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Biomedical subjects

I Hirai

Publications and source records attributed to I Hirai.

At least 19 recordsLinked to original sources

Localization of pNT22 70 kDa heat shock cognate-like protein in the plasma membrane.

It has been argued that 70 kDa heat shock cognate (hsc73)-like molecules may be expressed on the surface of certain cells, but direct evidence of this has yet to be found. To clarify whether this molecule belongs to hsc73 itself, the membrane protein fraction of Daudi cells was isolated by Triton X-114 phase separation and the reactivity of this membrane protein fraction was assessed with monoclonal antibodies (mAbs) which react with 70 kDa heat shock protein (hsp) family, i.e., NT22, A15 and 3A3. In western blotting analysis, mAb NT22-defined protein (pNT22) was clearly detected as a membrane protein of Daudi cells with an approximate molecular size of 70 kDa, whereas pNT22 was not recognized by anti-cytoplasmic hsc73/hsp72 mAbs A15 or 3A3. By using deleted recombinant hsc73 proteins, it was determined that mAb NT22 recognizes the N-terminal 350-372 amino acid stretches of the hsc73 protein. mAb NT22 also reacted with the cell surface protein of Daudi cells in FACS analysis. Taken together, our present data strongly suggest that pNT22 may be a novel hsc73-like protein that is localized in the plasma membrane.

Antibodies, Monoclonal

[Surgical treatment of lung cancer with chest wall invasion].

From January 1986 to May 1998, 45 lung cancer patients with chest wall invasion (P3) underwent resection (40 male, 5 female), (median age 63.2 yrs (30-79)). Histological types were squamous cell carcinoma in 20, adenocarcinoma in 14, large cell carcinoma in 7, adenosquamous cell carcinoma in 2, and unknown in 2. Operative methods of lung resection were total pneumonectomy in 2, bilobectomy in 3, lobectomy in 38, and partial lung resection in 2. Resection was regarded as complete in 35 and incomplete in 10 patients. Thirty one patients had negative lymph nodes (N0), 9 had peribronchial or hilar lymph node metastases (N1), and 5 had mediastinal lymph node metastases (N2). The extent of tumor invasion to chest wall was P3a (invasion within parietal pleura) in 11, P3b-c (invasion to intercostal muscle) in 16, P3d (invasion to rib) in 18, patients. 5-year survival rate was totally 19.7%. Cisplatin based chemotherapy and concurrent thoracic radiation following surgery (CCRT) was performed in latest nine P3d cases. Partial response was observed in 5 of 9 cases (response rate 56%) and viable tumor cell in the primary site was not seen histologically in 5 of 9 cases. Three year survival rate was 46.9% for CCRT(+) 11.1% for CCRT(-). Acturial 5-year survival rate in P3a-d was 19.76%. P3d cases had poor survival, but CCRT improved prognosis of P3d cases.

Adult

Analysis of the early postoperative serum carcinoembryonic antigen time-course as a prognostic tool for bronchogenic carcinoma.

