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Biomedical subjects

A Nagashima

Publications and source records attributed to A Nagashima.

At least 73 records · Page 4Linked to original sources

Cardiovascular roles of tachykinin peptides in the nucleus tractus solitarii of rats.

Unilateral removal of the afferent fibers of the IXth and Xth cranial nerve (nodose ganglionectomy) caused significant decrease in the content of substance P-like immunoreactivity (SP-LI) and neurokinin A-like immunoreactivity (NKA-LI) in the nucleus tractus solitarii (NTS) of rats. Microinjection of SP (1 ng) or NKA (10-100 ng) into the NTS caused prompt, transient hypotension and bradycardia, suggesting that SP and NKA may be neurotransmitters of the baroreceptor reflex in the NTS. NKB-like immunoreactivity (NKB-LI) was also detected in the NTS of rats by radioimmunoassay, but its content in the NTS was not affected by unilateral nodose ganglionectomy. The microinjection of 1-10 ng of suc-[Asp5, Me-Phe8]-SP(6-11) (senktide, a selective neurokinin B receptor peptide) into the NTS caused long-lasting hypertension and tachycardia. These results indicate that NKB may also be a neuromodulator on cardiovascular responses in the NTS.

Animals↗

[An assessment of extended lymphadenectomy including cervical node dissection for cancer of the thoracic esophagus].

An extended lymphadenectomy including cervical node dissection is one of the most difficult operations, therefore its merits and demerits should be assessed in order to evaluate whether it has the significance of extended radical operation or not. Extended lymphadenectomies including cervical node dissection became to be the standard procedures of lymphadenectomy for cases with cancer of the thoracic esophagus from 1986, and were carried out in 42 cases. Survival rates, disease free survival rates, sites of recurrences and incidences of postoperative complications were compared with the of cases with conventional lymphadenectomy excluding cervical node dissection. Concerning over all survival rates, no significant differences were observed between extended and conventional groups. However only in cases of stage 0 I II, significant difference in survival rates were observed between two groups. Therefore based on our experience, the merit of extended lymphadenectomy was observed only in stage 0 I II cases which had no lymph node metastasis. Concerning the incidence of postoperative complications, no significant differences were observed between two groups, therefore the significance of proceeding extended lymphadenectomy was confirmed.

Esophageal Neoplasms↗

The 28k and 70k dalton polypeptide components of mouse Ra-reactive factor are responsible for bactericidal activity.

Ra-reactive factor is a complement-dependent bactericidal factor that reacts specifically with Ra chemotype strains of Salmonella, and is ubiquitous in sera of a wide variety of vertebrates. Here we prepared an antiserum by immunizing rabbit with mouse Ra-reactive factor. This serum neutralized markedly the bactericidal activity of the factor. This action of the antiserum was inhibited by the factor whose bactericidal activity has been inactivated by heating for 30 min at 55 degrees C. Component polypeptides with apparent molecular weights of 28k and 70k in the factor were separated by SDS-polyacrylamide gel electrophoresis. They were also found to inhibit the antiserum activity. This indicates that these polypeptides carry the active site of the factor.

Animals↗

Well-maintained reflex responses of sympathetic nerve activity to stimulation of baroreceptor, chemoreceptor and cutaneous mechanoreceptors in neonatal capsaicin-treated rats.

Neonatal treatment with capsaicin (CAP) reduced the content of substance P-like immunoreactivity in the area of the nucleus tractus solitarii and the dorsal horn of the spinal cord in rats. The resting values of the mean arterial blood pressure and heart rate of CAP-treated rats were not significantly different from those of control rats. Reflex responses of the renal sympathetic nerve activity to stimulation of baroreceptor, chemoreceptor and cutaneous mechanoreceptor were compared in CAP- and vehicle-treated rats. Under these conditions the reflex responses were quite well maintained in CAP-treated rats.

Animals↗

Antitumor activity of regional lymph node lymphocytes in patients with lung cancer.

Cytotoxic activities of regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL) of 49 primary lung cancer patients who were subjected to surgical resection were examined by 4 h 51Cr release assay. PBL showed significantly lower cytotoxicity against autologous tumor cells than against K562 and QG-56. On the other hand, RLNL exhibited the same level of cytotoxicity against autologous tumor cells as PBL, although the cytotoxicities against K562 and QG-56 were low. Cytotoxicity of RLNL against autologous tumor cells exhibited a significant degree of depression with the advance of stage, T and N factors. Cytotoxicity of PBL did not significantly change as the stage progressed. When both PBL and RLNL were cultured with purified interleukin-2 (p-IL2) in vitro, their cytotoxic activities were markedly augmented and the cytotoxicities could not be diminished by the treatment with anti-Leu-7 + anti-Leu-11b + C'. These facts indicate that the augmented cytotoxicity may be due to lymphokine activated killer (LAK) cells.

