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Biomedical subjects

F Abe

Publications and source records attributed to F Abe.

At least 217 records · Page 12Linked to original sources
PubMed1989

Chemoimmunotherapy with cyclophosphamide and bestatin in experimental metastasis in mice.

Bestatin has significant therapeutic activity (even following oral administration) for the treatment of metastatic disease, an activity which is limited by tumor burden. Therefore, the therapeutic potential of bestatin was examined in combination with chemotherapy to determine if there is additive activity for heavy tumor burdens. Bestatin significantly increased therapeutic activity and decreased the myelotoxicity of cyclophosphamide following a single injection of cyclophosphamide or split daily doses. In immune function studies, in tumor-bearing animals, bestatin increased the number of colony-forming units (granulocyte-macrophage) (CFU) and alveolar macrophage tumoricidal activity. However, when bestatin was combined with cyclophosphamide, which depressed bone marrow and macrophage activity, it did not show apparent augmentation of macrophage and NK cell activity, but did significantly increase bone marrow CFU activity. Thus, in combined chemoimmunotherapy, bestatin appears to enhance therapeutic activity by accelerating the recovery of hematopoiesis. We suggest, therefore, that a combination chemotherapy protocol, with oral bestatin, may facilitate myelorestoration following aggressive chemotherapy. The majority of biological response modifiers require parental administration; thus, the identification of an orally active, synthetic immunoaugmenting agent with a defined receptor is of particular interest.

Adjuvants, Immunologic↗
PubMed1989

Pharmacokinetics of bestatin and oral activity for treatment of experimental metastases.

Bestatin is a low molecular weight aminopeptidase inhibitor originally isolated from culture filtrates of Streptomyces olivoreticuli. The serum pharmacokinetics in mice are dependent on route of administration, with a short t1/2 (1.69 min t1/2 alpha and 12.8 min t1/2 beta), but a high initial serum level following i.v. administration. When administered via the i.p., s.c., i.m., or p.o. routes of administration, bestatin had serum t1/2 beta s of 8.56, 16.91, 19.25, or 15.4 min, respectively. The maximum area under the curve (concentration X time) occurred following i.v. and i.m. administration, with a lower level following p.o. or i.p. administration. Bestatin had therapeutic activity for experimental metastases, not only following i.v., i.p., and i.m. routes of administration but also following oral administration. Because of its brief serum t1/2, bestatin's therapeutic activity depends on aggressive (either daily or twice daily injection, especially following p.o. administration) and high-dose administration. Thus, the rate-limiting aspect of bestatin's therapeutic activity appears to be associated with its pharmacokinetics.

Administration, Oral↗
PubMed1989

Inhibition of tumor cell invasion by ubenimex (bestatin) in vitro.

We have investigated the effect of the immunomodulator ubenimex (bestatin) on tumor cell invasion of reconstituted basement membrane (Matrigel). The invasion of B16-BL6 melanoma cells and Lewis lung carcinoma (3LL) cells into Matrigel-coated filters was inhibited by the presence of bestatin in a concentration-dependent manner. The pretreatment of either tumor cells or Matrigel with bestatin, however, had little effect on the invasion of tumor cells. Since bestatin was found to inhibit amino-peptidase in addition to its immunomodulating activities, the inhibition of tumor invasion by bestatin is likely to be associated with the action as an enzyme inhibitor. Other aminopeptidase inhibitors, arphamenine B and amastatin A, could also inhibit tumor cell invasion into Matrigel. Bestatin inhibited hydrolyzing activities towards substrates of aminopeptidases in B16-BL6 melanoma cells. However, bestatin did not have any effect on the haptotactic migration and adhesion of tumor cells to the substrates. These results indicated that bestatin may inhibit tumor cell invasion through a mechanism involving its inhibitory action on aminopeptidases in tumor cells.

Aminopeptidases↗
PubMed1989

Transition of starving Dictyostelium cells to differentiation phase at a particular position of the cell cycle.

The relationship between proliferation and differentiation in Dictyostelium discoideum Ax-2 was analyzed with reference to the cell-cycle position at the onset of starvation, using cells synchronized by temperature shift (11.5 degrees C-22.0 degrees C). To examine how far Ax-2 cells at any particular phase of the cell cycle are able to progress through the cycle in response to nutritional deprivation, we measured temporal changes in cell number and nuclearity after starvation. Nuclear DNA synthesis in synchronously developing cells was also monitored by pulse-labeling with [methyl-3H]thymidine. Increase in cell number and subsequent DNA synthesis occurred in cells just before mitosis (referred to as T0.5 cells and T1 cells; 0.5 h and 1 h after the shift-up from 11.5 degrees C to 22.0 degrees C respectively), but not in T3, T5, or T7 cells. When T1 cells were incubated for 6 h in the absence of external nutrients, they (T1 + 6 cells) exhibited developmental features similar to T7 cells, which most rapidly acquired chemotactic sensitivity to 3',5'-cyclic adenosine monophosphate (cAMP) and EDTA-resistant cohesiveness after starvation. Thus, it is quite likely that Ax-2 cells may progress through the cell cycle to a particular point (possibly the cell-cycle position of T7 cells), irrespective of the presence or absence of nutrients, and enter the differentiation phase from this point under conditions of nutritional deprivation. There was no difference in the ratio of prestalk to prespore cells in migratory pseudoplasmodia derived from cells that had been starved at other cell-cycle positions.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Cycle↗
PubMed1989

Alterations in fructosamine and glycated albumin levels during childhood.