BACKGROUND: The serum kinetics of carcinoembryonic antigen (CEA) after resection of lung carcinoma are not well characterized. Its prognostic implications remain unclear. This study was designed to clarify the correlation between postoperative CEA time-course and patient prognosis. METHODS: The authors analyzed early postoperative CEA time-course in 31 lung carcinoma patients using nonlinear least square analysis with the following three equations: Equation 1: C(t) = C(0); Equation 2: C(t) = C(0)exp(-kt); and Equation 3: C(t) (C(0)PLAT)exp(-kt) + PLAT, in which t: postoperative day; C(t): postoperative CEA; PLAT: postoperative CEA at plateau; C(0): CEA at postoperative Day zero; and k: rate constant of elimination. The equation that yielded the least Akaike's information criterion was adopted as the best fitting regression equation for each patient. When Equation 3 was adopted, postoperative CEA production (PROD) was calculated as PLAT multiplied by k. RESULTS: Equations 1, 2, and 3 were adopted for 16 (Group 1), 0, and 15 (Group 2) patients, respectively. In Group 1, no decrease in serum CEA level after surgery was detected and CEA production appears to have been little or none. In Group 2, biologic CEA half-life was 1.1 +/- 0.7 days and was not useful for predicting patient prognosis. Tumor recurrences were observed in 9 of the Group 2 patients 19 +/- 9 months postoperatively and there was no significant difference in PLAT or PROD between patients with and without recurrence. Early recurrence within 6 months after surgery was recognized in 5 (early-REC) of the 15 Group 2 patients, in whom there was a tendency for PLAT to be higher than in the other 10 patients without recurrence (early-NON) (early-REC: 3.8 +/- 4.9 ng/mL; early-NON: 1.5 +/- 1.1 ng/mL; P = 0.08). PROD was significantly higher in early-REC than in early-NON (early-REC: 3.5 +/- 4.2 ng/mL/day; early-NON: 0.8 +/- 0.4 ng/mL/day; P < 0.05). CONCLUSIONS: Although PROD is more sensitive than PLAT, both parameters appear to be useful as prognostic tools for predicting early recurrence after resection of lung carcinoma. This is probably because they represent the number of residual tumor cells immediately after surgery.

Adult

Preferential binding with Escherichia coli hsp60 of antibodies prevalent in sera from patients with rheumatoid arthritis.

One hundred thirty-two patients with various connective tissue disorders, including 60 with rheumatoid arthritis (RA), had antibodies against human as well as Escherichia coli hsp60 in titers significantly higher than those of normal controls. There was a correlation between titers of antibody to human hsp60 and those to E. coli hsp60. Levels of antibodies against human and E. coli hsp60 were lower in joint fluids than in sera, indicating little production of antibodies in the joint. Antibodies affinity-purified with E. coli hsp60 bound strongly with the homologous hsp60, but weakly with human hsp60. However, antibodies affinity-purified with human hsp60 bound comparably with both E. coli hsp60 and human hsp60. Antibodies affinity-purified with Mycobacterium tuberculosis hsp65 bound to human hsp60 with a reactivity similar to the reactivity of those affinity-purified with human hsp60. The reactivity to the three hsp60 species was lost when sera were absorbed with E. coli hsp60, while the reactivity to E. coli hsp60 remained after extensive absorption with M. tuberculosis hsp65 or human hsp60. These results indicate that anti-hsp60 antibodies in patients with RA and other connective tissue disorders are raised by infection with intestinal microorganisms such as E. coli. They may represent another example of autoimmune responses triggered by antigenic mimicry of host proteins to microbes and suggest that the reactivity of antibodies from RA patients with M. tuberculosis hsp65 might have been a cross-reaction with the E. coli homologue.

Antibodies

The novel compound NO-1886 activates lipoprotein lipase in primary cultured adipose and skeletal muscle cells.

As previously reported, we have discovered that a novel compound, NO-1886 (diethyl 4-[(4-bromo-2-cyanophenyl)carbamoyl] benzylphosphonate) has a powerful lipoprotein lipase (LPL) stimulating activity. Oral administration of NO-1886 increased LPL activity in postheparin plasma of experimental animals, resulting in the reduction of plasma triglyceride with concomitant elevation of high density lipoprotein cholesterol. However, the mechanism of NO-1886 on LPL activity is not clearly understood. To address this problem, we examined the effect of NO-1886 on LPL activity in primary rat cell culture isolated from adipose and skeletal muscle tissue. NO-1886 increased total LPL activity 18% and 23% in adipocytes at a dose of 3 and 10 micrograms/ml, respectively, and 43% at a dose of 10 micrograms/ml in skeletal muscle cells. These results indicate that NO-1886 may act directly on LPL-producing cells such as adipose and skeletal muscle.

Adipose Tissue

[Induction chemotherapy based on histoculture drug response assay for a patient with advanced thymic cancer--a case report].

