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Biomedical subjects

T Yano

Publications and source records attributed to T Yano.

At least 577 records · Page 32Linked to original sources

Oligoclonal T lymphocytes infiltrating human lung cancer tissues.

To clarify the nature of tumor-infiltrating lymphocytes (TILs), we investigated the possible clonality of the T cells in TILs freshly isolated from human primary lung cancer tissues by assessing the rearrangement pattern of the T-cell receptor (TCR) gene beta locus using Southern blotting. First, in phenotypic analysis, TILs represented different populations among corresponding peripheral blood lymphocytes (PBLs) with an increased proportion of CD20+ (B) cells as well as a decreased proportion of CD16+ (natural killer) cells, and a variable CD4/CD8 ratio. Considering the central role of T cells in immune responses, we analyzed TCR beta gene rearrangement patterns in TILs and corresponding PBLs from 12 patients. In 10 of the 12 cases, TILs showed one or more TCR gene rearrangement bands with a predominance of the C beta 2 gene, in which 2 types of common rearranged band were observed among the cases with different clinical profiles in terms of histological types and disease stage, with bands at about 9.5 kb in 7 and at 11.5 kb in 8 patients. On the other hand, predominant rearranged bands were hardly detected in corresponding PBLs except in 2 cases. From these results, we conclude that TILs in lung cancer tissues frequently contain oligoclonal T-cell populations, which were probably sensitized by relatively common antigens at the tumor sites.

Aged↗

Cytolytic potential of peripheral blood T-lymphocytes following adoptive immunotherapy with lymphokine-activated killer cells and low-dose interleukin 2.

In this study, we investigated the cytolytic activity of peripheral blood T-cells (PBT) obtained from nine patients with primary lung cancer treated by surgical adjuvant adoptive immunotherapy (AIT) with lymphokine-activated killer cells and low-dose recombinant interleukin 2 at the time of rebound lymphocytosis (24-48 h after AIT). In eight of nine patients, nonspecific cytotoxicity of peripheral blood lymphocytes significantly increased as compared with that of pre-AIT peripheral blood lymphocytes. However, purified PBT showed much less activity to kill tumor cells although they increased in number and were activated well in terms of increases in the expression of HLA-DR and interleukin 2 receptor. The cytolytic activity of post-AIT PBT was significantly enhanced when they were targeted to Fc receptor-bearing tumor cells (K562 or Daudi) with anti-CD3 (NU-T3) or anti-T-cell receptor (TCR)alpha beta (WT31) monoclonal antibody in all five patients examined. Phenotypically, the targeted cytotoxicity was predominantly mediated by CD8+ cells. The results indicated that in vivo-activated PBT by AIT could not exhibit direct cytotoxicity, but they acquired cytolytic potential, the effect of which was expressed by targeting to tumor cells.

Aged↗

Specific localization of phosphointermediate filament protein in the constricted area of dividing cells.

We developed antibodies pG1 and pG2 which recognize glial fibrillary acidic protein (GFAP) in its phosphorylated state. Antibodies pG1 and pG2 were produced against two synthetic peptides, Arg-Arg-Arg-Val-Thr-phosphoSer-Ala-Ala-Arg-Arg-phosphoSer (residues 3-13) and Pro-Gly-Pro-Arg-Leu-phosphoSer-Leu-Ala-Arg-Met-Pro (residues 29-39), respectively. The phosphorylation of these serine residues on the intact GFAP induces disassembly of glial filaments in vitro (Inagaki, M., Gonda, Y., Nishizawa, K., Kitamura, S., Sato, C., Ando, S., Tanabe, K., Kikuchi, K., Tsuiki, S., and Nishi, Y. (1990) J. Biol. Chem. 265, 4722-4729). Immunofluorescence and immunoblotting studies demonstrate that both antibodies react specifically with mitotic astroglial cells, thereby supporting the notion that increased phosphorylation during mitosis may directly influence intracellular organization of the glial filaments. The specific distribution pattern of the phosphoGFAP in the mitotic cells reveals that site-specific phosphorylation events may make way for the locally controlled breakdown of glial filaments in the constricted area, before the final separation of daughter cells.

Amino Acid Sequence↗

Immunohistologic detection of the epidermal growth factor receptor in human esophageal squamous cell carcinoma.

