Biomedical subjects

T Osaki

Publications and source records attributed to T Osaki.

At least 181 records · Page 10Linked to original sources

PubMed1993

Effects of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and monocytes on lymphokine-activated killer (LAK) induction from natural killer (NK) cells and T lymphocytes.

Roles of monocytes and cytokines were investigated on LAK induction from T and NK cells. Monocytes augmented more T-LAK induction than did NK-LAK. Expression of IL-1 beta, TNF-alpha and interferon-gamma (IFN-gamma)-mRNA and their cytokine production were superior in NK cells compared with T cells in parallel with their LAK activities. An increase of TNF-alpha, IL-1 beta and IFN-gamma production was induced by co-culturing NK or T cells with autologous monocytes. The augmentation of T cell cytokine production and T-LAK activity by monocytes was more prominent than that of NK cells. TNF-alpha and IL-1 beta were generated 24 h after IL-2 stimulation, and these cytokines were able to almost substitute for monocytes in LAK induction. Conversely, LAK induction was almost completely suppressed by both anti-IL-1 beta and anti-TNF-alpha antibodies, if they were added within 24 h after the start of the LAK induction. IFN-gamma, which was produced at a later stage, scarcely affected LAK induction in spite of the cooperation with TNF-alpha. The results obtained indicate conclusively that the superiority of NK-LAK depends on their superior productivity of both IL-1 beta and TNF-alpha, and that the up-regulation of LAK induction by monocytes is largely due to the enhanced generation of both cytokines.

Cytokines↗

PubMed1993

Leukocyte dysfunction in oral mucous membrane diseases.

Leukocyte functions were investigated in patients with oral candidiasis (OC), recurrent aphthous ulcers (RAU) and oral lichen planus (OLP). Blastogenesis and lymphokine-activated killer (LAK) activity were decreased in RAU and OLP compared with healthy controls, and lymphocytes from patients with OC exhibited the lowest blastogenesis and LAK activity. Neutrophil superoxide (O2-) generation showed the following relationship: healthy controls > RAU congruent to OLP > OC patients. No great differences in phagocytosis or natural killer (NK) activity were observed among patients and healthy controls, although NK activity in controls was slightly higher than in patients. In OC, all suppressed leukocyte functions improved with the disappearance of the clinical manifestations. However, in RAU there were no significant differences before and after treatment except for O2- generation. These results indicate that OC tends to occur in individuals predisposed to fungal infections and that the pathophysiology of both RAU and OLP is associated with leukocyte suppression.

Adolescent↗

PubMed1993

Prevalence of diabetes mellitus in odontogenic infections and oral candidiasis: an analysis of neutrophil suppression.

The prevalence of diabetes mellitus (DM) in odontogenic infections and oral candidiasis was examined, and influences of DM on the clinical manifestations of the infections and neutrophil functions were investigated. Among 21 severe and 221 mild odontogenic infections, DM was detected in 5 cases in each group. Of 64 cases of symptomatic oral candidiasis, 8 cases were complicated with DM which was detected by blood examination during treatment. During the period of infection, the mean fasting blood sugar level was 16.0 +/- 4.4 and 9.8 +/- 1.2 mmol/l in the DM-complicated odontogenic infections and candidiasis, respectively. All white blood counts, C-reactive protein levels and erythrocyte sedimentation rates were more elevated in DM(+) odontogenic infection cases than in DM(-) ones. In DM(+) candidiasis, hyposalivation (0.79 +/- 0.54 ml/10 min) was observed. The polymorphonuclear leukocytes from diabetic patients, especially those with candidiasis, produced less free oxygen radicals and exhibited reduced phagocytosis and intracellular killing of Candida cells associated with this reduced O2- generation during the infection. These suppressed neutrophil functions increased after treatment but did not reach control levels. These results indicate that DM is a predisposing condition for odontogenic infections and oral candidiasis, that DM-complicated infections become severe because of neutrophil suppression, and that examination of blood sugar level should be essential for patients with oral infections.