Cytotoxicity, Immunologic↗

Role of tumor-infiltrating lymphocytes in the host defense mechanism against lung cancer.

Tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) were recovered from 22 patients with primary lung cancer. The TIL did not exhibit any cytolytic activity against various target cells. The average percentage of TIL recovered was 6.7 +/- 1.3% in patients without recurrence, as compared to 3.6 +/- 0.6% in those with recurrence within 2 years after complete resection of lung cancer (P less than 0.05). The average cytostatic activity of TAM was 38.5 +/- 6.8% in patients without recurrence, although it was 25.2 +/- 4.6% in those with recurrence within 2 years after complete resection (P less than 0.1). The activity of macrophage activating factor (MAF) induced by TIL was also higher in patients showing no recurrence. A significant positive correlation was observed between MAF activity induced by TIL and the cytostatic activity of individual TAM. These results suggest that antitumor activity of TAM may be controlled by specifically sensitized TIL through lymphokines.

Adenocarcinoma↗

Immunohistological characterization of human monoclonal antibody against lung cancer.

Using immunoperoxidase staining method, a human monoclonal antibody (MAb), termed HB4C5, which was generated by fusion of NAT-30 cells with regional lymph node lymphocytes from a lung cancer patient, was examined for tumor specificity. The determinant recognized by HB4C5 MAb was well preserved in usual formalin-fixed paraffin-embedded tissue sections. Experiments with four major histological types of the lung cancer showed that HB4C5 MAb reacted with adenocarcinoma (19/27), squamous cell carcinoma (2/15), and large cell carcinoma (4/6), but not with small cell carcinoma (0/7). The immunoreaction was seen in the cytoplasm. In addition, this MAb also reacted with some gastric and colon adenocarcinomas. Further study on normal lung and nonpulmonary tissues revealed that HB4C5 MAb bound only type II pneumocytes and proximal tubules of normal kidney.

Adenocarcinoma↗

Results of surgical treatment of patients with T3 non-small cell lung cancer.

Sixty-one patients with T3 non-small cell lung cancer were surgically treated in our department from February, 1974, through April, 1986. The overall 5-year survival, excluding patients with pleurisy, was 23%, and the 5-year survival for patients undergoing complete resection and incomplete resection was 42% and 10%, respectively (p less than 0.01). Survival in patients with T3 N0 and T3 N1 or N2 disease was 33% and 0 at 5 years, respectively. The prognosis for patients with pleurisy was poor, and all died within 3 years. Therefore, complete lung resection should be done in patients with T3 N0 non-small cell lung cancer if complete resection is expected. Long-term survival is less likely for patients with lymph node metastases if complete resection cannot be performed.

Adult↗

Antitumor activity of pleural cavity macrophages and its regulation by pleural cavity lymphocytes in patients with lung cancer.

Antitumor activities of pleural cavity macrophages (PCM) and pleural cavity lymphocytes (PCL) in lung cancer patients were examined. The effect of coculture supernatants of PCL and autologous tumor cells on the cytostatic activity of macrophages was also examined. Cytostatic activity of PCM was not affected by an advance of metastasis to regional lymph nodes or increase of tumor size and difference of histological type. However, the cytostatic activity of PCM was markedly augmented when pleural invasion was limited to within the visceral pleura although it was low when pleural invasion was absent or extended beyond the visceral pleura. On the other hand, PCL did not exert any cytolytic activity against various tumor target cells. However, coculture supernatants of PCL and autologous tumor cells exhibited the activity of macrophage-activating factor against guinea pig peritoneal macrophages. Furthermore, the higher the cytostatic activity of PCM, the higher the macrophage-activating factor activity of the coculture supernatant of PCL and autologous tumor cells was. These results suggested that antitumor activity of PCM was controlled by specifically sensitized PCL through lymphokines.

Animals↗

Evidence that neurokinin A (substance K) neurons project from the striatum to the substantia nigra in rats.

