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Biomedical subjects

A Noguchi

Publications and source records attributed to A Noguchi.

At least 73 records · Page 4Linked to original sources
PubMed1993

Follow-up study of patients treated with monoclonal antibody-drug conjugate: report of 77 cases with colorectal cancer.

A total of 77 patients with advanced colorectal cancer, including postoperative patients with liver, lung and peritoneal metastases, were treated with single or multiple injections of monoclonal antibody A7-neocarzinostatin (A7-NCS). A follow-up study of the patients treated with A7-NCS was done and the clinical outcome was compared with that of patients given other chemotherapies. In the postoperative patients with liver metastasis, the A7-NCS treatment prolonged survival time when compared with systemic administration of anticancer drugs, while it showed a similar survival time to chemoembolization using multiple anticancer agents suspended in a lipid contrast medium. Among the patients who underwent surgical resection of primary cancer, with or without liver metastasis, there was no difference in overall 5-year survival rate between the group treated with A7-NCS and the group treated with the other chemotherapies. However, the survival time of the patients treated with A7-NCS was longer than that of the patients treated with the other chemotherapies. In addition, the patients given a higher dose of A7-NCS had a longer survival time than the patients given a lower dose of A7-NCS. Human anti-mouse antibody was detected in all the A7-NCS-treated patients examined. There were no serious side effects in any of the patients given A7-NCS. Thus, this study indicates that the A7-NCS treatment is safe and useful for colorectal cancer patients, though some problems remain, such as optimization of injection dose, route, interval, etc., and overcoming human anti-mouse antibody development.

Adult↗
PubMed1993

A new drug delivery system (DDS) development using plasma-irradiated pharmaceutical aids. IV. Controlled release of theophylline from plasma-irradiated double-compressed tablet composed of polycarbonate as a single wall material.

A controlled-release tablet can be obtained by oxygen plasma irradiation on the outer layer double-compressed tablets prepared from theophylline as a core material and polycarbonate derived from bisphenol A (PC) as a single wall material, making this possible that PC is of intramolecular bifunctionality, crosslinkable phenyl group and degradable carbonate group as an effect of plasma irradiation. It was shown that the dissolution profiles can be varied so as to cause release of theophylline at different rates, depending on the set of conditions chosen for tablet manufacturing as well as plasma operational conditions.

Drug Compounding↗
PubMed1993

Enhanced lymphatic delivery of monoclonal antibody following OK432 pretreatment.

The effect of OK432 on the lymphatic delivery of monoclonal antibody (Mab) was investigated by injecting [125I]-Mab A7 into BALB/c mice pre-treated with OK432, and measuring the radioactivity in the regional lymph nodes. The [125I]-Mab A7, when administered subcutaneously to the foot pad, preferentially accumulated in the ipsilateral popliteal and para-aortic lymph nodes. Treatment with OK432 prior to antibody injection significantly enhanced the accumulation of Mab A7 in these regional lymph nodes. These findings suggest that pretreatment with OK432 may constitute a promising method of enhancing the lymphatic delivery of Mab, and improving the efficacy of therapy directed against lymphatic malignancies.

Animals↗
PubMed1993

[Survey for primary tumor site in patients with initial clinical presentation of bone metastasis].

Among the patients who were examined with bone scintigraphy between April 1985 and March 1991, there were 27 patients whose initial clinical manifestation was bone metastasis and who were surveyed for the primary tumor site. The primary tumor site could be identified in 20 patients (74%), consisting of 9 patients with lung cancer, 3 with prostate cancer, 3 with hepatoma, 2 with renal cancer, and one each with thyroid cancer, adrenal cancer, and pleural malignant mesothelioma. In 17 of the 20 patients, the primary site had been detected within two months after presentation. Examinations which were helpful in identifying the primary site included chest radiography, sputum cytology, abdominal sonography, serum prostatic acid phosphatase level and pathologic examination of biopsy specimens. 99mTc-PMT scintigraphy was useful in the diagnosis of the hepatoma when accumulation was observed at the metastatic sites. In 2 patients, lung cancer had been recognized using follow-up chest radiography 3 and 6 months after presentation, respectively. One patient was diagnosed at autopsy as having adrenal cancer. In 7 patients the primary site remains unknown. Histology examination of the biopsy specimen performed in 6 of these patients revealed 4 to be adenocarcinoma and 2 undifferentiated carcinoma. The average survival period of the 17 patients who died was 9.5 months. Four patients are alive, and the outcome in the remaining 6 could not be determined.