Adult↗

PubMed1993

Immunological investigation of adult patients with primary herpes simplex virus-1 infection.

Peripheral blood mononuclear cell parameters were examined in 17 adult patients with primary herpes simplex virus-1 (HSV-1) infection. Two-color flow cytometry revealed an increase in HLA-DR+ T cell and Leu8+ T cell subsets, and a decrease in CD57+CD16+ subset in the patients. In the symptomatic phase of HSV-1 infection, serum interferon gamma (IFN-gamma) level increased in many patients, and the mean serum level in the patients (0.26 +/- 0.12 U/ml) was significantly higher than the mean control level (0.14 +/- 0.06 U/ml). Soluble intercellular adhesion molecule-1 (sICAM-1) in patients' serum also was increased to a mean level of 398 +/- 130 ng/ml at the first visit. Both the IFN-gamma and sICAM-1 levels fell to near the control levels after the disappearance of oral inflammation. Natural killer (NK) activity was at first increased (mean 46.1 +/- 17.9%), and later decreased to the control level (mean 38.4 +/- 10.6%). In contrast, lymphokine activated killer (LAK) activity at the first visit (mean 53.2 +/- 15.7%) was significantly lower than the control level (mean 69.5 +/- 10.3%). PHA- or ConA-stimulated lymphocytes from the patients incorporated less thymidine than control lymphocytes. These reduced lymphocyte reactivities recovered to the control levels after the disappearance of the acute infection. These results indicate some of the characteristics of lymphocyte pathophysiology in primary HSV-1 infection.

Adult↗

PubMed1993

[Evaluation of results following thymectomy in myasthenia gravis].

Sixty-nine patients with generalized myasthenia gravis underwent thymectomy consecutively between 1980 and 1991 and were evaluated 1 month to 120 months after operation. Extended thymectomy was performed in 43 patients and other procedures in 26. The effect of thymectomy were as follows: 14.5% of the patients achieved complete remission (no symptoms, no medication), 73.9% showed improvement; in total 88.4% had palliation. The long-term changes of the remission rate at one and five years after operation were 11.5% and 19.2%, and showed a delayed remission. The long-term changes of the improvement and palliation rate were 55.7% and 67.2% at one year, 69.2% and 88.5% at five years after operation. There was significant difference in remission rate according to age at the time of operation and age of onset, but the response did not depend on sex, presence or absence of thymoma, preoperative duration of illness, Osserman's type and operative procedure.

Adolescent↗

PubMed1992

Midline malignant B-cell lymphoma with leukemic transformation.

This article presents a case of lethal midline granuloma on the palate of a 44-year-old woman, which had been identified histologically as B-cell lymphoma with leukemic transformation in the terminal stages. At the first visit, physical and laboratory examinations showed no remarkable findings except for a necrotizing ulcer of the palate, and the biopsy specimens only showed massive inflammatory cell infiltration and necrosis of the granulation tissue. There was a short-term resolution after treatment with cyclophosphamide and prednisolone, but the disease reactivated and the necrotic ulcerative lesion progressively advanced into the nasal cavity. Specimens from the third biopsy exhibited histologic features that were consistent with malignant lymphoma of the diffuse, mixed B-cell type. Chemotherapy with the regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone was adopted but was interrupted after a short time because of bone marrow suppression. Subsequently, large numbers of enlarged abnormal lymphocytes with a few vacuoles in the cytoplasm appeared in the circulating blood, indicating leukemic transformation of the midline lymphoma. The patient died on the seventh day after the initiation of chemotherapy. In the presentation of this case, the authors mention clinically important matters regarding midline lethal lymphoma and briefly discuss the pathophysiology and pathogenesis.

Adult↗

PubMed1992

Generation of a small cell lung cancer variant resistant to lymphokine-activated killer (LAK) cells: association with resistance to a LAK cell-derived, cytostatic factor.

