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T Hamaoka

Publications and source records attributed to T Hamaoka.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Clinical course of HIV-infected tuberculosis patients who admitted to the tuberculosis isolation ward: current problems of medical care].

To clarify the problems of medical care of HIV-infected tuberculosis patients, we investigated clinical course of six cases admitted to our tuberculosis isolation ward. All cases were sputum smear positive for tubercle bacilli at the time of diagnosis of tuberculosis. HIV-positive was confirmed at the same time or soon after the diagnosis of tuberculosis in four cases. CD4+ cell count was on the average 21/mm3 on admission, and all cases were defined as acquired immunodeficiency syndrome (AIDS) by the criteria of AIDS surveillance committee in Japan. Two patients presented with miliary tuberculosis and five documented evidence for intrathoracic and/or cervical lymph node involvement. All cases but one responded well to antituberculosis drugs, and sputum smears and cultures became negative soon after the initiation of therapy. However, the patients were still needed to be hospitalized for the treatment and control of complications other than tuberculosis after sputum negative conversion, and they stayed in the isolation rooms of our tuberculosis ward for 110 +/- 49 days. During the treatment for tuberculosis, each patient developed 3 to 8 complications of HIV infection such as pneumocystis carinii pneumonia (PCP) (four cases), bacterial infection (four cases), neuropathy (four cases), and HIV encephalopathy (three cases). The last two complication worsened active daily life. White blood cell count was more likely to fall when sulfamethoxazole/trimethoprim mixture for the prevention of PCP and antituberculosis drugs were administered together. In three cases, ST mixture could not be continued, then two patients developed PCP after changing to an alternative pentamidine inhalation. Although three patients discharged from our tuberculosis ward, four died of AIDS related complications other than tuberculosis, one died of tuberculosis (multidrug-resistant M. tuberculosis strain was not documented initially but was detected five months later), one died of tuberculosis meningitis after the discharge, and one was lost because he returned to his own country. The survival time between the start of treatment and death ranged from 90 to 244 days in five cases. Integrated medical care system both for HIV and tuberculosis is warranted for the management of HIV-infected tuberculosis patients since they suffer many complication in addition to tuberculosis. A guideline of methods and duration of isolation for tuberculosis is needed for the most effective care of HIV-infected tuberculosis patients in Japan.

AIDS-Related Opportunistic Infections↗
PubMed1997

The anti-tumor effects of IL-12 involve enhanced IFN-gamma production by anti-tumor T cells, their accumulation to tumor sites and in situ IFN-gamma production.

We investigated cellular and molecular mechanisms underlying the anti-tumor effects of IL-12. Intraperitoneal injections of rIL-12 into later stages of tumor-bearing mice induced not only a striking reversal of suppressed IFN-gamma-production by splenic T cells, but also complete regression of s.c. growing tumors. A massive infiltration of lymphoid cells was found following IL-12 treatment. Whereas fresh spleen cells obtained from IL-12-treated tumor-bearing mice failed to express IFN-gamma mRNA, significant levels of IFN-gamma mRNA were detected in the tumor mass of the same mice. The systemic administration of anti-IFN-gamma antibody (Ab) prior to IL-12 injection abrogated the anti-tumor effect of IL-12 although this Ab did neither inhibit accumulation of lymphoid cells to tumor sites nor in situ IFN-gamma expression. Importantly, while high levels of inducible nitric oxide synthase (iNOS) mRNA expression was induced in tumor masses after IL-12 treatment, its expression was completely inhibited by pretreatment with anti-IFN-gamma Ab. Thus, induction of tumor regression by IL-12 is ascribed to a series of events: a striking reversal of suppressed IFN-gamma production by anti-tumor T cells, their accumulation and IFN-gamma production at tumor sites, and manifestation of IFN-gamma activity as exemplified by iNOS expression.

Animals↗
PubMed1996

Identification of a novel transmembrane semaphorin expressed on lymphocytes.

Semaphorin (also known as collapsin) members are thought to be involved in axon guidance during neural network formation. Here, we report the isolation of a novel member, mouse semaphorin G (M-sema G), which encodes a semaphorin domain followed by a single putative immunoglobulin-like domain, a transmembrane domain, and a cytoplasmic domain. M-sema G is most closely related to M-sema F, which we previously reported, and semB and semC. These four members appear to constitute a transmembrane type subfamily in mouse semaphorins. In contrast to the predominant expression of M-sema F mRNAs in the nervous tissues, M-sema G mRNAs are strongly expressed in lymphoid tissues, especially in the thymus, as well as in the nervous tissues. The mRNAs are also detected in various cell lines from hematopoietic cells. By generating specific antibodies, we confirmed the strong expression of M-Sema G proteins on the surface of lymphocytes. These results provide the first evidence that semaphorin is expressed on lymphocytes and suggest that semaphorins may play an important role in the immune system, as well as in the nervous system.