Adult↗
PubMed1993

[A new application of immunoconjugate to reduce the local recurrence of colorectal cancer].

To examine whether or not immunoconjugate-A7-NCS can contribute for the reduction of local recurrence of colorectal cancer, the present study was undertaken. The study included examination of local retension, lymphatic delivery and inhibitory effect on tumor development after local administration of A7-NCS. The result showed that locally injected A7-NCS showed a high local retension, a high regional lymph node accumulation and a high inhibitory effect on tumor development. This finding indicates that A7-NCS can be a new promising tool for reducing the local recurrence of colorectal cancer.

Animals↗
PubMed1992

Local administration of monoclonal antibody-drug conjugate: a new strategy to reduce the local recurrence of colorectal cancer.

This report investigates the application of monoclonal antibody A7 and its drug conjugate in locally controlling colorectal cancer. The experimental protocol consisted of local retention, lymphatic delivery, normal organ distribution, systemic toxicity, and tumoricidal effects. When 125I-labeled monoclonal antibody (Mab) A7 was injected into the pelvis and the thigh of Balb/c mice, a high local retention unrelated to antigen-antibody interaction was observed at the injected site for 24 h after injection. An analysis of local retension properties related to antigen-antibody interaction, conducted by intratumorally or peritumorally injecting 125I-Mab A7 into the tumor-bearing athymic nude mice, revealed a significantly higher tumor localization of Mab A7 in comparison to i.v. injection. 125I-Mab A7 accumulated to a great extent in the ipsilateral regional lymph node but not in the contralateral regional lymph node. Normal organ accumulation of Mab A7 was lower in the locally injected group than in the i.v. injected group. Intratumoral injection of Mab A7-neocarzinostatin (A7-NCS) led to the complete remission of established tumor in 5 of 6 antigen-positive xenograft-bearing mice but exhibited a complete remission in only 1 of 6 antigen-negative xenograft-bearing mice. A single local injection of A7-NCS inhibited tumor development in 12 of 16 and 5 of 15 antigen-positive tumor-bearing mice and antigen-negative tumor-bearing mice, respectively, whereas neither a systemic injection of A7-NCS and NCS nor a local injection of NCS and saline had a notable inhibitory effect on tumor development. Systemic toxicity of NCS was markedly reduced when it was locally administered in the antibody-conjugated form. These findings indicate that local injection of immunoconjugate is a promising new field for controlling the local recurrence of colorectal cancer.

Animals↗
PubMed1992

Sexual transmission of hepatitis C virus among female prostitutes and patients with sexually transmitted diseases in Fukuoka, Kyushu, Japan.

The authors investigated the prevalence of antibody to hepatitis C virus (anti-HCV) in 404 female prostitutes, 428 clinic patients with a history of at least one episode of sexually transmitted disease, and 8,944 blood donors who served as the controls. All subjects were Japanese, and all studies were carried out in Fukuoka, Kyushu, Japan, in 1989. The prevalence of anti-HCV was significantly higher in the prostitutes (6.2%), in the female patients with sexually transmitted diseases (6.1%), and in the male patients with sexually transmitted diseases (2.9%) than in the controls (1.5%). Prevalence of anti-HCV increased with age in prostitutes and in the controls. The prevalence of anti-HCV in those who had been involved in prostitution for 1 year or more (8.1%) was higher than in those who had been involved in prostitution for less than 1 year (1.4%), but the difference was not statistically significant. One of the 152 anti-HCV negative prostitutes seroconverted between 1 and 2 years later. Among the subjects with sexually transmitted diseases, patients with a history of at least one episode of syphilis had a significantly higher prevalence of anti-HCV (4.4%) than the controls. Patients with acute urethritis and cervicitis also showed a high prevalence of anti-HCV (3.6% and 6.7%, respectively). These data support the possibility of sexual transmission of hepatitis C virus.

Adolescent↗
PubMed1992

Prophylaxis with carbon-adsorbed mitomycin against peritoneal recurrence of gastric cancer.