Cells of OS2-RA, a human small cell lung cancer line sensitive to lymphokine-activated killer (LAK) cells, were repeatedly cocultured with human LAK cells. Fourteen cycles of the coculture produced a variant, termed OS2-RA-R, capable of growing successfully in the presence of LAK cells. OS2-RA-R showed a moderate resistance to lysis by LAK cells in 4-h 51Cr release assays. OS2-RA-R acted positively as a cold target for lysis of OS2-RA by LAK cells, suggesting no loss of the binding site for LAK cells on the cell surface of the variant. On the other hand, LAK cells were shown to produce a factor capable of suppressing the proliferation of OS2-RA and certain other cell lines but not lymphocytes. Interestingly, OS2-RA-R exhibited a substantial resistance to the cytostatic activity of LAK cell supernatants. The cytostatic factor, eluted at the 57-kDa fraction in gel filtration, showed no activity of interleukin 1, gamma-interferon, transforming growth factor beta, or tumor necrosis factor. These results suggest that LAK cells exhibit antitumor activity through not only rapid cytolysis but also slow-acting cytokine production, and the successful growth of OS2-RA-R in a coculture with LAK cells is the result of acquiring resistance to these two different LAK cell phenomena.

Animals↗

PubMed1992

Complete excision and panpleuropneumonectomy resulting in long-term survival for a teenager with invasive thymoma: report of a case.

An 18-year-old girl with invasive thymoma and pleural dissemination underwent a complete removal of the tumor with combined resection of the pericardium and a panpleuropneumonectomy of the left lung. At the time of writing, 70 months later, she was doing well under the classification of grade I performance status with no signs of recurrence. Thus, complete surgical removal of this tumor can prolong the survival time of patients with invasive thymoma and pleural dissemination.

Adolescent↗

PubMed1992

Induction of lymphokine-activated killer cells with low-dose interleukin 2 and interferon-gamma in oral cancer patients.

Lymphokine-activated killer (LAK) cells were induced with low-dose recombinant interleukin 2 (rIL-2) and recombinant interferon-gamma (IFN-gamma) in 28 oral carcinoma patients. The patients received daily intravenous injections of rIL-2 (1.2 x 10(5) U/m2) and rIFN-gamma (7.0 x 10(4) U/m2), and both natural killer (NK) and LAK activities were periodically examined. A significant increase in CD16+CD57+ and CD16+CD57- NK subsets was observed after the induction. An increase in the T-cell population was also found, with a significant increase in CD3+HLA-DR+, CD8+Leu8-, and CD4+Leu8- cells. Significant increases in NK activity, from the original level of 32.0 +/- 13.7 to 49.9 +/- 15.2%, and LAK activity, from 4.8 +/- 3.5 to 11.0 +/- 6.1%, at Day 7 were observed. Both activities were maintained at high levels during the cytokine injections, but greater enhancement of the killing activities could not be obtained subsequently. When NK and LAK activities were investigated in each subpopulation of CD3- and CD16- cells, no remarkable cytotoxic activity could be observed before induction in any subset without NK activity in CD3- cells (31.1 +/- 14.3%). At Day 7, NK activity of CD16- cells increased up to 21.4 +/- 14.9%, accompanied by an increase in CD3(-)-cell activity (54.5 +/- 20.6%). LAK activities of both subsets were also enhanced, with activity at Day 7 of 6.5 +/- 5.6 and 9.4 +/- 6.6% in CD16- and CD3- cells, respectively. These increased activities were maintained at the same level during the induction. Phorbol myristate acetate-induced polymorphonuclear leukocyte (PMNL) O2-generation was significantly increased, from the original 81.1 +/- 28.1 to 95.6 +/- 34.9 pmol/min/10(4) cells, after 1 week of treatment. Protein kinase C activity in the cytosol decreased, and the activity in the membrane fraction conversely increased. No remarkable adverse effects except for mild fever were observed. Together with LAK induction ability and PMNL enhancement, with scarce toxicity, a combination of low-dose rIL-2 and rIFN-gamma is thought to be useful in cancer treatments.

Antigens, CD↗

PubMed1992

Upregulatory effects of cefpimizole natrium on human leukocytes.

