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Y Saeki

Publications and source records attributed to Y Saeki.

At least 199 records · Page 11Linked to original sources
PubMed1987

Analysis of the idiotypic network in tumor immunity.

Herein we have analyzed the expression of idiotopes associated with a monoclonal anti-tumor-associated antigen (TAA) antibody in DBA/2 mice which have progressively growing tumors or resist tumor growth. A panel of eight monoclonal antiidiotypic antibodies raised against a monoclonal antibody which reacts with a mouse mammary tumor virus cross-reactive qp52 envelope protein (TAA) of the L1210/GZL lymphoma was used to measure the expression of idiotopes in sera from different treatment groups. Significant correlations between the expression of certain idiotopes and the growth of the tumor or the establishment of anti-tumor immunity are seen. 1) Idiotypes detected by anti-idiotype D11 are high in anti-idiotype immunized progressor or tumor-susceptible mice and low or absent in regressor mice, i.e., the mice immunized with the protective 2F10 anti-idiotype; 2) the 3A4-detected idiotypes are less frequent or absent in irradiated tumor-immunized regressor mice than in untreated mice challenged with live tumor or progressor mice; 3) no difference in the anti-TAA titers is seen in mice in which the tumor growth is inhibited and in mice in which the tumor grows; 4) no difference in 11C1 idiotype + anti-TAA titer was observed between regressor and progressor mice; and 5) mice with normal or accelerated tumor growth have higher titers of idiotypes detected by a polyclonal anti-idiotype. These findings provide evidence for a regulatory idiotype network induced by the growing L1210/GZL tumor or by anti-idiotypic immunization. The titer of anti-TAA antibody does not correlate with the biology of tumor growth, but certain idiotopes correlate with either progressive or regressive tumor behavior. Therefore, the target of the idiotype regulation is likely to be anti-tumor T effector cells. Effective idiotype therapy of tumors must deal with the complexity of idiotype regulation induced by the tumor itself and is unlikely to be successful if anti-idiotypes are used only as internal mimicry of a TAA.

Animals↗
PubMed1987

Tumor-specific idiotype vaccines. III. Induction of T helper cells by anti-idiotype and tumor cells.

In a previous report, we have demonstrated the induction of tumor-specific immunity by monoclonal anti-idiotype antibodies generated against a monoclonal anti-tumor antibody, 11C1, that also cross-reacts with mouse mammary tumor virus envelope glycoprotein gp52. Also, we showed that whereas one anti-idiotype antibody, 2F10, could induce protective immunity, another anti-idiotype antibody, 3A4, induced nonprotective immunity. Here we demonstrated the existence of T helper cells which recognize anti-idiotypes that exert differential controls on tumor growth. The qualitative nature of idiotype recognizing T cells generated in response to 2F10, 3A4, irradiated tumor, and progressively growing tumor was compared. The reactivity pattern of idiotype recognizing T cells obtained from 2F10 and irradiated tumor immunized mice were similar in nature in the sense that Lyt-2- T cells obtained from these immunized mice responded to both 2F10 and 3A4 as antigen, although T cells from tumor immunized mice responded better to 3A4 antigen. On the other hand, the idiotype-recognizing T cells obtained from 3A4-immunized mice showed a similar reactivity pattern to T cells isolated from mice during the early phase of tumor growth (within day 4 to 5 after the inoculation of 10(4) live tumor cells). Lyt-2- T cells isolated from mice immunized with 3A4 or during the early phase of tumor growth responded only to 3A4 antigen. The inability of Lyt-2- T cells, isolated from 4- to 5-day-old tumor in mice, to cooperate with 2F10-TNP is not due to the absence of 2F10 idiotype recognizing T cells as 2F10 id recognizing T cells are present when examined at the precursor level. These data on the idiotype specificity of T helper cells show a correlation with the presence of anti-tumor immunity. This information will help in the design and application of idiotype vaccine in tumor immunotherapy.

