[Spontaneous intracranial hypotension complicating subdural hematoma: unilateral oculomotor nerve palsy caused by epidural blood patch].

We report a case of a 41-year-old man with a 1-month history of postural headache due to spontaneous intracranial hypotension (SIH). His MRI revealed bilateral chronic subdural hematoma (CSH) and diffuse dural enhancement after gadolinium infusion. Indium-111 radionuclide cisternography revealed a CSF leak from the cervico-thoracic junction and rapid accumulation of radioisotope in the bladder. Postural headache failed to resolve with prolonged bed rest. The patient became restless and suffered recent memory disturbance. We therefore decided to treat the CSF leak with an epidural blood patch. After the procedure, the patient's headache resolved completely. However one day later, left oculomotor nerve palsy developed. MRI revealed enlargement of the left CSH with mass effect and midline shift. After hematoma drainage, the patient became alert and oculomotor palsy recovered gradually. To treat cases of CSH with SIH, the best method is to repair the CSF leakage and treat subdural hematoma at the same time. If the patient shows depressed consciousness, we recommend initial drainage of the subdural hematoma, because, following the repair of CSF leakage, mass effect such as uncal herniation may occur.

Adult↗
PubMed2001

[Intratumoral administration of biological preparations--recommendation for integrative medicine].

The antitumor effect of biological preparations was examined in a double grafted tumor system. PSK is a hot water extract of cultured mycelia from Coliolus versicolor. Its protein content is about 38% and the main glycoside portion of PSK is beta-D-glucan. Lentinan is purified from fruit bodies of Lentinus edodes and is a beta-1, 3-glucan. Cepharanthin is an extract from the root of Stephania cepharantha HAYATA, consisting of 4 kinds of biscoclaurine alkaloids. TAHEEBO tea is a hot water extract of Tabebuia avellanedae, the active ingredient of which is naphthoquinones. If protein-bound polysaccharides were to be used in Western medicine, these polysaccharides would be purified, but purified beta-glucan loses its beneficial effects. Similarly, when raw Cepharanthin is purified to isolate its active ingredient (an alkaloid cepharanthine), its anti-tumor effect is weakened. Clear IAP induction was observed in serum of mice treated with extracts of Coliolus versicolor and Stephania cepharantha. However, IAP induction was not observed in the serum of mice treated with purified beta-glucan or purified alkaloid. This suggests that macrophages may recognize extracts but not purified substances. In Western medicine, purified substances with known chemical structures are recognized as drugs, but overdoses of these drugs are toxic to the body, thus adverse reactions are always an issue. In Chinese medicine, mixtures containing several crude drugs are recognized as drugs, whose active ingredients are not identified. In integrative medicine, drugs are extracts that contain active ingredients with known structures and functions. We propose a Japanese version of integrative medicine which is neither Western nor Chinese.

Animals↗
PubMed2000

[Efficacy of antibiotic prophylaxis in clean neurosurgical operations: a comparison of seven-day versus one-day administration].

We compared seven-day and one-day administration of antibiotics as prophylaxis in clean neurosurgical operations. A total of 175 patients were examined. Seven-day administration (protocol A) was studied retrospectively from May 1997 to May 1998 in 87 patients of 46 craniotomies and 41 burr hole operations. One-day administration (protocol B) was studied prospectively from June 1998 to July 1999 in 88 patients of 39 craniotomies and 49 burr hole operations. Protocol A received 1.5 g of sulbactam/ampicillin = 1:2 (SBT/ABPC) preoperatively, and further doses were continued at 12-hour intervals for seven days after the operation. Protocol B received 1.5 g of SBT/ABPC preoperatively and intraoperative additional antibiotics were administered at 5-hour intervals, and only one single dose was administered after the operation. In both of the protocols, 60 mg of tobramycin was mixed with 500 ml of saline for irrigation of operative fields. No postoperative infection occurred in either of the two protocols. We conclude that one-day administration of prophylactic antibiotics is enough to prevent postoperative infections in clean neurosurgical operations.

Ampicillin↗
PubMed1999

A Combined X-Ray Photoelectron and Auger Electron Spectroscopic Study of Cesium in Variable-Charge Montmorillonites.

