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K Hojo

Publications and source records attributed to K Hojo.

At least 55 records · Page 3Linked to original sources

Pattern of recurrence after hepatic resection for colorectal metastases.

Between 1978 and 1989, 159 patients with liver metastases from colorectal cancer underwent hepatic resection. Of 134 patients in whom metastases were confined to the liver, 109 had tumours removed completely with histologically negative resection margins. Two patients died in hospital. Ultrasonographically guided partial resection was performed in 80 patients, lateral segmentectomy in seven and lobectomy in 22. The 5-year survival rate of patients undergoing potentially curative resection was 47.9 per cent. Patients with metachronous tumours showed a significantly better prognosis than those with synchronous lesions in both univariate (P < 0.01) and multivariate (P = 0.01) analysis. During a median follow-up of 35.4 months, 64 patients developed recurrence, including 34 in the liver, 20 in the lung and 12 in the abdominal cavity. Of those with hepatic recurrence, ten patients developed tumours at the initial resection bed, seven in the same lobe, five in the contralateral lobe and 12 in both lobes. Ultrasonographically guided partial liver resection did not increase the risk of hepatic recurrence.

Adult↗

A 60-kDa thymic epithelial cell surface protein as a potent molecule mediating the cellular interaction with immature T cells.

A unique 60-kDa surface protein expressed on the thymic epithelial cells was characterized as a potent molecule participating in the interaction between thymic stromal cells (TSC) and immature T cells. Previously, we reported an athymic mouse-derived T cell clone, N-9F, which proliferates on TSC. In the present study, we established a TSC clone, SL10.3, from a BALB/c mouse. SL10.3 has an epithelial cell nature and supports N-9F and fetal thymocytes growth in vitro. The two rat monoclonal antibodies, AS19 and AS32, directed to the SL10.3 cell surface inhibited N-9F and fetal thymocytes growth on SL10.3, suggesting that the reactive molecule may mediate the cellular interaction between TSC and immature T cells. Both antibodies are directed to the same 60-kDa protein with a pI point of 5.4, but to different epitopes on the protein. The 60-kDa protein is distributed on thymic epithelial cells, fibroblasts, and vascular endothelial cells, but not on the hematopoietic cells tested.

Animals↗

Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. I. Comparison of pathology, delayed type hypersensitivity, and antibody.

In the present study, it was demonstrated that there were marked strain differences in susceptibility to the induction of our new murine model of experimental autoimmune orchitis (EAO; definite orchitis with hypospermatogenesis) induced by two or three sc injections with viable syngeneic testicular germ cells (TC) without any adjuvants. Among 12 inbred strains of mice examined, the A/J (H-2a), C3H/He (H-2k), and C3H/HeN (H-2k) strains were highly susceptible, whereas the C57BL/6N (H-2b), C57BL/10Sn (H-2b), BALB/cAnN (H-2d), AKR/N (H-2k), CBA/JN (H-2k), C3H/HeJ (H-2k), and MRL/lpr (H-2k) strains were low susceptible, and the DBA/2N (H-2d) as well as C3H/BiKi (H-2k) strains were resistant. In particular, mice of the H-2k haplotype demonstrated varying degrees of susceptibility, from highly to totally resistant, to the induction of EAO. Disease susceptibility to this type of EAO does not seem to be associated with a particular H-2 haplotype. All mice of the highly susceptible strains that received two injections of TC (TC x 2) developed a significant increase in both levels of delayed footpad reaction (DFR) to TC and anti-TC antibodies measured by ELISA. In the low susceptible and the resistant strains receiving TC x 2 or TC x 3, there was no correlation between the immune responses and the susceptibility to disease in these strains, with the exception of the BALB/cAnN mice receiving TC x 3. The low susceptible and the resistant mice that received TC x 2 were classified into four groups based on the DFR and antibody response: the C57BL/6N, BALB/cAnN, CBA/JN, and C3H/HeJ strains were both positive, and the C57BL/10Sn and AKR/N strains were both negative or very low; the DBA/2N and MRL/lpr strains showed negative DFR and positive antibody response, and the C3H/BiKi strain showed quite the opposite. Almost all mice of the 12 inbred strains that received TC x 3 showed positive antibody response, although its level varied. There seems to be no linkage between the cell-mediated and humoral immune responses and the H-2 locus in our new EAO model.