Animals↗
PubMed1987

Tumor-specific idiotype vaccines. II. Analysis of the tumor-related network response induced by the tumor and by internal image antigens (Ab2 beta).

In this study the tumor-specific immuneresponse induced by irradiated tumor cells (L1210/GZL) and by anti-idiotype antibodies was analyzed. The anti-idiotype antibodies (Ab2) were made against the paratope of a monoclonal antitumor antibody (11C1) that recognizes a tumor-associated antigen which cross-reacts with the mouse mammary tumor virus-encoded envelope glycoprotein 52. Two Ab2, 2F10 and 3A4, induced idiotypes expressed by the monoclonal antitumor antibodies 11C1 and 2B2. Cytotoxic T cells, generated by immunization with irradiated tumor cells, lyse 2F10 and 3A4 hybridoma cells. Furthermore, immunization with Ab2 induces tumor-specific cytotoxic T lymphocytes. The frequency of tumor-reactive cytotoxic T lymphocyte was found to be similar in mice immunized with Ab2 or irradiated tumor cells when examined at the precursor level. However, only 2F10 induces protective immunity against the growth of L1210/GZL tumor cells. The depletion of a L3T4+ T cell population from 2F10 immune mice was found to increase the effectiveness of transferred T cells to induce inhibition of tumor growth. The inability of 3A4 to induce antitumor immunity could be correlated with the presence of a population of Lyt2+ regulatory T cells. Collectively, these results demonstrate the existence of a regulatory network controlling the expression of effective tumor immunity. Our results demonstrate that selection of binding site-related Ab2 may not be a sufficient criteria for the development of an idiotype vaccine. A better understanding of the regulatory interactions induced by anti-idiotypes is needed for the design of effective antitumor immunotherapy.

Animals↗
PubMed1987

Development of selective IgM deficiency in systemic lupus erythematosus patients with disease of long duration.

Statistical analysis of serum immunoglobulin levels in 54 systemic lupus erythematosus (SLE) patients showed a decrease in serum IgM (normal 77 +/- 26 mg/dl; P less than 0.001) that was closely related to disease duration. The longer the duration of SLE, the more striking the decrease in serum levels of IgM (r = -0.74, P less than 0.01). Selective IgM deficiency (less than 47 mg/dl) occurred in SLE patients whose disease was clinically inactive or less active.

Adolescent↗
PubMed1987

Mechanical properties and ATPase activity in glycerinated cardiac muscle of hyperthyroid rabbit.

Isometric tension, tension transients in response to rapid step stretches in length and ATPase activity were measured at constant levels of various Ca2+ activations in glycerinated right ventricular papillary muscle of L-thyroxine-treated (14 daily injections of 0.2 mg/kg) and control rabbits. The isometric tension increased sigmoidally as Ca2+ was varied from slightly below pCa 7 to about pCa 6 both in thyroxine-treated and control preparations. The maximum isometric tension in thyroxine-treated preparations, however, was only about 66% of that in control. The tension transients were characterized by clear three distinct phases; the first phase of an immediate tension increase coincident with the stretch, the second phase of a rapid quasi-exponential tension decrease and the third phase of a delayed quasi-exponential tension rise. In thyroxine-treated preparations, relative to controls, the time for 63% tension reduction in the second phase decreased from 39.3 +/- 2.8 ms (mean +/- SD, n = 5) to 20.2 +/- 2.0 ms (p less than 0.001) and the time for 63% tension rise in the third phase decreased from 483.9 +/- 14.3 ms to 298 +/- 15.9 ms (p less than 0.001). The ATPase activity increased in a sigmoid fashion with increasing Ca2+ from slightly above pCa 7 to slightly below pCa 6 both in thyroxine-treated and control preparations. However, the tension cost (ATPase activity/tension) was about two times greater in the thyroxine-treated preparations than in controls.