Attempts to prevent peritoneal carcinomatosis after surgery for gastric cancer by intraperitoneal administration of anticancer drugs have not been successful, largely because the drugs are not retained in the peritoneal cavity. We have assessed the prophylactic efficacy of a delayed-release preparation--mitomycin adsorbed onto activated charcoal (M-CH). 50 patients with gastric cancer and serosal infiltration were randomly assigned intraperitoneal treatment with M-CH (50 mg mitomycin intraoperatively) or no anticancer prophylaxis (control). Survival rates for the 3 years of follow-up were significantly higher among the 24 M-CH recipients (1 was lost to follow-up) than among the 25 controls (p less than 0.01). There were significant differences in survival between the groups at 1.5 years after randomisation (difference 34.6% [95% confidence interval 8.5-60.8%]; p less than 0.01) and at 2.0, 2.5, and 3.0 years (41.7% [14.2-69.1%]; p less than 0.005). The concentration of mitomycin was significantly higher in peritoneal exudate than in plasma for 24 h after drug administration. Side-effects were slight and well tolerated. Thus, peroperative intraperitoneal treatment with M-CH seems to improve survival after gastrectomy for gastric cancer, presumably by a prophylactic effect on peritoneal recurrence.

Adsorption↗
PubMed1992

Hepatitis C virus detection is facilitated by the combined use of c100 protein and GOR epitope.

Assay for the antibody to the c100 protein (anti-c100) lacks sensitivity in terms of detection of hepatitis C virus (HCV) in all samples. The author used anti-c100 and antibody to the GOR epitope (anti-GOR) by the enzyme-linked immunosorbent assay to examine 524 patients with chronic liver disease and 682 volunteer blood donors in Fukuoka, Japan. The prevalence of HCV infection, as revealed by the presence of anti-c100 and/or anti-GOR, was 3.9% in 540 volunteer blood donors, 12.7% in 142 volunteers with abnormal liver function, 7.4% in 135 patients with HBsAg-positive liver disease and 89.5% in 389 patients with non-A, non-B (NANB) liver disease. These results show a higher prevalence than demonstrated only by the anti-c100 in NANB liver disease patients (82.5%, P < 0.01). The concurrence of anti-c100 and anti-GOR in subjects with HCV infection was 23.8% in 21 volunteer blood donors, 44.4% in 18 volunteers with abnormal liver function and 61.2% in 348 NANB liver disease patients. The concurrence seems to increase with deterioration of liver function. We concluded that combination assay for anti-c100 and anti-GOR demonstrated a more accurate prevalence of HCV infection than single assay for anti-c100 among NANB liver disease patients, and that the presence of anti-GOR plays a role in liver disease in anti-HCV-positive subjects.

Adolescent↗
PubMed1992

The effects of breastfeeding and presence of antibody to p40tax protein of human T cell lymphotropic virus type-I on mother to child transmission.

We examined the effects of various factors, including duration of breastfeeding, the status of mother's anti-p40tax, and titre of mother's anti-human T cell lymphototropic virus type-I (HTLV-I) on mother to child transmission of HTLV-I in 76 HTLV-I carrier mothers and 175 of their children. The overall prevalence of anti-HTLV-I among children was 16.0%. The prevalence of anti-HTLV-I among children breastfed for over 3 months was significantly higher (27.6%) than that of those breastfed for under 3 months (5.1%; P = 0.012). Of the 78 bottle-fed children, 10 (12.8%) were positive for anti-HTLV-I. In the children breastfed for over 3 months, the prevalence of anti-HTLV-I among 37 children of anti-p40tax positive mothers was 37.8% and that of 21 children of anti-p40tax negative mothers was 9.5%, a significant difference (P = 0.044). These data suggest that about 13% of bottle-fed children born to carrier mothers are infected with HTLV-I by routes other than breast milk, and that the mother's anti-p40tax can serve as a marker of infectivity of HTLV-I in the case of breastfeeding for over 3 months.

Adolescent↗
PubMed1992

Enhanced tumor localization of monoclonal antibody by treatment with kininase II inhibitor and angiotensin II.

The effect of kininase II inhibitor, enalapril, on the delivery of monoclonal antibody A7 to the targeted tumor was investigated using athymic mice bearing human colon cancer, SW1116. Enalapril alone, which enhances tumor vascular permeability through the kinin-generating cascade, did not increase the uptake of 125I-labeled A7 (125I-A7) in SW1116 due to the systemic hypotension induced by its inhibitory effect on angiotensin converting enzyme. However, with combined angiotensin II (AT-II) and enalapril treatment, a 2-fold increase in the accumulation of 125I-A7 was seen when compared to A7 alone. This marked increase was presumably due to increased tumor vascular permeability induced by enalapril combined with the absence of hypotension due to the actions of AT-II. This approach might be useful in radioimmunodetection and immunotargeting chemotherapy using monoclonal antibody.

Angiotensin II↗
PubMed1992

Efficacy and specificity of a monoclonal antibody-drug conjugate in chemotherapy by intratumoral injection.