Cefpimizole natrium (CPIZ), an antibiotic belonging to the cephalosporins, was examined regarding its influence on neutrophil functions. Neutrophil superoxide (O2-) generation increased by intravenous CPIZ in patients with maxillofacial diseases. In vitro examination revealed that CPIZ directly stimulates neutrophils to generate O2- in a dose-dependent manner, though the induction ability is not as strong as phorbol myristate acetate (PMA). Protein kinase C (PKC) activity in the neutrophil plasma membrane increased after CPIZ treatment, while the activity in the cytosol fraction decreased. CPIZ cooperated with biological response modifiers (BRMs) such as sizofilan, lentinan, OK-432, rIL-2 and rIFN-gamma in neutrophil O2- generation. Non-specific cytotoxicity against K562 cells and candida cells was also enhanced by neutrophil pretreatment with both CPIZ and one of the BRMs except for sizofilan and rIL-2. From these results it can be concluded that CPIZ directly enhanced neutrophil O2- generation and that these CPIZ activations are further beneficial to protection against bacterial infections.

Cells, Cultured↗

PubMed1992

Electron microscopic study on cell-to-cell interactions in oral lichen planus.

Ultrastructural analysis of oral lichen planus was performed in 18 cases, focusing on cell-to-cell interactions. In the peripheral portion of the lesion, the most consistent findings were a widening of intercellular spaces, separation of the basement membrane (BM) from basal cells and scarce inflammatory cells. In the central portion of the lesions basal cells and BM showed severe damage and numerous inflammatory cells infiltrated into both the epithelium and subepithelial stroma. The infiltrates predominantly consisted of T-lymphocytes, a few Langerhans cells (LC) and macrophages. Most lymphocytes were large and positive for CD45RO. Dendritic LC and macrophages with cytoplasm containing abundant organelles were seen in the epithelium and subepithelial stroma, respectively. Close contacts of lymphocytes with LCs, macrophages and also with keratinocytes were sometimes observed in the central portion. In the subepithelial stroma, some lymphocytes contacted an HLA-DR+ dendritic cell, which was possibly a macrophage, forming a rosette-like arrangement. Conjugations between CD4 cells and dendritic cells (possibly LC) and also between CD8 cells and basal cells were observed in the epithelium. These T cells were large in size, and the CD8 cells which made contact with degenerated keratinocytes possessed cytoplasm containing numerous polarized organelles and a nucleus toward and contrary to the contact side, respectively. These lymphocytes expressed LFA-1 on the cell surface, and many basal cells exhibited ICAM-1. These findings indicate that T cells may receive information from LC and macrophages concerning degenerative keratinocytes, and that informed T cells attack perhaps the keratinocytes.

Basement Membrane↗

PubMed1992

High sensitivity to peripheral blood lymphocytes and low HLA-class I antigen expression of small cell lung cancer cell lines with diverse chemo-radiosensitivity.

Three cell lines of small cell lung cancer (SCLC), which were established from specimens of untreated primary tumors biopsied by diagnostic bronchofiberscopy, were analyzed for immunological characteristics. These cell lines showed considerable heterogeneity in chemo-radiosensitivity, which was well correlated with clinical responses of the respective tumors, but their HLA-class I antigen expressions were equally depressed and they were susceptible to peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells, irrespective of their diverse chemo-radiosensitivity. Treatment of the cell lines with recombinant immune interferon (rIFN-gamma) increased their HLA-class I antigen expression and conversely depressed PBL sensitivity but not LAK sensitivity. This inverse relationship between HLA-class I expression and PBL susceptibility was also demonstrated using other pairs of autologous PBL and SCLC cell lines. rIFN-gamma changed neither HLA-class II antigen nor SCLC-specific antigen expression under the same experimental conditions. In vitro immunization of allogeneic peripheral blood lymphocytes with rIFN-gamma-treated SCLC cells induced allo-specific killer cells which lysed rIFN-gamma-treated more strongly than non-treated SCLC cells. These results suggest that reduced HLA-class I antigen expression of SCLC could protect the cancer from attack of killer T cells in spite of the higher sensitivity to PBL or LAK cells.