Adenosine Triphosphatases↗
PubMed1987

ATPase activity and tension development in mechanically-skinned feline jaw muscle.

At a muscle length L0 (just taut), isometric tension and ATPase activity were measured at constant levels of various Ca2+ activations in muscle fibres (2-3 mm long and 34-66 microns in diameter) isolated from temporal, masseter and digastric (anterior belly) muscles. The isometric tension increased in a sigmoid fashion with increasing Ca2+ concentration from about pCa 6.60 to pCa 5.00 in the temporalis and from about pCa 6.37 to pCa 5.00 in both the masseter and digastric. The maximum isometric tension from four preparations of each muscle averaged 44.4 +/- 6.6 g/mm2 in the temporalis, 31.9 +/- 4.0 g/mm2 in the masseter, and 23.9 +/- 5.5 g/mm2 in the digastric. The ATPase activity also increased sigmoidally with increasing Ca2+ concentration from slightly below pCa 7.0 to pCa 5.0 in the temporalis, and from slightly above pCa 6.0 to pCa 5.0 in both the masseter and digastric. The maximum ATPase activity obtained from four preparations of each muscle averaged 0.35 +/- 0.06 mumol/mg protein per min in the temporalis, 0.29 +/- 0.06 mumol/mg protein per min in the masseter, and 0.18 +/- 0.04 mumol/mg protein per min in the digastric. The tension cost (ATPase activity/tension) estimated from these results was lower in the digastric than in the temporalis or masseter, indicating more economical ATP consumption in the digastric.

Adenosine Triphosphatases↗
PubMed1987

Transport and post-transport abnormalities of glucose metabolism in cardiocytes isolated from streptozotocin-induced diabetic rats.

The altered glucose utilization in cardiocytes isolated from streptozotocin (STZ)-induced diabetic rats and its reversibility to normal following 2-week insulin treatment were studied. 3-O-Methylglucose (3-O-MG) transport in cardiocytes isolated from normal rats was stimulated to 150% (P less than 0.01) above the basal level in the presence of 80 nM insulin. The basal 3-O-MG transport in diabetic rats was decreased to 41% of that in normal rats, and further an increase in 3-O-MG transport was not observed even in the presence of 80 nM insulin. Similar significant decreases in glucose uptake in the presence of both trace (0.8 microM) and 5.5 mM glucose were also found in diabetic rats. However, in normal rats, lactate release into the media was stimulated by only 16% (P less than 0.05), and glucose oxidation was not stimulated in the presence of insulin, there being no significant difference between normal and diabetic rats. On 2-week insulin treatment of diabetic rats, both the basal 3-O-MG transport and glucose uptake in the presence of trace and 5.5 mM glucose returned to normal levels, with significant improvement of the blunted acute insulin action. In addition, both lactate release and glucose oxidation were also significantly (P less than 0.05) increased by in vivo insulin treatment. The maximum insulin-stimulated 3-O-MG transport (r = -0.79, P less than 0.01) and glucose uptake in cells in the presence of 5.5 mM glucose (r = -0.74, P less than 0.01) both showed a negative correlation with the plasma glucose concentration, but not with the plasma free fatty acid level or the plasma triglyceride level.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗
PubMed1987

Effect of insulin on the glucose utilization in isolated cardiac myocytes from adult rat.