Age-related changes in the blood concentrations of glycated proteins during childhood and adolescence were examined by measuring the blood fructosamine (FA), glycated albumin (GA), glucose levels and total serum protein levels in 611 healthy children (325 boys and 286 girls) aged 0-18 years old. These levels were compared with those of 130 healthy adults. GA was measured by a newly developed, highly precise method of high-performance liquid chromatography (inter-assay coefficient of variation, 4.9%). The FA values of all groups of up to 15 years old (grouped in two year age brackets) were significantly lower than those of adults. The mean serum concentrations of GA in infants up to four years old were also significantly lower than in adults. A slight but statistically significant positive correlation was found between age and values of FA (r = 0.36, P less than 0.001), but not of GA (r = 0.04). Levels of total serum proteins showed a positive correlation with those of FA (r = 0.47, P less than 0.001) but a weak correlation with those of GA (r = 0.29). These results suggest that age should be taken into account when the FA levels of children and the GA values of infants are evaluated.

Adolescent↗
PubMed1989

Effects of deoxyspergualin on hematopoiesis: studies of murine hematopoietic progenitor cell and peripheral blood cell levels.

The effect of a novel immunosuppressive agent, deoxyspergualin (DSG), on hematopoiesis in mice was studied with measurements of peripheral blood counts and assays of granulocyte-monocyte colony-forming cells (cfu-C) and spleen colony-forming cells (cfu-S) in bone marrow, during and after successive intraperitoneal administration of DSG. When DSG was administered at a strong immunosuppressive dose of 6.25 mg/kg daily for 15 days, mice developed significantly decreased peripheral blood counts and decreased bone marrow cells (BMC) during administration. After the completion of DSG administration a marked rebound in leukocytosis was observed and BMC returned to normal. In contrast, total cfu-C in the femur significantly increased during the DSG administration, and subsequently returned to normal. Moreover, total cfu-S in the femur were normally sustained in contrast with a decrease of BMC during the DSG administration. These findings suggest that DSG does not show generalized overt cytotoxicity against hematopoietic stem cells and freezes the ability of the stem cell in the proliferation or the differentiation.

Animals↗
PubMed1989

In vitro immunosuppressive properties of spergualins to murine T cell response.

Deoxyspergualin has strong immunosuppressive activity in animals. However, it shows less in vitro immunosuppressive activity at the therapeutic concentration used for in vivo administration. Recently, we reported that there are some technical problems with in vitro experiments. In this report, the effects of spergualins were examined under in vitro conditions which excluded these problems, and compared with cyclosporine A (CYA). Spergualins have suppressive effects on mixed lymphocyte response (MLR) and cytotoxic T lymphocyte induction. Furthermore, interleukin-2 (IL-2) induced proliferation of concanavalin A blasts and CTLL-2 were inhibited at low concentration. However, spergualins have little effect in the early stage of MLR or the mitogen response. These results suggest that spergualins act on the proliferation and differentiation of T cells which respond to growth factors, such as IL-2.

Animals↗
PubMed1989

Protective, restorative, and therapeutic properties of recombinant colony-stimulating factors.

Pretreatment of mice with recombinant murine (rM) colony-stimulating factor-granulocyte-macrophage (CSF-gm) or recombinant human (rH) CSF-g provides partial protection from the lethal effects of ionizing radiation or the alkylating agent cyclophosphamide (CTX). In addition, these agents can significantly prolong survival if administered following lethal doses of irradiation or CTX. To induce protective activity, cytokines were injected 20 hours before lethal irradiation or CTX administration. To accelerate recovery from lethal irradiation, the cytokines must be administered shortly following irradiation, and the induction of maximal levels of activity is dependent on chronic administration. In contrast, because of their longer half-lives, accelerated recovery from alkylating agents requires a delay of at least 24 to 48 hours to allow complete clearance of CTX before administration of a CSF. Studies quantitating peripheral blood leukocytes and bone marrow cellularity as well as colony-forming units per culture (CFU-C) frequency and CFU-C per femur revealed a significant correlation between these parameters and the ability to survive lethal irradiation. This is a US government work. There are no restrictions on its use.

Animals↗
PubMed1989

[Long-term survival of a patient with pseudoaneurysm of the left ventricle following myocardial infarction].