Animals↗

Genetic susceptibility to the induction of murine experimental autoimmune orchitis (EAO) without adjuvant. II. Analysis on susceptibility to EAO induction using F1 hybrid mice and adoptive transfer system.

In our novel murine model of experimental autoimmune orchitis (EAO) induced by two or three injections of viable syngeneic testicular germ cells (TC) alone, significant differences in susceptibility to the induction of EAO were found, and the disease susceptibility did not seem to be associated with a particular H-2 haplotype. The H-2 identical background disparate (highly susceptible x low susceptible)F1 hybrids, (C3H/He x C3H/HeJ)F1 and (C3H/HeJ x C3H/He)F1 mice, were highly susceptible to the induction of EAO. The H-2 identical background disparate (highly susceptible x resistant)F1 hybrids, (C3H/He x C3H/BiKi)F1 and (C3H/BiKi x C3H/He)F1 mice, were low susceptible to the induction of EAO. Both the H-2 and background disparate (highly susceptible x resistant)F1 hybrids, (C3H/He x DBA/2N)F1 and (DBA/2N x C3H/He)F1 mice, were equally resistant to EAO induction. In the susceptible hybrids, both delayed footpad reaction (DFR) and antibody responses to TC increased. On the other hand, in the resistant hybrids, the levels of anti-TC antibodies were elevated but the DFR to TC remains depressed. This suggests that the antibody production and induction of DFR may be under different genetic controls and that cellular immunity plays an important role in this EAO induction. In order to search for the mechanistic basis for low susceptible C3H/HeJ and resistant C3H/BiKi mice, these mice received orchitis-inducible spleen cells (SPCs) from C3H/He mice. C3H/HeJ mice were highly susceptible to passive EAO. In contrast, disease-resistant C3H/BiKi mice failed to develop passive EAO. In addition, we examined whether or not regulatory cells capable of preventing the disease induction were generated in low susceptible C3H/HeJ and resistant C3H/BiKi mice immunized with TC. Transfer of SPCs from TC-immunized C3H/HeJ and C3H/BiKi mice into C3H/He mice before the EAO challenge had no suppressive effect on subsequent disease induction.

Animals↗

Murine experimental autoimmune orchitis (EAO) induced by syngeneic testicular germ cells (TC) alone: orchitogenic and lymphostimulatory activities of TC from mice at various ages.

As part of our continuous investigations on the immune pathogenesis of a new experimental autoimmune orchitis (EAO) model without the use of adjuvant in C3H/He mice, the developmental patterns of autoantigenicity of viable syngeneic testicular germ cells (TC) during the postnatal period were investigated by examining the orchitogenic and immunogenic activities of TC, the lymphostimulatory activities of TC (the cytokine release from sensitized spleen cells (SPC) in response to TC), and the immunohistochemical localization of autoantigens in the testes of normal mice at various weeks of age. TC from 6-week-old mice had the capability of inducing EAO (orchitogenicity) for the first time. Delayed-type hypersensitivity-inducing capacity and anti-TC antibody-eliciting capacity were initially observed in mice immunized with TC from 4-week-old mice. A significant stimulation of interleukin 5 (IL-5) and interleukin 6 (IL-6) production by sensitized SPC was detectable when the TC from 3-week or older mice were employed as a stimulant. Interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) production was detected with TC from 4-week or older mice. Immunohistochemical staining reaction with anti-TC antisera was primarily localized at the acrosomal portion of spermatids and spermatozoa in the seminiferous tubules and was detected in early and late spermatids of mice as early as 3 weeks. Thus, from these chronological data it is suggested that the appearance of the lymphostimulatory activities of TC consistently precedes that of the orchitogenic activity and that the production of IL-5 and IL-6 (Th 2 cytokine) by sensitized SPC upon in vitro TC stimulation is detectable earlier than the production of IL-2 and IFN-gamma (Th 1 cytokine) in the postnatal period.

Aging↗

Inhibition of a novel model of murine experimental autoimmune orchitis by intravenous administration with a soluble testicular antigen: participation of CD8+ regulatory T cells.