Histoculture drug response assay (HDRA) was applied to a biopsy specimen of advanced thymic cancer from a 68 years-old male patient. HDRA revealed that the tumor was not sensitive to CDDP but highly sensitive to 5-FU, ADM and MMC, which were administered as induction chemotherapy. The tumor regressed to 14% of the pretreatment size and was able to be completely resected with right and left brachiocephalic veins, superior vena cava, pericardium, right phrenic nerve and a part of right lung. Histologically, only a few small cancer nests remained in the fibrous tissue. The patient is alive and disease free 32 months after surgery. This result suggests that HDRA is useful to select anticancer agents which are sensitive to a rare kind of carcinoma such as thymic cancer.

Antineoplastic Combined Chemotherapy Protocols

Involvement of peptide antigens in the cytotoxicity between 70-kDa heat shock cognate protein-like molecule and CD3+, CD4-, CD8-, TCR-alpha beta- killer T cells.

We previously reported that the 70-kDa heat shock cognate protein-like molecule (hsc70) is expressed on the cell surface along with the neoplastic transformation of rat fibroblast and that this molecule is recognized by CD3+, CD4-, CD8-, NKR-P1-, and TCR-alphabeta- T (DNT) killer cells in an MHC class I-unrestricted fashion. We investigated the mechanism of interaction between hsc70 and DNT cells. H-ras oncogene-transformed rat fibrosarcoma W31 cells expressed hsc70 on the cell surface in almost the same density when the cells were growing in a conventional 5% FCS (5% W31) as when the cell growth was inhibited in the cultivation with 1% FCS (1% W31). However, DNT cells lysed only 5% W31, but not 1% W31. Since these observations suggest that certain peptide Ags of the fast growing W31 cells may play a role in the interaction between hsc70 and DNT cells, we pulsed 1% W31 cells with trifluoroacetic acid (TFA)-extracted fast growing W31 tumor Ags of less than 3000 Da in molecular size. We also pulsed 1% W31 with TFA-extracted Ags from moderate growing W14 tumors and whole fetus tissues. Our data indicated that DNT cells were clearly cytotoxic to 1% W31 pulsed only with TFA-extracted Ags from W31 tumors. Anti-rat hsc70 mAb completely blocked this cytotoxicity. In addition, pronase K treatment of Ags clearly inhibited the cytotoxicity by DNT cells. Taken together, these data suggest that the complex of peptide Ag and hsc70 is involved in the cytotoxic mechanism between hsc70 and DNT cells.

Animals

Inhibition of natural killer cell cytotoxicity by cell growth-related molecules.

Certain MHC class I molecules on target cells are known to inhibit the cytotoxic action of NK cells. By using monoclonal antibody (mAb) Cho-1, we have found inhibitory non-MHC class I cell surface molecules that are noncovalently-associated with 200 kDa and 40 kDa antigens. Poly I-C-induced rat NK cells were not cytotoxic to rat fetus-derived fibroblast WFB cell line. In contrast, NK cells were cytotoxic to H-ras oncogene-induced transformants of WFB, W14 and W31. FACS analysis indicated that mAb Cho-1 reacts with WFB, but not with W14 and W31 cells. Thus, this antigen may disappear concomitantly with cell growth and transformation. Cho-1 antigens were also expressed on other NK-resistant lines, such as mouse BALB3T3 fibroblast, EL-4 lymphoma and human fibroblast HEPM. However, they were not expressed on NK-sensitive mouse YAC-1 and H-ras transformant (Brash) of BALB3T3 cells. Furthermore, treatment of target cells with IFN-gamma clearly induced the cell surface expression of Cho-1 antigens, and conferred a resistance to NK cytolysis on target cells. These data strongly suggest that Cho-1 antigen expression may correlate with target cell susceptibility to NK cells. Indeed, treatment of NK-resistant WFB as well as HEPM cells with F(ab')2 fragments of mAb Cho-1 resulted in the acquisition of susceptibility to NK cytolysis. Cho-1 antigens may be novel molecules that regulate the NK resistance of cells.