Amino Acid Sequence↗
PubMed1996

A role for CD9 molecules in T cell activation.

Costimulation mediated by the CD28 molecule plays an important role in optimal activation of T cells. However, CD28-deficient mice can mount effective T cell-dependent immune responses, suggesting the existence of other costimulatory systems. In a search for other costimulatory molecules on T cells, we have developed a monoclonal antibody (mAb) that can costimulate T cells in the absence of antigen-presenting cells (APC). The molecule recognized by this mAb, 9D3, was found to be expressed on almost all mature T cells and to be a protein of approximately 24 kD molecular mass. By expression cloning, this molecule was identified as CD9, 9D3 (anti-CD9) synergized with suboptimal doses of anti-CD3 mAb in inducing proliferation by virgin T cells. Costimulation was induced by independent ligation of CD3 and CD9, suggesting that colocalization of these two molecules is not required for T cell activation. The costimulation by anti-CD9 was as potent as that by anti-CD28. Moreover, anti-CD9 costimulated in a CD28-independent way because anti-CD9 equally costimulated T cells from the CD28-deficient as well as wild-type mice. Thus, these results indicate that CD9 serves as a molecule on T cells that can deliver a potent CD28-independent costimulatory signal.

Animals↗
PubMed1996

Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a signal through thymic shared antigen-1/stem cell antigen-2.

During T cell development in the thymus, the expression of thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2), a glycosylphosphatidylinositol (GPI)-anchored differentiation antigen, is developmentally regulated. The expression level of TSA-1 is the highest in most immature CD4- CD8- thymocytes, high in CD4+ CD8+ thymocytes, but barely detectable in mature CD4+ CD8- or CD4- CD8- thymocytes and peripheral T cells. We have previously shown that surface TSA-1 expression in peripheral T cells is induced upon activation and that anti-TSA-1 mAb inhibits the T cell receptor (TCR) signaling pathway in activated T cells. In the present study, we have analyzed a role of TSA-1 in thymic selection events, especially in TCR-mediated apoptosis. In in vitro experiments, anti-TSA-1 blocked anti-CD3-induced cell death of T cell hybridomas. When anti-TSA-1 was injected into newborn mice in vivo together with anti-CD3 epsilon or anti-TCR-beta, TCR/CD3-mediated apoptosis of thymocytes was almost completely blocked. The blockade of apoptosis was defined by the inhibition of, first, the decrease in total number of thymocytes; second, the decrease in percentages of CD4+ CD8+ thymocytes; and third, the induction of DNA fragmentation. However, anti-TSA-1 did not block either steroid- or radiation-induced apoptosis, indicating that a signal via TSA-1 does not inhibit a common pathway of thymocyte apoptosis. Since TCR-mediated apoptosis is pivotal in thymic ontogeny, these results suggest that TSA-1/Sca-2 is an important cell surface molecule regulating the fate of a developing T cell.

Animals↗
PubMed1996

IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones.

We investigated the role of IL-12 in proliferation of various Th cell clones (class II-alloreactive (4-86 and 4-55) and keyhole limpet hemocyanin + self I-Ek-reactive (9-16)) following stimulation with Ag on APCs. These clones proliferated in response to stimulation with rIL-2, rIL-12, or Ag/APC. The proliferation induced by Ag/APC stimulation was not affected by anti-IL-2 Ab but was markedly inhibited by anti-IL-12 Abs. Consistent with this finding was the absence of detectable IL-2 activity in culture supernatants 12 to 48 h after Ag/APC stimulation, and the detection of significant levels of IL-12 in an Ab-capture bioassay. IL-12 was produced within 12 h after Ag/APC stimulation, reaching a peak after 18 to 24 h. The production of IL-12 in cultures of Th clones and APC contrasted with the production of IL-2 but not IL-12 upon allostimulation of primary T cells and the inhibition of their proliferation exclusively by anti-IL-2 Abs. Analysis of the expression of IL-12-binding sites on Th cells revealed low levels of IL-12 receptors in resting Th clones but high IL-12R levels 2 to 3 days after Ag/APC stimulation, declining gradually thereafter. The changes in IL-12R expression levels correlated closely with the IL-12 responsiveness of Th populations at various times after Ag/APC stimulation; Th populations obtained 3 and 10 days after Ag/APC stimulation exhibited very high and weak or marginal responsiveness to rIL-12, respectively, whereas the responses to rIL-2 were comparable in both Th populations. These results indicate that the Ag/APC-stimulated proliferation of terminally differentiated Th clones, in contrast to naive T cells, depends on the production of IL-12 by APC and on the simultaneous up-regulation of IL-12R on Th cells rather than on an IL-2 autocrine mechanism.