Recently, we established a novel murine model of experimental autoimmune orchitis (EAO) in C3H/He mice by means of two sc injections of 1 x 10(7) viable syngeneic testicular germ cells (TC) without the use of any adjuvants. Using this model, an effective and reproducible system of immunoregulation in EAO was developed. The induction of this EAO was suppressed by pretreatment with five iv injections of a soluble (deaggregated) form of murine testicular antigen (mTA). The antigen, mTA, was prepared by acid extraction and ammonium sulfate precipitation of defatted testes and epididymides. The development of EAO and relevant delayed-type hypersensitivity was suppressed in an antigen-specific fashion, but anti-TC antibody formation was not affected. A single dose of cyclophosphamide at 2 days after the tolerogenic regime abrogated the unresponsiveness to EAO. Three doses of recombinant interleukin 2 at every other day starting on the next day of the last pretreatment did not overcome the unresponsiveness to EAO. CD8+ T cells isolated from the spleen of deaggregated mTA-pretreated animals could adoptively transfer suppression against EAO into naive recipients, whereas CD4+ T cells failed to transfer the suppression.

Animals↗

Suppression of efferent limb of testicular autoimmune response by a regulatory CD4+ T cell line in mice.

A murine T cell line (designated as C.Ts) as a mediator of suppression of experimental autoimmune orchitis (EAO) was established. The method of establishment of C.Ts cell line was preparing spleen cells from C3H/He mice hyperimmunized with testicular germ cells (TC) and the repeated selection of the lymphocytes in vitro by stimulation with mouse testicular antigens (mTA). The C.Ts cells were Thy1.2+, surface immunoglobulin-, CD3+, CD4+ and CD8-. The cells could suppress the induction of EAO when transferred into actively EAO-sensitized mice only at the pre-clinical stage of the disease (efferent limb of the autoimmune response). The transferred C.Ts cells significantly inhibited both cellular and humoral immune responses to TC in the recipients in an antigen-specific manner. The disease suppression by C.Ts cells was found to depend upon their cell number, and their suppressive activity was markedly augmented by in vitro stimulation with mTA.

Animals↗

[A case of adenocarcinoma of lung cancer with multiple brain metastasis and lymphangitis carcinomatosa responding well to chemotherapy with carboplatin, etoposide and ifosfamide].

A 75-year-old male who suffered from adenocarcinoma of lung cancer with multiple brain metastases, developed left hemiplegia. After diagnosis, he was treated with 4,000 cGy whole brain radiation, but soon after advanced lymphangitis carcinomatosa set in and his general condition deteriorated. He was administered carboplatin combination with etoposide and ifosfamide. Lymphangitis carcinomatosa disappeared, and the main tumor of lung and brain metastases were not growing. We recommended carboplatin for an old patient or one in poor condition, because it had less cytotoxicity and retained the same antitumor activity compared with cisplatin.

Adenocarcinoma↗

Establishment of an experimental model of autoimmune epididymo-orchitis induced by the transfer of a T-cell line in mice.

A murine T-cell line derived from BALB/c mice (designated B.T.1) was established which was capable of adoptively transferring experimental autoimmune orchitis (EAO) in normal recipients. The protocol consisted of preparing lymphocytes obtained from the mice that were immunized with syngenetic testicular germ cells (TGC) and the subsequent repeated selection of the lymphocytes in vitro by stimulation with murine testicular antigens (mTA). Phenotypic analysis revealed that B.T.1 cells were CD4+ T-cells. Intra-peritoneal inoculation of as few as 1 x 10(5) B.T.1 cells, that were stimulated in vitro with mTA before the inoculation, was capable of transferring EAO to naive recipients. In the latter, both delayed type hypersensitivity (DTH) and humoral responses to TGC were augmented. The transferred lesion was characterized by infiltration of inflammatory cells into the epididymis and rete testis and widespread aspermatogenesis in the testis. The transfer of EAO was unsuccessful when the recipients received B.T.1 cells that were maintained in culture medium without stimulation with mTA. In these recipients, anti-TC DTH was not detected, although the specific humoral response was observed. In-vitro characterization of the biological activity of B.T.1 cells revealed that the line had no cytolytic activity against TGC but the culture supernatant had macrophage migration inhibitory activity involved in the DTH response. Therefore, the DTH responsiveness transferred by B.T.1 cells was found to correlate with their orchitis-inducing capacity.