The acute effects of insulin on glucose utilization in isolated rat quiescent cardiac myocytes were studied. Insulin (80 nM) increased the rate of glucose clearance by 2-3 times in the presence of glucose ranging from 0.3 microM to 5.5 mM. Glucose transport, which was measured in terms of both D-glucose uptake in the presence of 0.3 microM D-glucose and initial rate of uptake of 3-O-methylglucose, was stimulated 3-fold in the presence of insulin. At higher glucose concentrations (greater than 100 microM), a decrease in glucose clearance rate due to a shift of the rate-limiting step from glucose transport to a post-transport step in the pathway of glucose metabolism was observed. At the physiological concentration of glucose (5.5 mM), about 73% of glucose was metabolized into lactate, about 10% was oxidized into CO2 and the rest (17%) remained inside the cells. The pentose phosphate pathway did not contribute to the glucose metabolism in these cells. Insulin (80 nM) significantly increased the uptake of glucose (112%), and the conversions of glucose into lactate (16%), glycogen (64%), and triglyceride (18%), but not into CO2 (3%). Insulin transiently increased the percentage of I-form of glycogen synthase by 16% above basal, but did not affect the percentage of a-form of glycogen phosphorylase. The content of glucose 6-phosphate in the cells was increased by 46% above the basal value in the presence of insulin. These results indicate that insulin has different acute stimulatory effects on various steps in the metabolic pathway of glucose in isolated quiescent cardiac myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Hyperproduction of polyhedrin-IGF II fusion protein in silkworm larvae infected with recombinant Bombyx mori nuclear polyhedrosis virus.

A gene coding for insulin-like growth factor II (IGF II) was constructed from 16 oligodeoxynucleotides synthesized chemically and cloned into EcoRI-SalI sites of pBR322. In this gene at ATG codon for methionine was introduced for cleavage by CNBr at the beginning of mature IGF II. For expressing foreign genes, a new host-vector system, with Bombyx mori silkworm larvae as the host and B. mori nuclear polyhedrosis virus (BmNPV) as the vector, has been developed. BmNPV genomic DNA codes polyhedrin which is a major protein of inclusion bodies and is mass-produced in infected silkworm larvae. We employed this polyhedrin production system to obtain a large yield of a foreign gene product. The coding region of the carboxy-terminal half of polyhedrin was removed and the remainder was ligated with the IGF II gene in phase to create a fusion protein gene consisting of the coding region of the amino-terminal half of polyhedrin and the IGF II gene. This fusion protein gene was combined in a plasmid with the promoter and 5' and 3' flanking regions of the polyhedrin gene. The resulting plasmid and the wild-type BmNPV genomic DNA were cotransfected into BM-N cells, and a recombinant virus was isolated by the limiting dilution method. The silkworm larvae infected with the recombinant virus produced 3.6 mg of the fusion protein per larva and the infected BM-N cells produced 0.3 mg per ml of culture. IGF II was released from the fusion protein produced by BM-N cells infected with the recombinant virus by CNBr treatment, purified by extraction with guanidine-HCl, column chromatography and HPLC and the correct amino-terminal amino acid sequence confirmed.

Animals↗
PubMed1987

Confluence of barosensory and nonbarosensory inputs at neurons in the ventrolateral medulla in rabbits.

In urethane-anesthetized rabbits, 209 spontaneously active neurons that responded to stimulation of aortic nerve A fibers were found within the ventrolateral medulla (VLM). The neurons, termed barosensory VLM neurons, were inhibited, except for three instances, by stimulation of A fibers. Forty-seven percent of barosensory VLM neurons tested (74 of 159) were activated antidromically by electrical stimulation of the dorsolateral funiculus at the C2 level. Activity of barosensory VLM neurons was enhanced by stimulation of carotid body chemoreceptors or the posterior hypothalamic area, whereas it was diminished by increases in arterial pressure elicited by injection of phenylephrine. Barosensory VLM neurons responded variously to stimulation, with two to three pulses at 40 or 100 Hz, of spinal afferents of cutaneous and muscle origins and the spinal trigeminal complex. Although stimulation of one group of somatosensory fibers could evoke different patterns of neuronal responses consisting of excitatory and inhibitory components, the following responses were most often encountered. Group II cutaneous afferents caused an inhibition. Recruitment of group III afferents brought about a brief excitatory component preceding it. Activation of group IV cutaneous fibers added a long latency excitatory component. Excitation of groups III and IV muscle afferents most often resulted in an inhibition, whereas stimulation of the spinal trigeminal complex elicited various combinations of excitatory and inhibitory components. These results are consistent with the view that neurons in the ventrolateral medulla receive barosensory and nonbarosensory inputs from various peripheral and central sources and participate in the control of sympathetic vasomotor activity and arterial pressure.