Epidermal growth factor receptor (EGF-R) expression was studied immunohistologically in 38 patients with esophageal squamous cell carcinoma. The EGF-R was faintly expressed in basal and parabasal layers of normal esophageal epithelia and in cancer nests of 20 patients; it was strongly expressed in all areas of dysplastic epithelia and in cancer nests of 18 patients. The patients with strongly expressed EGF-R had lymph node metastases more frequently, and their prognosis was poorer than those with faintly expressed EGF-R. The EGF-R expression showed a mosaic pattern in 17 patients and a diffuse pattern in 21 patients. The patients with a mosaic pattern had lymph node metastases more frequently and a worse prognosis than those with a diffuse pattern. Expression of EGF-R in metastatic lymph nodes was similar to that in strongly expressing areas of primary cancers with a mosaic pattern. Thus EGF-R expression may be an important indicator for malignancies of esophageal squamous cell carcinomas because primary cancer cells with strongly expressed EGF-R metastasize to lymph nodes more frequently.

Adult↗

Photodynamic therapy for rat pituitary tumor in vitro and in vivo using pheophorbide-a and white light.

This is the first report on the use of photodynamic therapy (PDT) for rat pituitary tumor in vivo. Rat pituitary tumor (GH3) cells were cultured, GH3 tumor was subcutaneously implanted in nude mice, and pheophorbide-a (Ph-a) and white light were prepared. Photocytotoxicity proportional to Ph-a concentration, intensity of irradiation, and incubation time was observed in vitro. Despite the delay in the disappearance of Ph-a from the tumor, Ph-a in the pituitary gland rapidly decreased after intravenous administration in vivo. Through PDT, the tumor grossly disappeared, the plasma levels of rat growth hormone secreted from the tumor also remarkably decreased, and the development of giantism was inhibited. These results indicate that PDT is effective against rat pituitary tumor.

Animals↗

Argon laser-assisted anastomoses in medium-size vessels: one-year follow-up.

Laser-assisted anastomosis of medium-size vessels can be performed with satisfactory short-term patency. This study was undertaken to evaluate patency and structural integrity up to 1 year. An argon laser was used to make bilateral femoral arteriovenous anastomoses in 12 dogs compared to conventional suture method in another 8 dogs. These anastomoses were evaluated for patency and aneurysm formation at 1 hour; 1, 2, 4, and 8 weeks; and 12 months after surgery. All anastomotic sites were patent and without aneurysmal change or luminal narrowing at all harvesting intervals. Histologic examination revealed that within 1 month laser anastomotic sites were almost completely healed and without intimal hyperplasia. In suture anastomoses, foreign-body reaction remained evident up to 1 year. Use of the argon laser for medium size vessel anastomoses resulted in excellent patency without aneurysm formation or intimal hyperplasia even in the long term. These data suggest promising clinical applications.

Anastomosis, Surgical↗

Development of a new culture system for human lymphokine-activated killer cells: comparison with a conventional static culture method.

We recently developed a new culture system based on dialysis perfusion (designated JCC-device) for the generation and expansion of human lymphokine-activated killer (LAK) cells (Murata et al., 1990). More recently we have scaled up the volume of the culture vessel of the JCC-device from 100 ml to 400 ml for clinical use. In the present study, using this new 400 ml JCC-device, we cultured human lymph node lymphocytes (LNL) obtained from 8 surgical patients with primary lung cancer, and investigated the cellular characteristics in comparison with a conventional batchwise culture system using tissue culture dishes. With the JCC-device, the cell density reached a maximum 2.7 x 10(7) cells/ml with greater than 90% viability by the appropriate exchange of perfusion medium and by making additions at the appropriate intervals for recombinant interleukin-2 (rIL-2). The expansion fold of LNL with the JCC-device, ranging 6.6- to 19.2-fold (mean 13.8-fold), was not significantly different from that in dish cultures. There was no marked difference in cell surface phenotypes between the two culture systems in 7 out of 8 cases. As for LAK activity of LNL, the JCC culture was either superior or equal in 4 out of 8 cases, but inferior in the other 4 cases to the conventional dish cultures. In the latter cases, the usage of serum for the JCC culture was limited, which might have resulted in the low LAK activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Count↗

Studies of serum-free medium for the generation of lymphokine-activated killer cells.