Antigens, Surface↗

PubMed1992

Changes in the Ki-67 labeling rates of head and neck squamous cell carcinomas during preoperative radiation therapy.

Immunostaining with Ki-67 monoclonal antibody was performed on frozen sections of biopsy specimens obtained before and during preoperative radiation therapy from 21 patients with head and neck squamous cell carcinoma. The Ki-67 labeling rates before radiation therapy and at radiation doses of 10 and 20 Gy ranged from 21 to 71% (mean: 35.0%), from 7 to 49% (mean: 25.8%) and from 1 to 44% (mean: 14.8%), respectively. One of the 2 patients whose tumors showing Ki-67 labeling rates of greater than 48% (mean +1 SD) before radiation therapy suffered local relapse shortly after the treatment. Moreover, tumors with rapidly decreased Ki-67 labeling rates (lower than 3%) at radiation doses of 20 Gy were related to poor clinical outcome: 4 out of 6 patients whose tumors showed Ki-67 labeling rates below 3% (mean -1 SD) at 20 Gy of irradiation had local relapses or showed distant metastases. These findings indicate that immunostaining with Ki-67 monoclonal antibody of biopsy specimens of head and neck squamous cell carcinoma, before and during radiation therapy, is very useful in assessing the clinical outcome of the patients.

Adult↗

PubMed1992

[Panpleuropneumonectomy for primary lung cancer patients with pleural dissemination].

Twelve patients of non-small cell lung cancer with carcinomatous pleuritis were subjected to panpleuropneumonectomy between June 1981 and December 1988. The median survival time was 13 months. One-year and 3-year survival rates were 52% and 26%, respectively. There was no significant difference in prognosis compared with the results of other modality therapies such as pleurodesis with talc and tube drainage for pleural effusion. After panpleuropneumonectomy the patients were divided into the group with only pleural dissemination and the one with pleural effusion. The median survival time in the group of pleural dissemination was 14 months. The three-year survival rate was 50%. The one patient survived for 51 months and the other for 45 months. The median survival time of patients with pleural effusion was 4 months without over 1-year survivor. The statistically significant difference was found between the two groups (p less than 0.05). We concluded that panpleuropneumonectomy is indicated only for the patients of non-small cell lung cancer with diffuse pleural dissemination and no pleural effusion.

Adult↗

PubMed1992

[Evaluation of surgical treatment of spontaneous pneumothorax--assessment of postoperative recurrence and quality of life].

To assess the effect of surgical treatment for spontaneous pneumothorax, including the evaluation of the quality of postoperative life by a questionnaire method, we examined 139 patients with spontaneous pneumothorax who underwent the surgical treatment. The operation was performed 149 times and 154 sides for these patients. Of these, 95 cases (65.2%) were the first episode of the disease, since we often chose surgical treatment even for the first attack of the disease. Postoperative recurrence was seen in only one case (0.6%). Operative complications included 4 cases of empyema (in two of them requiring reoperation) and 18 cases of wound infection. The most common postoperative complaints were post-thoracotomy pain in 12 cases (12.6%), disturbance of sensation in the scar in 9 (9.5%), and limitation of exercise in 9 (9.5%). Four patients (4.2%) suffered from these symptoms and had difficulty in daily life. Forty-seven patients (49.5%) had a fear of recurrence. Quality of postoperative life was almost satisfactory. From the viewpoints of both prevention of the recurrence and postoperative quality of life, the surgical treatment is effective and safe method. We advocate the surgical treatment as the first choice of the treatment even in case of the first episode of the disease, especially in patients with high activities in social life.

Adolescent↗

PubMed1991

Two monoclonal antibodies against small-cell lung cancer show existence of synergism in binding.