Animals↗
PubMed1996

Antitumor and antimetastatic effects of interleukin 12.

Interleukin 12 (IL-12) has a pivotal role in controlling cell-mediated immunity through a number of important biological activities, such as secretion of interferon-gamma (IFN-gamma). In this review, we report our recent results regarding the antitumor and antimetastatic effects of IL-12. Five intraperitoneal injections of recombinant IL-12 (rIL-12) into mice bearing subcutaneous tumors (CSA1M fibrosarcoma) induced complete tumor regression, irrespective of whether tumors were at early or late stages of growth. Furthermore, IL-12-treated mice that had rejected the primary tumor exhibited complete resistance to rechallenge with the same tumor but did not reject a second syngeneic tumor. Immunohistochemical analyses following IL-12 treatment revealed that CD4+ and CD8+ T-cells had infiltrated the tumor. More importantly, IFN-gamma mRNA expression was observed in fresh tumor masses from tumor-bearing mice receiving IL-12 treatment. The importance of IFN-gamma was further demonstrated by the observation that systemic administration of anti-IFN-gamma monoclonal antibody prior to IL-12 treatment completely abrogated the antitumor effect of IL-12. We next investigated the ability of rIL-12 to modulate the outgrowth of metastatic tumor cells in an ovarian carcinoma (OV-HM) model. This aggressive tumor showed rapid growth of the primary tumor mass, a high incidence of metastases to the lung and lymph nodes, and invasion from the primary subcutaneous site into the peritoneal cavity. At approximately 1 month after tumor implantation, primary tumors in animals without palpable lymph nodes were surgically resected. When examined 2 months later, most animals had developed lymph node and lung metastases. In contrast, rIL-12 injections following tumor resection inhibited the development of metastases in both the lung and lymph nodes. Even in mice showing signs of lymph node metastases or invasion of the abdominal wall before primary tumor resection, rIL-12 administration following tumor resection prevented further invasion into the peritoneal cavity and metastatic tumor cell growth in the lung. Our results demonstrate that administration of rIL-12 to tumor-bearing mice results in tumor regression through mechanisms involving efficient IFN-gamma production by antitumor T-cells at tumor sites in situ and the establishment of a tumor-specific protective immune response. The results also indicate that IL-12 can induce a curative immune response in the face of an aggressive micrometastasizing tumor.

Animals↗
PubMed1996

CD28 co-stimulatory signals induce IL-2 receptor expression on antigen-stimulated virgin T cells by an IL-2-independent mechanism.

Intravenous sensitization of C57BL/6 (B6) mice with class II H-2-disparate B6-C-H-2bm12(bm12) resting B cells induced anti-bm12 CD4+ T cell tolerance as shown by hyporesponsiveness in the anti-bm12 mixed lymphocyte reaction (MLR). The present study investigated the mechanism(s) of the failure of bm12 B cells to stimulate the proliferation of B6 anti-bm12 CD4+ T cells. While stimulation in vitro to B6 splenic T cells with bm12 antigen-presenting cells (APC) induced IL-2 mRNA expression and IL-2 production, T cells stimulated with bm12 B cells expressed much less IL-2 mRNA and secreted very low but detectable levels of IL-2. Moreover, the T cells stimulated with the bm12 B cells did not proliferate and this was not corrected by the addition of rIL-2 responsiveness. Further, whereas IL-2 receptor (IL-2R) alpha chain expression was significantly induced on B6 T cells stimulated with bm12 APC; stimulation with bm12 B cells did not induce IL-2R expression over background levels. However, virgin T cells stimulated with both bm12 B cells and anti-CD28 mAb proliferated and displayed a dramatic increase in IL-2 production as well as IL-2R expression to levels commensurate with those resulting from bm12 B cells plus anti-CD28 mAb even in the presence of sufficient amounts of anti-IL-2 mAb for neutralizing produced IL-2; while levels of IL-2R were significantly lower compared to those induced in the absence of anti-IL-2 mAb, increased frequencies of IL-2R+ cells were comparable. Conversely, IL-2R was not induced by bm12 B cell stimulation in the presence of IL-2. Moreover, IL-2R expression and proliferation induced by stimulation with bm12 APC was inhibited by CTLA-4-Ig, a soluble recombinant fusion protein capable of blocking the CD28 co-stimulatory signals not only stimulate IL-2 production but also induce IL-2R expression by an IL-2-independent mechanism.