A combined X-ray photoelectron and Auger electron spectroscopic investigation of sorption and characterization of bonding states of Cs in montmorillonite (M) and in four reduced-charge montmorillonites (RCMs) were carried out. The nondestructive analysis of sorption of Cs in variable-charge montmorillonites obtained by XPS is consistent within 4-8% to those obtained by solution analysis using AAS. The core-level Cs 3d5/2 photoelectron binding energy was observed to be enhanced with the reduction of electron population from higher to lower charge montmorillonite. The charge potential model has been used to interpret such core-level short-range chemical shifts. However, a larger shift in the Auger Cs-M4N4,5N4,5 line was observed and Cs-Auger kinetic energy was found to decrease from higher charge RCM to lower charge RCM, which may be attributed to the effect of extra-atomic relaxation from surrounding oxygen atoms; this effect implies that the flow of electronic charge to the Cs ion is larger for higher charge RCM than for lower charge RCM. However, this effect is enhanced by the extra contribution of Li that has migrated. A comparison of Cs 3d binding energies and Cs-Auger kinetic energies in a two-dimensional chemical state plot indicates multiple bonding states of Cs in variable-charge montmorillonites. The extra-atomic relaxation energy (DeltaEr) value of each of the Cs-montmorillonites was unique, which indicates that this is dependent on the chemical environment and on the availability of electron density in montmorillonites. Also, the binding energy value of Cs 3d5/2 was found to be nearer to CsOH than to CsCl, which reflects that the bonding state of Cs is not as ionic as CsCl. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

A case of adult moyamoya disease showing progressive angiopathy on cerebral angiography.

In moyamoya disease, progression of carotid occlusive lesion in an adult patient is very rare. We report a case of adult moyamoya disease with acute angiographical stage progression and hemodynamic deterioration. A 56-year-old female complaining of left motor weakness visited our department. On MRI, infarct lesion was found in the right white matter. On cerebral angiography, occlusive lesions in the bilateral internal carotid arterial siphons and moyamoya vessels were found. The right side was stage V and the left side was stage III. On IMP-SPECT, decreased cerebral hemodynamic reserve of the right cerebral hemisphere was found. In this patient, right STA-MCA anastomosis was performed. After operation, she became possible to walk and discharged to home. Five months after operation, good collateral formation and improvement of hemodynamic reserve in the right hemisphere were found. However, on left carotid arteriography, the anterior and middle cerebral arteries were only slightly imaged, and the disease state progressed to stage IV. In addition, decreased blood flow and hemodynamic reserve were appeared in the left hemisphere.

Brain↗
PubMed1999

Is total body weight an appropriate predictor for propofol maintenance dose?

BACKGROUND: Infusion rate of propofol during anaesthesia is usually based on total body weight. In this study, we have determined the relationship between total body weight and plasma propofol levels when the infusion rate was based on total body weight. METHODS: Sixty patients undergoing elective surgery were studied. Anaesthesia was induced with propofol 1 mg x kg(-1), ketamine 1 mg x kg(-1) and fentanyl 2 microg x kg(-1), and maintained with propofol 5 mg x kg(-1) x h(-1), ketamine 0.5-1 mg x kg(1) x h(-1) and fentanyl 5-15 microg x kg(-1). Propofol infusion rate did not change during anaesthesia, and infusion was terminated at the end of surgery. Immediately prior to termination of the propofol infusion, arterial blood (5 ml) was collected to measure plasma level of propofol by a high-performance liquid chromatography equipped with electrochemical detection. RESULTS: There was a significant correlation between plasma propofol and total body weight (r=0.646, P<0.001). Plasma propofol concentration also correlated with infusion rate, corrected to lean body mass (r=0.527, P<0.001). CONCLUSION: During a fixed infusion rate, plasma propofol concentration may be dependent on total body weight.

Anesthetics, Dissociative↗
PubMed1999

A high-Mr glycoprotein fraction from cow's milk potent in inhibiting replication of human rotavirus in vitro.

Rotavirus is the major cause of infectious diarrhea in infants and young children all over the world. We have found that a high-M(r) glycoprotein fraction from cow's milk is potent in inhibiting replication of human rotaviruses in vitro. Since the activity seems to be unique and specific, this fraction may be useful as a novel agent for treatment or prevention of rotavirus diarrhea.

Animals↗
PubMed1999

Expression of genes for proinflammatory cytokines in alveolar macrophages during propofol and isoflurane anesthesia.