Murine IgG1 monoclonal antibodies (mAbs), ITK-2 and ITK-3, were generated against a small-cell lung cancer (SCLC) cell line. Enzyme-linked immunosorbent assay using a variety of established cell lines as substrates, immunoperoxidase staining of freshly frozen tissue sections, and fluorescence-activated cell sorter analysis of peripheral blood leukocytes showed that these mAbs recognize a part of the SCLC-associated cluster 1 antigen. In immunoprecipitation studies, both ITK-2 and ITK-3 bound to a 145-kDa glycoprotein of SCLC cell membrane extracts, as did MOC-1 and NKH-1, which both recognize the cluster 1 antigen. However, because the binding of 125I-labeled ITK-2 to SCLC cells was not inhibited by MOC-1 or NKH-1, the binding site of ITK-2 on SCLC cells appeared to be different from that of either MOC-1 or NKH-1. Unexpectedly, binding of 125I-labeled ITK-2 to SCLC cells increased in the presence of ITK-3. This ITK-3-induced increase in ITK-2 binding was due partly to an increase in the number of binding sites for ITK-2 on SCLC cells. Addition of ITK-3 may, therefore, improve the effectiveness of ITK-2-based tumor detection or therapy.

Antibodies, Monoclonal↗

PubMed1991

Immunoregulatory effects of sizofiran (SPG) on lymphocytes and polymorphonuclear leukocytes.

The effect of SPG on leukocytes has been studied in 20 patients with oral carcinoma and the actions have been analysed in vitro. SPG 1 mg/kg was administered intramuscularly twice weekly. Peripheral venous blood was collected before, and 1 week and 2 weeks after the initiation of SPG treatment. Both CD16+CD57- and CD16-CD57+ cell populations were significantly increased after treatment, but no T cell subset varied. While enhancement of lymphokine-activated killer activity could not be found, an increase in natural killer (NK) activity was observed in 15 of the subjects, and the mean NK level was significantly increased from an initial 34.7 +/- 18.7% to 46.4 +/- 16.5% after two weeks of injections. O2-production by polymorphonuclear leukocytes (PMNL) was stimulated 6 h after SPG injection. When PMNL were treated in vitro with SPG 32 micrograms/ml, enhanced O2-generation was induced and protein kinase C (PKC) activity in a membrane fraction increased. SPG did not directly affect non-specific PMNL killing of K562 cells or antibody-dependent cell mediated cytotoxicity against Raji cells, but non-specific PMNL killing was enhanced by culture-conditioned medium from peripheral blood mononuclear cells (PBMC) containing 10 micrograms/ml SPG. Interleukin-1 beta, -3, -4, -6, tumour necrosis factor-alpha, granulocyte-macrophage colony stimulating factor and IFN-gamma levels in the conditioned medium were not increased compared with medium from PBMC not treated with SPG. No clear increase of these cytokines was found in serum from the SPG-treated patients. From the above results, enhancement of PMNL O2-generation by SPG seems to be a direct action of SPG, but the mechanism of elevation of the non-specific killing activity of PMNL and NK cells is not known. Perhaps other cytokines than those assayed have participated in increasing non-specific cytotoxicity.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1991

Serum cytokine levels in patients with oral mucous membrane disorders.

Serum cytokine levels were examined in 18 oral squamous cell carcinoma (SCC), 26 lichen planus (OLP), 20 recurrent aphthous stomatitis (RAS), 8 herpetic gingivostomatitis (HGS), 16 pseudomembrane candidiasis (PMC) and 19 acute bacterial infection (ABI) cases. All SCC and most PMC patients possessed clear serum IL-3. No clear increase of IL-4 was observed in most cases though over 20 pg/ml were found in a few OLP, RAS and ABI. ABI exhibited the highest IL-6, and the cytokine level was lower in RAS, PMC, HGS and OLP in this order. Suppressed IL-6 activity was elevated with improvement of HGS lesion. TNF-alpha increased in 9 OLP, but the levels were below 100 pg/ml in all cases. Most SCC possessed higher GM-CSF activity than the controls. Increase of the cytokine corresponding with improvement of the oral lesion was seen in HGS, but not in OLP. From these results, each serum cytokine seems to reflect a characteristic pathophysiology of individual oral disorder.

Abscess↗