We examined a serum-free medium (designated as TYI 101) for the generation of lymphokine-activated killer (LAK) cells from human lymphocytes, regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL). TYI 101 medium consisted of, in addition to nutrient mixture, transferrin, insulin, fetuin, sodium selenite, 2-mercaptoethanol, o-phosphorylethanolamine, chick egg yolk and porcine kidney extract. These hormones were effective for supporting RLNL proliferation as assessed by (3H)-thymidine uptake. When human lymphocytes from two different sources were cultivated with recombinant interleukin 2 (rIL-2) in TYI 101 medium, LAK activity was generated. In cultures of PBL from a healthy donor, LAK cells were generated in TYI 101 medium as efficiently as in RPMI 1640 medium supplemented with 10% human AB-type serum (RPMI-AB). In cultures of RLNL from lung cancer patients, LAK activity obtained in TYI 101 medium was about sixty-five percent of that in RPMI-AB. However, the addition of a small amount of AB-type serum improved the generation of LAK activity, LAK cell expansion, and cell viability in TYI 101 medium. We conclude that TYI 101 medium can be used for the generation of LAK cells from human lymph node lymphocytes with supplementation of none or only a reduced amount of human serum.

Animals↗

A regimen of surgical adjuvant immunotherapy for cancer with interleukin 2 and lymphokine-activated killer cells. Basis, clinical toxicity, and immunomodulatory effects.

We designed a unique regimen of adoptive immunotherapy with lymphokine-activated killer (LAK) cells and recombinant interleukin 2 (rIL-2) for application with surgical adjuvant therapy of cancer. The regimen features the prolonged (6 consecutive days) s.c. administration of low-dose rIL-2 and the transfer of ex vivo generated LAK cells from regional lymph node lymphocytes, obtained at the time of surgical operation. According to this regimen, 5 patients with primary lung cancer received immunotherapy about 2 weeks after surgery (pulmonary lobectomy). Clinical toxicities included fever(5/5), fatigue(5/5), slight(less than 5%) weight gain(5/5), increase of pleural effusion at the lobectomy site(2/5), and edema formation(1/5). All toxicities reversed within 4 days after the completion of therapy. Rebound lymphocytosis after therapy ranged from 2.4 to 5.5-fold (mean, 4.3-fold) over the baseline. Peripheral blood lymphocytes obtained during this lymphocytosis exhibited in vitro LAK activity in 4 of 5 patients. Thus, the regimen is considered to be well-tolerable and immunologically active in regard to the postoperative state of the patients.

Adjuvants, Immunologic↗

Hemodynamic assessment of chronic venous insufficiency.

To study the pathogenesis of chronic venous insufficiency (CVI), photoplethysmography and strain-gauge plethysmography were simultaneously performed in 84 patients. Of the 128 limbs studied, 24 were normal, 64 had primary varicose veins and 40 had post-thrombotic syndrome. Venography was also performed in all patients. The results of this study indicate that reflux in the superficial veins is the main pathophysiology involved in the development of CVI, though incompetence of the perforators and deep veins plays some role. In post-thrombotic syndrome, however, CVI is mainly a sequel of deep venous incompetence, the condition being complicated by incompetent perforators and superficial venous reflux.

Chronic Disease↗

Angiocentric immunoproliferative lesions: a molecular analysis of eight cases.

Angiocentric immunoproliferative lesions (AILs) are believed to represent a unique type of extranodal malignant lymphoma on the basis of clinicopathologic and immunophenotypic evidence. However, molecular studies to assess clonality have been performed on a small number of cases. In this study we assessed the clonality of eight AILs using restriction fragment analysis, the Southern blot technique, and probes to assess the configuration of the T-cell receptor beta, gamma, and delta chain genes and the immunoglobulin heavy and K light chain genes. In addition, the presence of the Epstein-Barr (EB) viral genome was assessed by using both Southern blot analysis (seven cases) and polymerase chain reaction amplification (five cases). Our results demonstrate that gene rearrangements are rare in AILs. A clonal gene rearrangement was identified in only one case, a grade III AIL with a rearrangement of the T-cell receptor delta chain gene. In two additional AILs (both grade III), the EB viral genome was detected as a single band by Southern blot analysis with a probe derived from the terminal repeat region of the virus, suggesting that a single episomal configuration of the EB viral genome was present in each case, as would occur in a clonal population of infected cells. In the remaining cases there was no evidence of clonality, although EB sequences were detected in one of four cases using the polymerase chain reaction. The rarity or absence of gene rearrangements in AILs is difficult to explain if AILs are malignant, presumably monoclonal lymphomas. However, their frequent association with the EB virus may suggest an analogy between AILs and lymphoproliferative disorders that occur in immunosuppressed patients. These findings further emphasize the unique clinicopathologic aspects of AILs and may also be useful diagnostically in the differential diagnosis of lymphoproliferative disorders.