The murine monoclonal antibody (Mab) A7 conjugated to neocarzinostatin (A7-NCS) was injected intratumorally (IT) into tumor bearing nude mice. Its pharmacokinetics and tumoricidal effects were compared in the high, moderate and low antigen expressing xenograft for SW1116, WiDr and KB tumor-bearing nude mice, respectively. When injected IT into nude mice, [125I]A7-NCS was retained in the tumors according to the degree of antigen expression; it was also disseminated into the blood inverse proportion to the antigen expression. Addition of an excess amount of Mab A7 reduced [125I]-A7-NCS accumulation in SW1116 xenograft and elevated the [125I]A7-NCS concentration in the circulation. Complete tumor reduction was found in all 5 mice with SW1116 tumor, and 2 of 5 mice with WiDr tumor. However, only incomplete tumor suppression was observed in mice with the KB tumor. The significant tumor reduction in SW1116 bearing nude mice was attenuated when excess of Mab A7 was simultaneously administered with A7-NCS. These findings indicate that A7-NCS was localized in the target tumors and exerted its tumoricidal effects depending on the degree of antigen-antibody interaction when administered IT. Thus, A7-NCS can be used successfully in vivo for local therapy, auguring new and promising applications for local cancer therapy.

Animals↗
PubMed1992

[Evaluation of micro particle enzyme immunoassay (MEIA) for the demonstration of antibody to hepatitis B surface antigen].

A fully automated microparticle enzyme immunoassay (IMx AUSAB, Abbott) has been recently introduced for the detection of the presence of antibody to hepatitis B surface antigen (anti-HBs). The present trial was carried out to determine the feasibility of using the IMx AUSAB with sera and plasma, and for comparison with RIA (AUSAB, Abbott) and EIA (AUSAB EIA, Abbott). According to the kinds of vaccines used and locations of residents, the subjects were divided into six groups. Results obtained were as follows; In the test of 642 sera from 446 vaccines and 196 other inhabitants of Okinawa and Miyazaki prefectures, 388 (87.0%) were found positive for anti-HBs using IMx, 392 (87.9%) with RIA and 359 (80.5%) with EIA. Among those vaccinated with recombinant vaccines, 96.6% were found positive with IMx, 96.2% with RIA and 89.4% with EIA. Among subject vaccinated with plasma derived vaccines, 72.9% were found positive with IMx, 75.7% with RIA, and 68.5% EIA. Quantitative agreement between IMx and RIA among the six groups gave linear correlation coefficients ranging from 0.459 to 0.821. In the group vaccinated with the recombinant vaccine by K company (r = 0.459), anti-HBs was confirmed in many sera by IMx compared to that confirmed by RIA and EIA. In addition, anti-HBs was assayed within one hour by IMx and the procedure was simplified by autoanalyser equipped for this method. The results indicate that the sensitivity of IMx is equal to that of RIA and more than that of EIA, and that quantitative linear correlations were obtained between IMx and RIA, and IMx and EIA.

Hepatitis B Antibodies↗
PubMed1992

[Evaluation of micro particle enzyme immunoassay technique (MEIA)-IMx for the detection of antibody to hepatitis A virus].

A new micro particle enzyme immunoassay technique (MEIA, IMx HAVAB, Abbott) has been recently introduced for the detection of antibody to hepatitis A virus (anti-HA). To evaluate the feasibility of the IMx HAVAB, we carried out comparison tests between MEIA, RIA and EIA. Furthermore, we investigated the prevalence of anti-HA in Fukuoka City and Yonaguni Island, Okinawa, Japan using this method. Results obtained were as follows: In the test of 514 sera, 254 (49.0%) were positive by the three methods, and the remaining 260 (50.6%) were negative by the three methods. Examination of diluted sera using IMx revealed that IMx can be used as efficiently as RIA and EIA. Quantitative linear correlations were found between IMx and RIA (r = 0.973), and IMx and EIA (r = 0.969). Anti-HA was assayed within 45 minutes by IMx, and the procedure was simple because of the auto analyser used in this method. On Yonaguni Island, a significant decrease in the overall prevalence of anti-HA from 75.2% in 1980 to 61.1%, in 1990 (p less than 0.05) was found, the prevalence of anti-HA on Yonaguni Island in 1990 was significantly higher than in Fukuoka City (p less than 0.001). These results indicate that the sensitivity of IMx is equivalent to those of RIA and EIA, that it is easier to use than either RIA or EIA and that hepatitis A virus infection in Okinawa, has significantly decreased during the past 10 years, but is still significantly more frequent than in Fukuoka City.