UNLABELLED: Anesthesia and surgery induce macrophage aggregation and neutrophil influx, responses that characterize an inflammatory reaction in the distal airway. We thus evaluated the time-dependent expression of genes for proinflammatory cytokines during propofol and isoflurane anesthesia. We studied patients anesthetized with propofol (n = 20) or isoflurane (n = 20). Alveolar macrophages were harvested by bronchoalveolar lavage immediately, 2, 4, and 6 h after induction of anesthesia, and at the end of surgery. RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. Expression of interleukin-1beta (IL-1beta), IL-6, IL-8, interferon gamma, and tumor necrosis factor-alpha was measured by semiquantitative polymerase chain reaction using beta-actin as an internal standard. We observed two 10-fold increases in gene expression of all proinflammatory cytokines except IL-6. The increases in IL-8 and interferon gamma were 1.5-3 times greater during isoflurane than propofol anesthesia. Expression of the genes for IL-1beta and tumor necrosis factor-alpha was similar with each anesthetic. Our data thus indicate that the pulmonary inflammatory response accompanying anesthesia and surgery is accompanied by the expression of proinflammatory cytokines, and that this expression was in some cases greater during isoflurane than propofol anesthesia. IMPLICATIONS: Gene expression of proinflammatory cytokines in alveolar macrophages increased significantly over time. The increases were greater during isoflurane than propofol anesthesia, suggesting that inflammatory responses at transcriptional levels in alveolar macrophages are modulated by the type and duration of anesthesia.

Anesthesia↗
PubMed1998

Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis.

We have isolated a novel type of natural tumoricidal product from the basidiomycete strain, Agaricus blazei Murill. Using the double-grafted tumor system in Balb/c mice, treatment of the primary tumor with an acid-treated fraction (ATF) obtained from the fruit bodies resulted in infiltration of the distant tumor by natural killer (NK) cells with marked tumoricidal activity. As shown by electrophoresis and DNA fragmentation assay, the ATF also directly inhibited tumor cell growth in vitro by inducing apoptotic processing; this apoptotic effect was also demonstrated by increased expression of the Apo2.7 antigen on the mitochondrial membranes of tumor cells, as shown by flow-cytometric analysis. The ATF had no effect on normal mouse splenic or interleukin-2-treated splenic mononuclear cells, indicating that it is selectively cytotoxic for the tumor cells. Cell-cycle analysis demonstrated that ATF induced the loss of S phase in MethA tumor cells, but did not affect normal splenic mononuclear cells, which were mainly in the G0G1 phase. Various chromatofocussing purification steps and NMR analysis showed the tumoricidal activity to be chiefly present in fractions containing (1-->4)-alpha-D-glucan and (1-->6)-beta-D-glucan, present in a ratio of approximately 1:2 in the ATF (molecular mass 170 kDa), while the final purified fraction, HM3-G (molecular mass 380 kDa), with the highest tumoricidal activity, consisted of more than 90% glucose, the main component being (1-->4)-alpha-D-glucan with (1-->6)-beta branching, in the ratio of approximately 4:1.

Agaricus↗
PubMed1998

Interleukin-15 effectively potentiates the in vitro tumor-specific activity and proliferation of peripheral blood gammadeltaT cells isolated from glioblastoma patients.

GammadeltaT cells play a regulatory role in both primary and metastatic tumor growth in humans. The mechanisms responsible for the activation and proliferation of circulating gammadeltaT cells should be fully understood prior to their adoptive transfer to cancer patients. We have examined in vitro functional effects of interleukin-15 (IL-15) on highly purified gammadeltaT cells isolated from glioblastoma patients. GammadeltaT cells constitutively express the heterotrimeric IL-2 receptor (IL-2R) alpha betagamma, but the levels of IL-2Rbeta or gamma expression were not increased by incubation with saturating amounts of IL-15. IL-15 was shown to induce a maximal gammadeltaT cell proliferation, although at much higher concentrations (at least 2000 U/ml) than IL-2 (100 U/ml). Submaximal concentrations of IL-15 plus low concentrations of IL-2 produced an additive proliferative response. In contrast to the IL-2-induced response, this activity was completely or partially abrogated by anti-IL-2Rbeta, or anti-IL-2Rgamma antibodies, but not by anti-IL-2R alpha antibodies. Incubation of gammadeltaT cells in the presence of IL-15 resulted not only in the appearance of NK and LAK activity, but also in specific autologous tumor cell killing activity, an additive effect being seen with IL-15 and IL-2. This IL-15-induced tumor-specific activity could be significantly blocked by anti-IL-2Rgamma and anti-IL-2R-beta mAb, but not by anti-IL-2R alpha mAb. Thus, in contrast to IL-2, IL-15 activates tumor-specific gammadeltaT cells through the components of IL-2Rbeta and IL-2Rgamma, but not IL-2R alpha. These enhanced in vitro tumor-specific and proliferative responses of gammadeltaT cells seen with IL-15 suggest a rational adjuvant imunotherapeutic use of gammadeltaT cells in cancer patients.