Adult↗

Mediators, initiating the inflammatory response, released in organ culture by full-thickness human skin explants exposed to the irritant, sulfur mustard.

Mediators released from injured human skin that initiate the inflammatory response have not been adequately identified. Organ culture of full-thickness skin explants enables us to do so, because injury to the skin can be made in vitro, eliminating the rapid leakage of serum and infiltration of leukocytes that occur in vivo. In our studies, the military vesicant sulfur mustard (SM) (10 microliters of a 0.01 to 1.0% dilution) was topically applied to injure the epidermis of the explant. Then, the explants were cultured in small Petri dishes, usually for 18 h at 36 degrees C, and the organ-culture fluids were assayed for various inflammatory mediators. We found that the culture fluids from SM-exposed and control explants contained similar amounts of angiotensin-converting enzyme, trypsin-like and chymotrypsin-like proteases, acid phosphatase, beta-glucuronidase, beta-galactosidase, lysozyme, deoxyribonuclease, ribonuclease, interleukin 1, and lactic dehydrogenase. However, the culture fluids from SM-exposed explants contained increased amounts of histamine and plasminogen-activating activity, and often prostaglandin E2, when compared to culture fluids from control explants. After 3 to 4 d in culture, full-thickness human skin explants, when exposed to 0.2% SM (but not when exposed to 1.0% SM), sometimes showed separation of the epidermis and increased collagenase activity (i.e., hydroxyproline release). Thus, histamine (from local mast cells), and prostaglandin E2 and plasminogen-activating activity (probably from both mast cells and epidermal cells) are apparently involved in early mediation of the inflammatory response.

Administration, Cutaneous↗

A common V delta 2-D delta 2-D delta 3 T cell receptor gene rearrangement in precursor B acute lymphoblastic leukaemia.

Despite their apparent commitment to the B lymphocytic lineage, human precursor B cell acute lymphoblastic leukaemias (ALL) frequently rearrange their T cell antigen receptor (TCR) alpha, beta and gamma chain genes. Since these three genes are active sites of rearrangement in precursor B cell neoplasms, it seemed that the recently discovered fourth TCR gene, delta, might be similarly rearranged. To investigate this possibility, a series of precursor B cell leukaemias was analysed for rearrangements at the delta chain gene locus, using probes of the variable, joining, and constant regions of the delta chain gene. The majority of precursor B cell ALLs in this series (25/32, 78%) showed rearrangement or deletion of one or more TCR delta genes. This contrasts sharply with a series of 16 mature B cell neoplasms (chronic lymphocytic leukaemia) in which no TCR delta gene rearrangements were detected. An unusual TCR delta rearrangement, rarely observed in normal or neoplastic T cells, was seen in the majority (14/18) of precursor B cell ALLs with TCR delta rearrangements. In contrast to the utilization ov V delta 1 in T cell ALL, detailed restriction mapping of precursor B ALL revealed an incomplete rearrangement without involvement of J delta segments. Direct genomic sequencing was performed on one example and demonstrated a nonproductive V delta 2-D delta 2-D delta 3 recombination in this precursor B ALL. We conclude that the TCR delta chain gene is an active locus in precursor B cell neoplasia, involves an unusual type of rearrangement and provides a clonal tumour marker for diagnosis of precursor B ALL.

Base Sequence↗

[A mechanism of usefulness of treatment with erythromycin for diffuse panbronchiolitis].

The clinical usefulness of treatment with erythromycin for diffuse panbronchiolitis (DPB) patients have been well reported to date, although its mechanisms remain unknown. In a previous study, we demonstrated that DPB patients were found to have large percentages of neutrophils in their lower respiratory tracts and suggested that neutrophils play an important role in the pathogenesis of DPB (Chest 99: 917-923, 1990). While in vitro and in vivo studies have demonstrated that erythromycin decreases neutrophils directed migration. In the present study, we performed bronchoalveolar lavage (BAL) on eight patients with DPB to clarify the cell populations in the lower respiratory tract before and after treatment with erythromycin. Neutrophils percentages in BAL fluid were significantly reduced after treatment with erythromycin (54.3 +/- 22.4% to 13.1 +/- 13.5%, p less than 0.01). No significant variance of BAL lymphocyte percentages was demonstrated after treatment with erythromycin. These results suggest that a main mechanism of clinical usefulness of treatment with erythromycin for DPB may be inhibition of neutrophils migration into the lower respiratory tract instead of intrapulmonary bactericidal activity against organisms.