Abatacept↗
PubMed1996

Molecular mechanisms underlying IFN-gamma-mediated tumor growth inhibition induced during tumor immunotherapy with rIL-12.

The present study investigates the molecular mechanisms by which IFN-gamma produced as a result of in vivo IL-12 administration exerts its anti-tumor effects. rIL-12 was administered three or five times into mice bearing CSA1M fibrosarcoma, OV-HM ovarian carcinoma or MCH-1-A1 fibrosarcoma. This regimen induced complete regression of CSA1M and OV-HM tumors but only transient growth inhibition of MCH-1-A1 tumors. The anti-tumor effects of IL-12 were associated with enhanced induction of IFN-gamma because these effects were abrogated by pretreatment of hosts with anti-IFN-gamma antibody. Exposure in vitro of the three types of tumor cells to rRFN-gamma resulted in moderate to potent inhibition of tumor cell growth. IFN-gamma stimulated the expression of mRNAs for an inducible type of NO synthase (iNOS) in CSA1M cells and indoleamine 2,3-dioxygenase (IDO), an enzyme capable of degrading tryptophan, in OH-HM cells, but induced only marginal levels of these mRNAs in MCH-1-A1 cells. In association with iNOS gene expression, IFN-gamma-stimulated CSA1M cells produced a large amount of NO which functioned to inhibit their own growth in vitro. Although OV-HM and MCH-1A1 cells did not produce NO, they also exhibited NO susceptibility. Whereas the tumor masses from IL-12-treated CSA1M-bearing or OV-HM-bearing mice induced higher levels of iNOS (for CSA1M) or IDO and iNOS (for OV-HM) mRNAs, the MCH-1-A1 tumor mass expressed lower levels of iNOS mRNA alone. Moreover, massive infiltration of CD4(+) and CD8(+) T cells and Mac-1(+) cells was seen only in the CSA1M and OV-HM tumors. Thus, these results indicate that IFN-gamma produced after IL-12 treatment induces the expression of various genes with potential to modulate tumor cell growth by acting directly on tumor cells or stimulating tumor-infiltrating lymphoid cells and that the effectiveness of IL-12 therapy is associated with the operation of these mechanisms.

Animals↗
PubMed1996

Inhibition of growth and metastasis of ovarian carcinoma by administering a drug capable of interfering with vascular endothelial growth factor activity.

The present study investigates the relationship between in vivo growth/metastasis of tumor cells and their capacity to produce the vascular endothelial growth factor (VEGF), as well as the regulation of tumor growth/metastasis using an angiogenesis-inhibitory drug. Two cloned tumor cell lines designated OV-LM and OV-HM were isolated from a murine ovarian carcinoma OV2944. OV-LM and OV-HM cells grew in cultures at comparable rates. However, when transplanted s.c. into syngeneic mice, OV-HM exhibited a faster growth rate and a much higher incidence of metastasis to lymph nodes and lung. Histologically, intense neovascularization was detected in sections of OV-HM but not of OV-LM tumor. OV-HM and OV-LM tumor cells obtained from in vitro cultures expressed high and low levels of VEGF mRNA, respectively. A difference in VEGF mRNA expression was much more clearly observed between RNAs prepared from fresh OV-HM and OV-LM tumor masses: RNA from OV-HM contained larger amounts of VEGF mRNA, whereas RNA from OV-LM exhibited only marginal levels of VEGF mRNA. An angiogenesis-inhibitory drug, FR118487 inhibited the VEGF-mediated in vitro growth of endothelial cells but did not affect the expression in vitro of VEGF mRNA by OV-HM tumor cells. Intraperitoneal injections of FR118487 into mice bearing OV-HM tumors resulted in: (i) a subsequent growth inhibition of primary tumors; (ii) a marked decrease in neovascularization inside tumor masses expressing comparable levels of VEGF mRNA to those detected in control OV-HM masses; and (iii) almost complete inhibition of metastasis to lymph nodes and lung. These results indicate that growth/metastasis of tumor cells correlates with their VEGF-producing capacity and that an angiogenesis inhibitor, FR118487, inhibits tumor growth and metastasis through mechanism(s) including the suppression of VEGF function in vivo.