Animals

Evaluation of effect of lung resection on lobar ventilation and perfusion using intrabronchial capnography.

Intrabronchial capnography was applied in 11 lung cancer patients to investigate the effects of lobectomy on regional lung function. Spirometry and intrabronchial capnography were performed before surgery (PRE), and during the early (POST1,19 +/- 5 POD) and late (POST2, 184 +/- 98 POD) postoperative periods. End-tidal carbon dioxide concentration (EtCO2) and Smidt's velocity profile index (V-index) were calculated from each lobar capnogram obtained bronchoscopically. The V-index of lobes without cancer on the operated-on side increased after surgery (PRE, 10.7 +/- 5.0%; POST1, 14.3 +/- 9.4%, NS; POST2, 16.8 +/- 8.6%, p < 0.05), while the V-index on the unoperated-on side decreased after surgery (PRE, 10.5 +/- 5.3%; POST1, 7.9 +/- 3.5%, p < 0.05; POST2, 7.2 +/- 2.9%, p < 0.05). EtCO2 after surgery was lower on the operated-on side (POST1, 5.1 +/- 1.1%; POST2, 4.6 +/- 1.1%) than on the unoperated-on side (POST1, 5.4 +/- 0.9%, p < 0.05; POST2, 5.0 +/- 0.9%, p < 0.01). Since the V-index and EtCO2 are compatible with the expiratory flow rate and the perfusion/ventilation ratio, respectively, we concluded that the air flow decreased on the operated-on side and increased on the unoperated-on side postoperatively and that perfusion on the operated-on side was more severely reduced than ventilation. These findings suggest that intrabronchial capnography is useful for assessing the ventilation and perfusion of the individual lobes as single units.

Aged

High expression of heat shock protein 60 in follicular cells of Hashimoto's thyroiditis.

Heat shock protein 60 expression in the thyrocytes of Hashimoto's thyroiditis and Graves' disease was studied immunohistochemically. Thyrocytes of Hashimoto's thyroiditis showed high expression of heat shock protein 60 not only in tall eosinophilic-cells but also in low and flattened cells, although the former was stained with moderate to strong staining intensity and the latter weakly to moderately. Follicular cells around lymphoid cell follicles were stained more intensely, whereas cells apart from lymphoid cell follicles were stained weakly to moderately. In Graves' disease, only follicular cells around lymphoid cell follicles were stained with varying intensities. Since the pattern in all positive staining was granular, it was thought that heat shock protein 60 overexpressed in thyrocytes located on mitochondria. To investigate the immunological role of overexpression of self heat shock protein 60 in the thyrocytes of Hashimoto's thyroiditis, gamma delta TCR+ T-cells in the tissue and the IgG class of anti-self heat shock protein 60 antibodies were studied. gamma delta TCR+ T-cells were detected among lymphoid cells scattered in interfollicular connective tissue. No difference in antibody level was seen among subjects with Hashimoto's thyroiditis, Graves' disease and normal subjects. Self heat shock protein 60 overexpression in the thyrocytes of Hashimoto's thyroiditis may play a disease-modifying role, although it does not influence the anti-self heat shock protein 60 antibody level.

Animals

[Double primary lung cancers producing alpha-fetoprotein].

A 81-year-old male with a high serum alpha-fetoprotein (AFP) level of 2644 ng/ml underwent left pneumonectomy for squamous cell carcinoma in the lower lobe and large cell carcinoma in the upper lobe. Both tumors were classified as pathological T2N0M0 and stage I. The AFP level was normalized to be 19 ng/ml in 49th postoperative day. Immunohistochemical staining using anti-AFP antibody demonstrated AFP granules only in the large cell carcinoma. The study of lectin affinity against the serum AFP revealed that the concanavalin A (Con-A) non-reactive fraction rate was 14%, the lentil agglutinin (LCA) non-reactive and strongly reactive subfractions were 16.7 and 83%, respectively and P2, P4 and P5 subfractions of the erythroaggultinating phytohemagglutinin (E-PHA) were 58.6, 24.9 and 16.5%, respectively. According to the analysis of 21 cases reported in the Japanese literature including our case, the AFP did not demonstrate a common affinity pattern against the Con-A but the common pattern resembling hepatocellular carcinoma against LCA and E-PHA.