Antibodies, Monoclonal↗
PubMed1998

The use of BRM-activated killer cells in adoptive immunotherapy: a pilot study with nine advanced cancer patients.

Adoptive immunotherapy using MHC-nonrestricted-lymphocytes, peripheral blood gammadelta T cells and NK cells was devised. Peripheral blood mononuclear cells (3 x 10(7)) were selected by immobilization to anti-CD3 monoclonal antibody for 4 days and cultured for 2 weeks in the presence of IL-2. Thereafter they were reactivated by 500 U/ml of IFN-alpha and 1000 U/ml of IL-2 for 1 hour. Enhancement of NK and LAK activities was confirmed. Peripheral blood gammadelta T cells proliferated in response to immobilized anti-CD3 antibody (3% to 30%). Approximately 6 x 10(9) BRM-activated killer (BAK) cells composed of CD56+ gammadelta T cells and CD56+ NK cells, were dispensed to cancer patients via intravenous drip infusion. Nine patients were treated with BAK cells every 2 weeks or every month on an outpatient basis. During the course of adoptive immunotherapy, the crossed affinity immunoelectrophoresis (CAIE) pattern of serum immunosuppressive acidic protein (IAP) was analysed. Both the production and glycosylation pattern of IAP is changed in response to tumor enlargement and may therefore act as a marker of the disease progression. During the course of BAK therapy, the glycosylation IAP pattern of 6 patients changed from tumor (T) to normal (N). In addition, the performance status of all patients was maintained at 90-100% of the Karnofsky scale and any side effects including fever were not observed during treatments with BAK cells. Moreover, the overall quality of life (QOL) of the patients, scored at the Face scale was favorable. In addition, blood levels of activated gammadelta T cells producing IFN-gamma were assayed as an indication marker of BAK therapy. The normal range of IFN-gamma producing gammadelta T cells comprised 6.9 +/- 0.9% of peripheral blood mononuclear cells (PBMC), according to a single cell FACScan analyses of PBMCs derived from normal individuals. IFN-gamma producing gammadelta T cells of Patients No. 8 and 9, who received extensive chemotherapy before initiation of BAK therapy, comprised only 0.2% and 2% of PBMC, respectively. These patients died 3 and 6 months after beginning BAK therapy. Peripheral blood gammadelta T cells of Patients Nos. 1-7 proliferated in response to immobilized anti-CD3 antibody and the frequency of IFN-gamma producing gammadelta T cells in PBMC preparation of these patients were over 3% before initiation of BAK therapy. Since our data show a positive correlation between survival time and initial gammadelta T cell counts, a low frequency of these cells may contraindicate BAK therapy.

Adult↗
PubMed1998

Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted tumor system in mice.

The antitumor effect of extracts obtained from the fruit body of Agaricus blazei Murill was examined in a double-grafted tumor system, in which BALB/c mice received simultaneous intradermal injections of Meth-A tumor cells in both the right (10(6) cells) and left flank (2 x 10(5) cells), and were then injected with 5 mg of extracts of A. blazei in the right tumor on days 3, 4 and 5. Intratumoral administration of ethanol-soluble (Fraction 1), water-ethanol-soluble (Fraction 2), ammonium oxalate-soluble (Fraction 3) and ammonium oxalate-insoluble (Fraction 4) fractions resulted in inhibition of tumor growth, with Fraction 3 showing the most tumoricidal activity, producing regression of the right tumor and inhibition of growth of the left, non-injected tumor. The maximum effect was obtained using 0.5 mg of Fraction 3 and this amount was used in subsequent experiments. The antitumor effect of intratumorally administered Fraction 3 was enhanced by oral ad lib administration of feed containing 0.083% of Fraction 3. When immunized spleen cells from mice that had been cured by intratumoral administration of 0.5 mg of Fraction 3 were directly injected (2 x 10(7) cells/mouse) into the Meth-A tumor, tumor growth was inhibited. The tumor cells on day 7 from the Fraction 3-treated right tumor and from the left tumor were cultured for 24 h and their culture supernatants were assayed for neutrophil or macrophage chemotactic activity. Significant macrophage chemotactic factor activity was detected in the culture media from the left tumor tissue. Serum levels of immunosuppressive acidic protein (IAP), produced by activated macrophages and neutrophils, increased transiently soon after intradermal injection of 0.5 mg of Fraction 3. These results suggest that regression of the left non-injected tumor was due to an immune reaction, involving induction of cytotoxic cells in the spleen, and the release of chemotactic factors in the distant tumor.

Adoptive Transfer↗