A 76-year-old man had an extensively calcified left ventricular pseudoaneurysm which was a sequela of acute myocardial infarction suffered 22 years ago. He experienced acute anterolateral myocardial infarction in January 1964. In March 1964, the presence of a left ventricular aneurysm was suspected by chest radiography and fluoroscopy. He was, however, in good health since then. In April 1986, when he was admitted for treatment of acute bronchitis, a large calcified density was found in the left ventricular region on chest radiography. The electrocardiogram was compatible with an old anterolateral myocardial infarction. Two-dimensional echocardiography showed an immobile portion of the left ventricle which contained "moya-moya" (sluggish, smoky) echoes. A saccular aneurysm of the left ventricle was confirmed by radioisotope cardiac pool scans, reconstruction CT and left ventriculography. Due to the poor general condition of the patient, we followed his course without surgery. He died in October 1986. At autopsy, the pseudoaneurysm was markedly calcified, and its wall was adherent to the parietal pericardium. Histologically, the pseudoaneurysmal structure turned out to be a pseudoaneurysm since the saccular wall contained only scar tissue but no myocardial cells. This is a very rare case of a patient with a left ventricular pseudoaneurysm who survived for 22 years after its occurrence.

Aged↗
PubMed1988

Protective, restorative, and therapeutic properties of recombinant human IL-1 in rodent models.

Human rIL-1 alpha and -1 beta are shown to increase significantly the CFU-culture activity in the spleen as well as at other sites after i.v. or i.p. administration. IL-1 can also significantly increase survival and can "rescue" a number of animals if administered either before or after lethal doses of cyclophosphamide or gamma-irradiation. The protective and reconstitutive activities of the rIL-1 are shown to correlate with increased CFU-culture frequency and total number, as well as increased cellularity in the bone marrow and peripheral blood, suggesting that this is one of their mechanisms of action. The sequence and timing of administration of human rIL-1 is critical for the protection or rescue of animals receiving DNA-damaging agents; maximal activity is achieved when IL-1 is given 20 h before insult or 48 h after alkylating agent administration. Minimal therapeutic activity is observed with IL-1 as a single agent for the treatment of metastatic disease compared with other biologic response modifiers including IFN-gamma.

Animals↗
PubMed1988

High-performance liquid chromatographic assay of serum glycated albumin.

A method for determination of serum glycated albumin by high-performance liquid chromatography is presented. The system involves anion exchange chromatography to separate albumin and consecutive boronate affinity chromatography to separate glycated and nonglycated albumin. The method is rapid (20 min), precise (coefficient of variation, 0.7-4.9%), requires only a small sample (5 microliters), and can be automated. Assay of glycated albumin by this method is not influenced by the protein concentration of the sample or the presence of glucose. The variation in glycated albumin values in consecutive samples obtained within a day from diabetic patients (coefficient of variation, 2.02 +/- 0.65%) was significantly smaller (p less than 0.001) than that of values for fructosamine (coefficient of variation, 4.33 +/- 2.0%). The values of glycated albumin in normal subjects (20.2 +/- 1.6%) were clearly less than those in diabetic patients [39.6 +/- 5.4% in 40 Type 1 (insulin-dependent) and 39.4 +/- 5.9% in 25 Type 2 (non-insulin-dependent) patients]. The serum glycated albumin level was well correlated with HbA1c in 65 diabetic patients (r = 0.60). Because the life span of albumin in the circulation is short, measurement of glycated albumin should be useful as a short-term index of glycaemic control.

Biomarkers↗
PubMed1988

Experimental candidiasis associated with liver injury. Role of transferrin.

In an attempt to perform a further investigation on the proposal that an increasing susceptibility to Candida infection in liver injury may be related to unsaturated transferrin level (UIBC) and/or to a total amount of transferrin represented by TIBC, we conducted experimental candidiasis using mice with galactosamine-induced liver injury and investigated the effect of preadministration of transferrin prior to inoculation of Candida albicans. Final mortality was 10% in the mice without liver injury and without transferrin (Group 1) and ones with liver injury and with transferrin (Group 3). By contrast a 50% mortality was given in one only with liver injury (Group 2). The TIBCs in Groups 1 and 3 were significantly higher than that in Group 2. The UIBCs in Groups 2 and 3, although there was no significant difference between them, were significantly lower than that in Group 1. This study confirmed that transferrin (TIBC) may have a direct deterring effect on systemic Candida infection and the decreased TIBC in the liver injury enhances the growth of C. albicans.

Animals↗
PubMed1988

Biological activities of deoxyspergualin in autoimmune disease mice.

An assessment of the prophylactic and ameliorative effects of deoxyspergualin (NKT-01), an immunosuppressive agent, was carried out in male MRL/MpJ-lpr/lpr (MRL/1) mice which spontaneously develop lupus-like lesions. When NKT-01 was administered ip daily from the age of either 8 or 19 weeks, diseases such as massive lymphadenopathy, circulating anti-DNA antibody and lupus nephritis were markedly suppressed. The primary response to lipopolysaccharide was significantly reduced in MRL/1 mice administered NKT-01 but the response to sheep red blood cells was not affected. The ability of spleen cells to release interleukins 2 and 3 with or without mitogen was significantly enhanced in mice receiving NKT-01. These findings demonstrate that NKT-01 has therapeutic activity against the development of spontaneous disease in MRL/1 mice.

Animals↗