The striatonigral neurokinin A (NKA) pathway in rats was examined with an antiserum specific to the N-terminal region of NKA. Thermal lesions of the striatum decreased both substance P-like immunoreactivity (SP-LI) and NKA-like immunoreactivity (NKA-LI) in the substantia nigra (SN). The releases of SP-LI and NKA-LI in the SN were measured by a push pull superfusion technique. Addition of 50 mM K+ to the superfusion medium increased the releases of both SP-LI and NKA-LI to 1.5-2.0 times the basal values. These results suggest that NKA neurons as well as SP neurons in the striatum project to the SN in rats.

Animals↗

Induction of lymphokine-activated killer cells by intrapleural instillations of recombinant interleukin-2 in patients with malignant pleurisy due to lung cancer.

Intrapleural instillations of recombinant interleukin 2 (RIL-2) were performed in 11 patients with malignant pleurisy due to lung cancer. Kinetic studies on RIL-2 concentration in the pleural effusion and serum revealed relatively long-term maintenance of detectable levels of RIL-2 (over 24 h in the pleural effusion and over 8 h in the serum). Clinically, pleural effusions and cancer cells in the effusions disappeared in 9 of the 11 patients 4 to 10 days after the start of the treatment. Lymphokine-activated killer cells were induced in the effusions of responders who exhibited the disappearance of pleural effusion and cancer cells from the effusion, but not in those of the nonresponders. This induction of lymphokine-activated killer cells may result in the disappearance of cancer cells and pleural effusions. Cytological examination of pleural effusions revealed increases of lymphoblasts, immunoblastic large lymphocytes, and eosinophiles in number and proportion in the responder, although such a phenomenon could not be observed in the nonresponders. Main and frequent side effects of intrapleural instillations of RIL-2 were fever up to 39 degrees C, transient increase of pleural effusion, and eosinophilia. No serious side effect was encountered in our experience.

Adult↗

Distribution of substance K (neurokinin A) in the brain and peripheral tissues of rats.

The regional distribution of substance P (SP) and substance K (SK) in the central nervous system and peripheral tissues of rats was studied. High levels of SK-like immunoreactivity (SK-LI) and of SP-like immunoreactivity (SP-LI) were found in the substantia nigra, nucleus tractus solitarius and nucleus habenula. Neonatal treatment of rats with capsaicin caused a significant decrease in the SK-LI content in the submaxillary gland, but capsaicin had no effect on SK-LI content in any area of the brain. These observations suggest that SK in the brain and peripheral tissues may have significant physiological roles.

Animals↗

Role of tumor-associated macrophages in lung cancer.

The percentage of tumor-associated macrophages recovered (TAMR) and antitumoral activity of tumor-associated macrophages (TAM) were examined in 77 patients with resectable primary lung cancer. TAM was obtained by plastic adherence following trypsinization. TAMR increased from Stage I to Stage II and decreased in Stage III. It also increased in N1 as compared with N0 and N2 but was unrelated to tumor size. However, the cytostatic activity of TAM declined with advance in stage of the disease and an increase of tumor size, but it was relatively unaffected by the presence of metastasis to regional lymph nodes. There was no correlation between TAMR and the recurrence rate; however, cytostatic activity of TAM was correlated significantly with the prognosis of totally resected cases. TAMR and cytostatic activity of TAM tended to be lower in palliatively resected cases. These results suggest that the assessment of the antitumor activity of TAM, but not merely TAMR, may give prognostic information for lung cancer patients.

Adenocarcinoma↗

Establishment and characterization of high- and low-metastatic clones derived from a methylcholanthrene-induced rat fibrosarcoma.

High- (Cl-33H) and low- (Cl-35L) metastatic clones were established from a methylcholanthrene-induced rat fibrosarcoma (FMQ-100). The modal chromosome numbers of the two clones were different. These clones grew in in vitro culture, showing similar growth rate and saturation density. However, in in vivo experiments, Cl-33H exhibited a higher tumor growth rate, tumorigenicity, spontaneous metastatic potential, and experimental metastatic potential than did Cl-35L. Alveolar macrophages obtained from normal syngeneic rats stimulated growth of these clones in vitro, as assessed by [3H]thymidine uptake. Moreover, this effect was greater on Cl-33H than Cl-35L. The growth-promoting effect of macrophages was also observed under the in vitro condition of lack of direct contact between macrophages and tumor cells. These results suggested the possibility that alveolar macrophage-derived growth-promoting factors play some role in the development of pulmonary metastasis in this tumor system, and the difference of susceptibility to the growth-promoting factors might be one of the causes of the different metastatic potentials of Cl-33H and Cl-35L.

Animals↗