Animals↗

[Comparison of surgical therapy and combined irradiation in rectal cancer--second report. Effect of irradiation and ACNU on the tumor].

As part of a joint study on preoperative radiotherapy for developing an optimal mode of rectal cancer therapy, ACNU sensitization was studied in a total of 120 cases, with the cooperation of 48 facilities participating nationwide. The following results were obtained. Improvement in depth of invasion was more distinct in the combination preoperative therapy-ACNU group than in the preoperative radiotherapy group, with no other significant differences between the two. This finding suggests that dose and administration method could be improved. White blood cells and platelets were reduced in some cases of the ACNU combination group, but these reductions were not serious enough to impede surgical procedures. In addition, no significant difference in complications was noted between the two.

Adenocarcinoma↗

Preservation of urine voiding and sexual function after rectal cancer surgery.

In order to decrease the urinary and sexual morbidity which follows radical pelvic lymphadenectomy for rectal cancer, we began selective preservation of the pelvic autonomic nerves. Between 1985 and 1987, 134 patients with rectal cancer underwent a curative resection (52 abdominoperineal resections, 82 sphincter-saving resections) with extended pelvic lymphadenectomy and selective pelvic autonomic nerve preservation (PANP). PANP was classified into five degrees depending on the extent of pelvic dissection. First-degree PANP indicates complete preservation of the nerves; second-degree PANP indicates destruction of the hypogastric plexus: third-degree PANP indicates partial preservation of the pelvic autonomic plexus; fourth-degree PANP indicates bilateral or unilateral preservation of only the fourth pelvic parasympathetic nerve; and fifth-degree PANP indicates complete destruction of the pelvic autonomic nerves. Most patients with first-degree PANP were able to spontaneously void 7-10 days following the operation. However, 78 percent (28/36) of patients with fifth-degree PANP had not regained bladder sensation by the third postoperative week and were discharged with an indwelling catheter; 58 percent (21/36) had not regained bladder sensation by the 60th postoperative day. The cystometric data indicate a progressive decline in bladder sensation and function with increasingly extensive pelvic dissection. However, preservation of only the fourth parasympathetic nerve (fourth-degree PANP) resulted in partial sparing of bladder sensation and voiding function. Evaluation of sexual function in males under 60 years of age revealed that only 31 percent (12/39) recovered erectile function and only 19 percent (6/39) recovered normal ejaculatory function in the first postoperative year. Most of these patients had complete preservation of their pelvic autonomic plexus (i.e., first-degree PANP). Four patients with partial PANP have recovered erectile function. Complete PANP is the best way to prevent urinary and sexual morbidity after rectal resection. The opposing goals of maximizing the chance for cure and minimizing morbidity must be individualized and balanced in each patient. Our data demonstrate that it is now possible to perform radical pelvic lymphadenectomy in the majority of patients with advanced rectal cancer with a minimum of voiding dysfunction. Preservation of sexual function in males is more difficult and depends on complete PANP and, as such, should be restricted to the group of patients with Dukes' A and B carcinomas.

Adult↗

A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. I. Immunological and histological studies.

Experimental autoimmune orchitis (EAO) was produced in C3H/He mice with as high as 100% incidence by two or three s.c. injections of 1 x 10(7) viable syngeneic testicular germ cells (TC) without resorting to adjuvants, Bordetella pertussis vaccine, or other immunological manipulations. On day 40 after the first injection of TC, the lesions induced were characterized by interstitial infiltration of inflammatory cells and severe hypospermatogenesis in the testis with resulting whole organ atrophy and, in contrast, by a complete lack of epididymitis. Immunological studies revealed that this form of immunization caused both delayed-type hypersensitivity and humoral antibody responses to syngeneic TC. We compared the susceptibilities to the induction of this type of EAO among six different strains of inbred mice comprising A/J, AKR, BALB/c, C3H/He, C57BL/6 and DBA/2 mice. All strains except for DBA/2 mice developed lesions of EAO to a greater or lesser extent, and severe disease was induced with high frequency in two strains, C3H/He and A/J. As this murine model of EAO can be induced without the use of Freund's complete adjuvant and B. pertussis vaccine, it is simply 'autoimmune' in nature and may provide new ways for further investigation into the immunological mechanisms which regulate deleterious autoimmune reactions to germ cell antigens leading to the male infertility.