Adolescent↗
PubMed1992

Tropoelastin gene expression in the rat pulmonary vasculature: a developmental study.

The elastic laminae in a vessel provide resilience to its wall. In perinatal and adult rats, we used in situ hybridization to localize the mRNA for tropoelastin (TE) in endothelial cells, medial smooth muscle cells, and adventitial fibroblasts of pulmonary arteries and veins to determine the contribution of these cells to laminae formation. We found that 1) all three cell types are elastogenic but for each the ontogenic pattern is different, 2) signal in the artery is strongest in the late fetal lung, 3) postnatally TE expression decreases first in the outer medial smooth muscle cells, and 4) the pattern of expression in arteries differs from that in veins. In the d 19 fetus, the signal for TE mRNA was higher in arteries than in veins. In the immediate postnatal period, the arterial signal declined, whereas the signal in veins increased. By postnatal d 21, the arterial TE signal per cell had significantly decreased to an intensity lower than that in veins. In the adult rat lung, no TE mRNA was detected by in situ hybridization. The reciprocal alterations in TE expression in pulmonary arteries and veins may suggest a response to the postnatal change in pulmonary blood pressure. We speculate that because all three cell types are potentially elastogenic they may all play a role in the remodeling that occurs after vascular injury.

Animals↗
PubMed1992

Monoclonal antibody-drug conjugate therapy for the patients with colorectal cancer.

Monoclonal antibody drug conjugate A7 was prepared from a mouse splenocyte immunized against human colon cancer. A7 reacted with 80 percent of colorectal cancer and pancreatic cancer. A7 was bound covalently to neocarzinostatin (NCS) to form A7-NCS. A7-NCS had strong cytotoxic activity in vivo and in vitro study. A total of 77 patients with colorectal cancer, including the patients with liver, lung and peritoneal metastasis, were treated with A7-NCS. There were some tumor reduction of liver metastasis on CT scan and pain relief. Follow up study of colorectal cancer patients treated with monoclonal antibody drug conjugate A7-NCS was carried out, with comparing to those treated conventional chemotherapy. Survival rate of the patients with postoperative liver metastasis treated with A7-NCS was slightly higher than that of the patients treated with conventional intraarterial infusion chemotherapy. There was no difference between the group treated with A7-NCS and that treated with conventional chemotherapy in the overall postoperative survival. Patients given a higher dose of the conjugate had a higher survival rate. There were no serious adverse effects in the patients given A7-NCS. Human anti-mouse antibody (HAMA) was detected in all A7-NCS treated patients.

Antibodies, Monoclonal↗
PubMed1992

Effects of casein and soy-protein on alpha-linolenic acid metabolism in rats.

In order to study the effects of different proteins on alpha-linolenic acid (alpha-LnA) metabolism, rats were given the diet added respectively with milk casein and soy-protein isolate (SPI) as sources of proteins and perilla oil as a source of lipid. The results obtained are as follows. The ratio of (C20:3 + C20:4)/C18:2 in liver microsomal PL, liver PE fraction, and kidney PE and PC fractions was significantly lowered by the SPI treatment when compared to the casein treatment, similarly to the already established results. In the liver microsomal PL and PE and PC fractions of liver and kidney in rats treated with SPI, there was also observed a significant decrease or a decrease tendency in the (C20:4 + C20:5)/C18:3 ratio. A similar tendency was again shown in the sigma (n-3)M/C18:3 ratio indicating metabolic conversion from C18:3(n-3) to C22:6. On the other hand, contrary to the ratios of (C20:3 + C20:4)/C18:2, sigma (n-3)M/C18:3, and (C20:3 + C20:5)/C18:3, the (C22:5 + C22:6)/C20:5 ratio which is the parameter for metabolic conversion of C20:5(n-3) was elevated in the PE and PC fraction of liver, heart and kidney in the SPI group compared to the casein group. Then, further analysis of the metabolic process from C20:5 to C22:6 showed that the C22:5/C20:5 ratio increased while the C22:6/C22:5 ratio decreased in the SPI group compared to the casein group. Based on these results, it is assumed that the metabolic process from C18:3(n-3) to C20:5(n-3) and from C22:5 to C22:6 is affected by SPI but that the elongation process from C20:5(n-3) to C22:5(n-3), on the contrary, is rather accelerated by SPI.

Animals↗