Animals↗
PubMed1996

Evidence of direct recognition subset in xeno-reactive helper T cells.

There are two functional subsets of alloreactive helper T cells: one recognizes the alloantigens on self-antigen-presenting cells (APCs), and the other recognizes the alloantigens on allo-APCs. In this study, we analyzed which specific Th cells have a possible effect on concordant-xenograft rejection responses and how Th cells recognize xeno-antigens. In the proliferative response stimulated with spleen cells obtained from rats (r-SPC), mouse T cells (m-Tc) were not inhibited by GK1.5 (CD4) or 2.43 (CD8) antibodies. In a xeno-mixed lymphocyte reaction, m-Tc that included APC (APC(+)) proliferated when stimulated with r-SPC APC(+) or APC(-). In contrast, B6 T cell APC(-) proliferated only when stimulated with r-APC(+)SPC but not when stimulated with APC(-). The m-Tc lines responded to F344 SPC APC(+) but not to SPC APC(-); however, the m-Tc line did not respond to SPC from another rat strain. We hypothesize that both CD4+ Th and CD8+ Th are included in the concordant xeno-reactive Th; there are both xeno-APC-restricted Th and self-APC-restricted Th; and xeno-APC-restricted Th recognizes xeno-major histocompatibility complexes.

Animals↗
PubMed1996

Noninvasive measures of oxidative metabolism on working human muscles by near-infrared spectroscopy.

The purpose of this study was to determine whether the initial rate of hemoglobin and myoglobin deoxygenation during immediate postexercise ischemia, a reflection of muscle O2 consumption (VO2mus), can be a quantitative measure of muscle oxidative metabolism. The finger flexor muscles of five healthy men (aged 25-31 yr) were monitored by 31P-magnetic resonance spectroscopy for changes in phosphocreatine (PCr), Pi, and pH. Tests were conducted during 15 min of cuff ischemia and during 5 min of submaximal isotonic grip exercise at 10, 20, 30, and 40% of maximal voluntary contraction, one contraction every 4 s. The VO2mus changes were also monitored by near-infrared spectroscopy with continuous wave. The VO2mus during exercise was expressed relative to the resting value. The resting metabolic rate, calculated from the PCr breakdown rate after complete O2 depletion, was 0.0010 (SD) mM ATP/s. During submaximal exercise (pH > 6.9), the VO2mus increased with a rise in intensity (0.036 +/- 0.011, 0.054 +/- 0.016, 0.062 +/- 0.012, and 0.067 +/- 0.020 mM ATP/s during 10, 20, 30, and 40% maximal voluntary contraction, respectively) and showed significant correlation with changes in both calculated ADP and PCr values (r2 = 0.98 and r2 = 0.99, respectively). In conclusion, because of the significant correlation with regulatory metabolites (ADP and PCr) of oxidative phosphorylation, O2 decline rate in immediate postexercise ischemia determined by near-infrared spectroscopy with continuous wave can be utilized for the quantitative evaluation of localized muscle oxidative metabolism.

Adult↗
PubMed1995

Modulation of TCR-mediated signaling pathway by thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2).

Thymic shared antigen-1 (TSA-1) is a glycosyl-phosphatidylinositol (GPI)-anchored differentiation Ag expressed on murine lymphocytes, and is identical to stem cell Ag-2 (Sca-2). Using newly established mAb against TSA-1/Sca-2, we have previously shown that surface TSA-1 expression is induced upon activation in T cells, and that anti-TSA-1 inhibits IL-2 production induced by anti-CD3 stimulation in T cell hybridomas. In the present study, we have analyzed the functional role of TSA-1 during T cell activation using normal T cells, T cell hybridomas, and transfected Jurkat cell lines that expressed either GPI-anchored or transmembrane form of TSA-1. Anti-TSA-1 inhibited IL-2 production from normal T cells stimulated with soluble anti-CD3 plus accessory cells. Anti-TSA-1 exhibited the inhibitory effect on T cells, but not on accessory cells, because anti-TSA-1 inhibited IL-2 production in Jurkat cells transfected with TSA-1 cDNA, but not in control transfectant. A transmembrane form of TSA-1 was expressed in Jurkat cells by fusing the extracellular portion of TSA-1 to the transmembrane and cytoplasmic regions of the class 1 Db. The analysis using this transfectant revealed that anti-TSA-1-mediated inhibition of IL-2 production did not require the GPI anchor of TSA-1. Finally, in addition to the inhibition of IL-2 production, tyrosine phosphorylation of CD3 zeta-chains observed following TCR stimulation, one of the important early activation events, was markedly reduced by anti-TSA-1. These results imply that TSA-1/Sca-2 plays an important regulatory role in the TCR signaling pathway of activated T cells in addition to its role in T cell differentiation.