Afferent Pathways↗
PubMed1987

Electronmicroscopic study on biopsied rectal mucosa in adrenoleukodystrophy.

Rectal mucosal biopsies were performed for seven members of five families with adrenoleukodystrophy (ALD). Many histiocytes contained characteristic cytoplasmic lamellar inclusions that were identical to those seen in adrenocortical cells, brain macrophages, and Schwann cells of affected patients. The ultrastructural features were seen in all patients and also in two asymptomatic younger brothers who had presymptomatic ALD according to assay of very-long-chain fatty acids.

Adrenoleukodystrophy↗
PubMed1987

Common occurrence in Toyama of bronchial asthma induced by chironomid midges.

A total of 119 asthmatic children were investigated by prick tests for the hypersensitivity against chironomid antigens. The percentages of cases who showed positive prick tests to the antigens of the adults of Polypedilum kyotoense, Chironomus yoshimatsui and Tokunagayusurika akamusi, that of the larvae of Tokunagayusurika akamusi and of Dermatophagoides farinae were 23.5%, 17.6%, 7.6%, 16.0% and 94.2%, respectively. The correlations among the wheal size in prick test, the threshold dilution in the intradermal test, the RAST score, and the result of the provocation test were significant. The specific IgE antibodies against two additional midge species were measured with the Phadezyme RAST test in a total of 27 asthmatic cases who were positive to either of the 3 adult midge antigens previously tested. RAST was positive in 59.3% with Chironomus plumosus and 100% with Tanytarusus oyamai. In the RAST inhibition tests, the Polypedilum kyotoense antigen causing allergic reaction was shown to be quite independent from Dermatophagoides farinae. These results suggest that the extracts of chironomid midges have strong allergenicity, and are one of the important inhalant antigens causing asthma in Toyama.

Adolescent↗
PubMed1986

Tumor-specific idiotype vaccines. I. Generation and characterization of internal image tumor antigen.

The concept of idiotype vaccines against tumor-associated antigens (TAA) was tested in the DBA/2 L1210 lymphoma subline, L1210/GZL. Monoclonal antibodies against a TAA that cross-reacts with the envelope glycoprotein gp52 of the mammary tumor virus were used to make hybridoma anti-idiotype antibodies (Ab2). In this report we describe the characterization of monoclonal anti-idiotypic antibodies against the combining site of 11C1 (Ab1), which recognizes a shared determinant of gp52 of mouse mammary tumor virus (MMTV) and the TAA of L1210/GZL. Hybridomas expressing the internal image of gp52 were screened by an idiotype inhibition assay. Mice sensitized with radiated L1210/GZL cells produced specific delayed type hypersensitivity (DTH) against the Ab2 hybridoma. Five Ab2 hybridomas were selected and were used to immunize DBA/2 mice. Such immunized animals showed specific DTH reaction against a challenge with the L1210/GZL tumor cells. Similar results were obtained in mice immunized with purified Ab2. Fluorescence-activated cell sorter analysis demonstrated that fluorescence staining of L1210/GZL cells by 11C1 can be completely inhibited with preabsorption on Ab2 hybridoma cells. Mice immunized with 2F10 and 3A4 coupled to keyhole limpet hemocyanin (KLH) contained antibodies binding to MMTV. But only in mice immunized with 2F10-KLH was significant inhibition of L1210/GZL tumor growth observed. Collectively, these results indicate that certain anti-idiotypic antibodies can mimic the MMTV gp52 antigen, as well as the gp52-like epitope expressed on the L1210/GZL tumor cells. These properties of anti-idiotypic antibodies mimicking TAA could be exploited for making idiotype vaccines against tumors.

Animals↗