Animals↗

A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. II. Immunohistochemical findings of fully-developed inflammatory lesion.

Previous studies demonstrated that experimental autoimmune orchitis (EAO) was produced in C3H/He mice with very high incidence by two or three subcutaneous injections of viable syngeneic testicular germ cells, without the use of any adjuvants or immunopotentiators and that the disease induced was characterized by a complete lack of epididymitis despite a definite orchitis with hypospermatogenesis. In this report, immunohistochemical characterization of immune cells in the fully-developed orchitic lesion was carried out using monoclonal antibodies and immunoperoxidase staining. Thy-1.2+ cells, Mac-1+ cells, B220+ cells and cytoplasmic Ig-bearing cells in the lesion were estimated to be approximately 30, 15, 20 and 30% of all inflammatory cells, respectively. Major phenotype of T cells in the lesion was CD4+ (approximately 85%) with the remainder (approximately 15%) being CD8+. The percentages of cytoplasmic IgG-, IgA- and IgM-bearing cells were estimated as approximately 35, 60 and 5% of all cytoplasmic Ig-bearing cells, respectively. Deposits of immunoglobulins and third component of complement were identified on the basement membrane of the seminiferous tubules, interstitium between the tubules, vessel endothelium and degenerated germ cells in the lesion. Circulating antibodies directed against the acrosomal portion of germ cells were detected in IgG and IgM classes but not in IgA class. Inflammatory cells (including macrophages, B cells and, probably, activated T cells) in the lesion were Ia+, but Leydig cells, Sertoli cells and germ cells did not stain for Ia at all.

Animals↗

Proliferation of an athymic mouse-derived T-cell clone on thymic stromal cells with interleukin-2.

An athymic mouse-derived CD4+8+ T-cell clone, N-9F, was established. It expresses both full length gamma and delta T-cell receptor (TcR) mRNA. N-9F clone was not maintained by interleukin-2 (IL-2) alone but required another soluble mediator(s), contained in concanavalin A-stimulated splenocyte culture supernatant, for its proliferation. By culturing N-9F on thymic stromal cells, [3H]thymidine incorporation was retained and expression of IL-2 receptor (IL-2R) was induced. This phenomenon was also observed on thymic stromal cells from H-2 allogeneic mice, but not on other cell types such as splenic adherent cells or fibroblasts. After addition of recombinant IL-2 into the N-9F culture with thymic stromal cells, N-9F showed enhanced IL-2R expression and greatly proliferated. The inability to detect any soluble factors in thymic stromal cell culture supernatant suggests that this interaction is mediated by direct cell contact between T and thymic stromal cells. Because a CD2-negative subclone, N-9.23, also proliferated on thymic stromal cells, there might exist a type of molecule other than CD2/LFA3 or TcR/MHC involved with thymic stroma and T-lymphocyte interaction.

Animals↗

Adjuvant hepatic intra-arterial chemotherapy after potentially curative hepatectomy for liver metastases from colorectal cancer: a pilot study.

The site most at risk of recurrence after hepatectomy is the remaining liver. Therefore a study was conducted of the use of hepatic intra-arterial and oral chemotherapy for colorectal metastases to prevent intrahepatic recurrence. Our regimen consisted of intra-arterial 5-fluorouracil (5-FU), mitomycin C (MMC) and oral 1-hexylcarbamoyl-5-fluorouracil (HCFU). Sixteen patients were treated. Median total dose of 5-FU was 8.1 g, MMC was 43 mg, and HCFU was 54 g, respectively. Median follow-up period was 21 months. The recurrence rate of the remaining liver was 31%. With respect to the number of hepatic metastases, there was no recurrence in patients with a single deposit. On the other hand, the intrahepatic recurrence rate of patients with multiple deposits was 45%. Of six patients with more than five hepatic deposits, however, only one patient had developed recurrent disease in the liver. Chemical sclerosing cholangitis (19%) was the most serious complication. Consequently, we propose that a prospective randomized trial should be carried out to establish the effects of this type of adjuvant chemotherapy to reduce possible recurrences in the remaining liver.