Animals↗
PubMed1995

Administration of recombinant interleukin 12 prevents outgrowth of tumor cells metastasizing spontaneously to lung and lymph nodes.

The present study investigates the ability of recombinant interleukin 12 (rIL-12) to modulate the growth of a primary tumor as well as the outgrowth of metastatic tumor cells in an ovarian carcinoma (OV-HM) model. This aggressive tumor displayed rapid growth of the primary tumor mass, high incidence of metastases to lung and lymph nodes, and invasion from the primary s.c. site to the peritoneal cavity. Starting 12 days after s.c. tumor cell implantation, several i.p. injections of rIL-12 at 2-3 day intervals resulted in regression of growing tumors. These treated mice did not show signs of metastases or tumor recurrence at the original site. One month after tumor implantation, untreated mice did not have visible lung metastasis, but some did have palpable lymph nodes. At this stage, the primary tumors of animals without palpable lymph nodes were surgically resected. When examined 2 months later, most animals had developed lymph node and lung metastases. In contrast, rIL-12 injections after tumor resection inhibited the development of metastases in both lung and lymph nodes. This contrasted with the failure of IL-2 to prevent metastases. Even for mice already showing signs of lymph node metastases or invasion of the abdominal wall, rIL-12 administration after tumor resection prevented further invasion to the peritoneal cavity and growth of metastatic tumor cells in lung. It was somewhat surprising that the IL-12 treatment of animals after 1 month of tumor growth without resection also resulted in complete tumor regression, as well as eradication of micrometastasis that would have occurred before the treatment. Moreover, they exhibited resistance to a rechallenge with the same tumor but not with a second tumor. Thus, this tumor system provides a relevant model to clinical situations in terms of treatment of advanced tumors and metastases. These results also indicate that IL-12 can induce a curative immune response, even in the face of an aggressive micrometastasizing tumor.

Animals↗
PubMed1995

cDNA cloning and characterization of a novel receptor-type protein tyrosine phosphatase expressed predominantly in the brain.

Protein tyrosine phosphatase has the potential to control various cellular events by negatively regulating the extent of tyrosine phosphorylation. Here, we report the isolation of a murine receptor protein tyrosine phosphatase, PTPBR7, which is expressed almost exclusively in the brain. Though the cytoplasmic portion of PTPBR7 reveals high similarity to HePTP/LC-PTP and STEP, these are, unlike PTPBR7, non-receptor protein tyrosine phosphatases. Unlike most receptor protein tyrosine phosphatases, PTPBR7 has only one cytoplasmic phosphatase domain, and its extracellular domain reveals no obvious structural similarity to known molecules. Thus, PTPBR7 defines a new subfamily of receptor-type protein tyrosine phosphatases. The putative extracellular domain of PTPBR7 was expressed in COS-7 cells as a chimeric fusion protein with an immunoglobulin Fc portion (PTPBR7-Fc). PTPBR7-Fc was secreted in the culture supernatant, confirming the capability of the extracellular domain of PTPBR7 to translocate across the cytoplasmic membrane. The cytoplasmic portion of PTPBR7 was expressed as a fusion protein in bacteria and was demonstrated to have catalytic activity. The expression of PTPBR7 was detectable in brain and especially in cerebellum but undetectable in liver, lung, heart, kidney, thymus, bone marrow, and spleen. In situ hybridization analysis revealed the most prominent signal in Purkinje cells. The predominant expression of PTPBR7 in the brain suggests that PTPBR7 may have role(s) in neuronal cells.

Amino Acid Sequence↗
PubMed1995

Regulatory mechanisms of antitumor T cell responses in the tumor-bearing state.

Tumor-bearing hosts develop antitumor immune responses. However, a number of immunosuppressive mechanisms come into operation with the progression of tumor growth. This article will review the observations regarding the modulation of antitumor immune responses in the tumor-bearing state, and consider the mechanisms underlying tumor-induced immune defects, especially in the light of the induction of an abnormal cytokine network. We will also describe the restoration of suppressed antitumor immune responses by administration of a particular cytokine, interleukin-12.

Animals↗