Aged

[Surgical resection of pulmonary metastases from colorectal cancer].

Fourteen patients with known primary colorectal adenocarcinoma underwent pulmonary resection for its pulmonary metasoasis. The cumurative survival rate at five years was 25.7% in all patients and 37.5% in 9 patients with a solitary metastasis. One of two patients with both pulmonary and hepatic metastases survived 33 months with no evidence of recurrence after pulmonary and hepatic resection. Although none of seven patients with tumor smaller than 3.5 cm in diameter had regional lymph node metastasis, two of three patients with tumors larger than 3.6 cm in diameter had hilar lymph node metastases. Lobectomy and mediastinal lymph node dissection may be recommended for the patient with large tumor.

Adenocarcinoma

[Thoracoscopic partial resection of the lung for peripheral lung tumor].

We report a thoracoscopic partial resection of the lung for the peripheral lung tumor in a 66-year-old woman. Her chest roentgenogram and computed tomographic scan showed a single tumor 1.9 cm in diameter within the periphery of the right lower lobe. A solitary metastatic lung tumor of colon cancer, which was resected one year ago, was suspected. Partial resection of the lung involving this tumor was performed using the MULTIFIRE ENDO GIA 30 disposable surgical stapler under thoracoscopy. There was neither air leak nor bleeding at the resection line. Pathological examination of the tumor revealed benign localized pleural mesothelioma. Her postoperative course was uneventful and she was discharged from the hospital on the eighth postoperative day. Thoracoscopic pulmonary resection using EndoGIA is a safe technique for a peripheral lung tumor.

Aged

[Human growth hormone and prolactin during pregnancy (author's transl)].

In order to know the secretory behaviors of human growth hormone (hGH) and human prolactin (hPRL) during pregnancy, the following studies were undertaken. Twenty three normal pregnant women of every period of gestation, eighteen women of postpartum and five nonpregnant subjects volunteered for this study. After fasting overnight, these volunteers were placed at complete bed rest, and a fasting antecubital venous blood sample was drawn at 8:00 a.m. Then L-arginine, 30 g, was infused intravenously over a 30 minute period, and venous blood samples were drawn at 30, 45, 60, 90, 120, minutes after infusion. Serum hGH level was detected by hGH radioimmunoassay Kit (Dainabot) and serum hPRL concentration was measured by double-antibody radioimmunoassay system (NIH-NIAMDD). In addition, serum hCS level was measured by hCS-Kobe double-antibody radioimmunoassay system in comparison with the secretory behaviors of hGH and hPRL. 1. Serum hGH, hPRL and hCS concentrations during pregnancy. HGH concentration remained almost unchanged through the course of pregnancy, but hPRL and hCS concentrations increased with the programs of pregnancy. 2. Serum hGH and hPRL concentrations in puerperium. HGH level did not change as compared to that of nonpregnant or pregnant women. HPRL concentration maintained high level in 1-3 postpartum weeks. 3. Effect of arginine on the concentrations of serum hGH, hPRL and hCS during pregnancy. The hGH response decreased, but that of hPRL increased along with the progress of pregnancy. During the arginine loading test there was no significant change in hCS concentration. 4. Effect of arginine on the concentrations of serum hGH and hPRL in puerperium. The HGH response was suppressed at the first week of the postpartum. The response of hPRL was lower than that of late pregnancy. To summarize, hGH and hPRL have some similar biological characters, but there was a difference in secretion pattern of the two hormones during pregnancy. Reserve function of hGH secretion was suppressed, but that of hPRL secretion increased along with the progress of pregnancy. And in the third trimester of pregnancy, the difference of the secretory behavior and secretory reserve function between hGH and hPRL was prominent.

Arginine