Adult↗

The role of lipocortin I in macrophage-mediated immunosuppression in tumor-bearing mice.

The soluble mediators and/or mechanisms involved in immunosuppression in tumor-bearing hosts are not well characterized, although macrophages have long been recognized as major participants. We have investigated the role of lipocortin I, a phospholipid-binding protein, in macrophage-mediated immunosuppression in tumor-bearing mice. Proliferation of splenic lymphocytes in response to the mitogens (PHA, Con A, LPS, and PWM) was severely suppressed in tumor (Sqc-NH-1 carcinoma)-bearing mice. This immunosuppression was associated with a decrease in T and B lymphocytes and an increase in macrophages in these spleens. Mac-2+ macrophages were found only in spleens from tumor-bearing mice. Splenic macrophages from tumor-bearing, but not normal, mice were responsible for this immunosuppression, as revealed by negative and positive selection experiments. The levels of lipocortin I mRNA expression were markedly increased in peripheral blood cells from tumor-bearing mice as compared with those from normal mice. Lipocortin I mRNA was strongly induced in splenic mononuclear cells from tumor-bearing mice. Furthermore, these cells displayed increased expression of lipocortin I protein, as judged by Western blot analysis with polyclonal anti-lipocortin I serum. Some nonimmune organs such as the heart, submaxillary gland, muscle, and bladder also displayed increased levels of lipocortin I mRNA expression in tumor-bearing mice. Mac-2+ macrophages among the splenic mononuclear cells in tumor-bearing mice expressed lipocortin I mRNA, as judged by negative and positive selection experiments. Most of these Mac-2+ macrophages also had Mac-1 and Mac-3 Ag. Lipocortin I protein was increased in the serum of tumor-bearing mice as compared with normal mice. The culture supernatants of splenic cells from tumor-bearing mice suppressed the mitogenic responses of splenic cells from normal mice, and addition of anti-lipocortin I antiserum inhibited this suppression. Furthermore, recombinant mouse lipocortin I suppressed mitogenic responses of splenic cells from normal mice. In summary, Mac-2+ macrophage-derived lipocortin I was largely involved in immunosuppression in tumor-bearing mice.

Animals↗

Differential effects of a single dose of cyclophosphamide on T cell subsets of the thymus and spleen in mice: flow cytofluorometry analysis.

Sequential changes in the distribution of lymphocyte subpopulations of the thymus and spleen in BALB/c mice (male, 8-weeks old) during 2 weeks after a single i.p. injection of cyclophosphamide (CY, 200 mg/kg body weight) were studied mainly through the use of CD4, CD8 and CD3-epsilon markers together with single- or two-color flow cytofluorometry. In the thymus on Day 2 after CY treatment, a marked decrease in the number and proportion of PNAhi, CD3- and CD4+CD8+ double positive (DP) subpopulation was observed in parallel with a marked reduction in the thymus weight, cortical area and total thymocyte number. This phenomenon might be associated with the decrease in the percentage of thymocytes at the S phase of the cell cycle on Day 1 and 2 after CY treatment, owing to the depletion of the rapidly dividing cells in DP subset. There was a significant reduction in the number and proportion in CD4+ single positive(SP) subset on Day 7. The cell number of CD8+SP subset continued to decrease during Day 7 to Day 14. This contrasted with the behaviors of DP, CD4+SP and CD4-CD8- double negative (DN) subsets in which a considerable recovery was attained by Day 14. The spleen from CY-treated mice showed a marked decrease in the DN subset and surface immunoglobulin-positive cells, perhaps B lymphocytes, in both the percentage and the absolute cell number on Days 2 and 7, which paralleled the marked reduction in its weight and total cell number. The absolute cell numbers of CD4+SP and CD8+SP subsets in the spleen were also reduced on Days 2 and 7. The reduction of the CD4+SP/CD8+SP ratio was found in the thymocytes on Days 2 and 7 but not in spleen cells. Our results suggest that the principal target cell population of CY is the PNAhi, CD3- and DP immature cortical thymocytes as well as splenic B cells. The sustained decrease in the number of CD8+SP thymocytes after CY treatment might be in part relevant to the potentiating effect of CY pretreatment on immune responses.

Animals↗