Adolescent↗

[A case of mediastinal abscess due to Enterococcus faecalis accompanied with superior vena cava syndrome].

Superior vena cava (SVC) syndrome caused by benign diseases is rare. We reported a case of mediastinal abscess due to Enterococcus faecalis (E. faecalis) accompanied with SVC syndrome and reviewed the literature on this particular condition. A 38-year-old female with swelling of the neck and dilatation of cervical vein was admitted to our hospital, being diagnosed as having a SVC syndrome. Chest roentgenogram revealed an enlargement of the right upper mediastinum and a massive infiltration in the right upper lung field. CT scan demonstrated a mass with central necrosis occupying the right upper mediastinum and stenosis of superior vena cava. Further conformation of the stenosis of vena cava was made by means of venography. E. faecalis was recovered from the pus aspirated from the mediastinal abscess, and a definitive diagnosis of SVC syndrome caused by mediastinal abscess due to E. faecalis was made. There has been no report, to our knowledge, on mediastinal abscess evolving SVC syndrome in which E. faecalis was identified as a causative organism. The present case indicates that a benign disease such as lung abscess should be considered to be a possible cause of SVC syndrome in addition to other frequent malignant diseases.

Abscess↗

[Role of transiently accumulated neutrophils in the lung of hamster in development of pneumonia due to Mycoplasma pneumoniae].

The importance of Mycoplasma pneumoniae as a pathogen of human infectious diseases, particularly of respiratory infections, has been well recognized. However, the details of the mechanism through which lung tissue damages are produced in mycoplasmal infection has not been fully understood. It has been pointed out that beside the direct invasive process certain immunological responses to the deposited microbes are crucial in development of mycoplasmal pneumonia. In the present study, we aimed at elucidating the role of neutrophils in producing pneumonia due to Mycoplasma pneumoniae in hamsters. For this purpose, hamsters were divided into two groups; the one not pretreated and infected with Mycoplasma pneumoniae and the other immunosuppressed by 60Co irradiation and infected. A serial determination of the numbers of mycoplasmal cells recovered from the treacheal tissue and bronchoalveolar lavage fluid (BALF) and analysis of cellular components in BALFs were carried out. The severity and the nature of pathological changes produced in the lungs were evaluated and scored on the basis of microscopic findings. As a result, it was found that the numbers of mycoplasmal cells recovered from both tracheal tissues and BALFs reached maximum on the seventh day of infection in both groups and decreased rapidly. There no apparent difference was found between the two groups in number of cells recovered. In the not-irradiated control groups, the percentage of polymorphonuclear leukocytes (PMNs) in BALF was very high on the seventh day and then they were replaced by lymphocytes by the 21st day of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Elastase activity in bronchoalveolar lavage fluid from patients with diffuse panbronchiolitis].

The clinical and pathological features of diffuse panbronchiolitis (DPB) have been well reported to date though its pathogenesis remains unknown. This study was designed to evaluate the protease antiprotease imbalance in patients with DPB. For this purpose, we performed bronchoalveolar lavage (BAL) in sixteen patients with DPB, twelve patients with chronic bronchitis (CB) and control subjects (nine smokers and eleven non-smokers), and determined elastase activity and alpha 1 antitrypsin (alpha 1 AT) concentration in bronchoalveolar lavage fluid (BALF). Elastase activity was measured using a synthetic substrate, succinyl-tri-L-alanine-p-nitroanilide. BALF from eleven of sixteen patients with DPB showed elastase activity. However, only two of twelve patients with CB showed elastase activity, and control subjects did not show any elastase activity in BALF. Although alpha 1 AT concentration is elevated in BALF from patients with DPB, it is assumed that elastase burden exceeded the elastase inhibitory capacity of alpha 1 AT in BALF. The percentage of neutrophils in BALF correlated significantly with elastase activity which was inhibited by DFP, but not by EDTA. These data revealed that the elastase in BALF was a serine protease of neutrophil origin. In five DPB-patients treated with low-dose long-term erythromycin chemotherapy, elastase activity in BALF decreased significantly. The above mentioned findings suggest that the neutrophil elastase plays an important role in the pathogenesis of DPB, and the mode of action of erythromycin on DPB is to decrease the elastase burden.

Adolescent↗