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Biomedical subjects

A Noguchi

Publications and source records attributed to A Noguchi.

At least 91 records · Page 5Linked to original sources

[Evaluation of 99mTc-PMT delayed imaging in diagnosis of hepatocellular carcinoma].

99mTc-PMT delayed imaging was performed on 199 patients with hepatocellular carcinoma (HCC), and 72 patients with various hepatic diseases, from which HCC should be differentiated. Of the 199 patients with HCC, 128 (64.3%) showed positive results on 99mTc-PMT images. Of these 128, 102 (51.3%) showed increased uptake of radioactivity by the hepatic tumor as compared with the surrounding non-tumorous area of the liver, and 26 (13.1%) showed equal uptake. On the contrary, only 2 (9.1%) of the 22 patients with other malignant hepatic tumors (7 with cholangiocellular carcinoma and 15 with metastatic liver tumors) showed equal uptake of 99mTc-PMT. These findings indicated that 99mTc-PMT delayed imaging was useful for increasing the specificity in diagnosis of HCC. Of the patients with HCC showing increased uptake on 99mTc-PMT images taken 5-hour after the injection of the radioisotope, 26.3%, 69.6%, and 96.0% showed intense 99mTc-PMT uptake by hepatic tumor on 1-hour, 2-hour, and 3-hour images, respectively. These findings indicated that in diagnosing HCC, 5-hour image should be taken only in the patients with a hepatic tumor showing no increased uptake of radioactivity even on 3-hour image. Moreover, the rate of HCC to take up 99mTc-PMT intensely was higher in patients with hepatic tumor showing filling defect on colloid liver image than in those showing no filling defect (p less than 0.001). The points in the assessment of radioactivity uptake by hepatic tumor on 99mTc-PMT delayed image were as follows: Overlapping of radioactivity excreted into the gall bladder or intestine with the radioactivity of the liver tumors, radioactivity retention in the non-neoplastic portion of the liver, and the radioactivity of the dilated intrahepatic bile duct were noted in 6 (2.6%), 15 (6.5%) and 9 (3.9%), respectively, among the 230 patients with focal space occupying lesions. Further, a patient of giant nodular regenerative hyperplasia showed increased uptake of 99mTc-PMT consistent with the hepatic lesion.

Carcinoma, Hepatocellular↗

[Two cases of pulmonary metastasis of colorectal cancer successfully treated with oral 5'-DFUR].

Two patients with pulmonary metastasis of colorectal cancer, who had previously undergone radical resection of primary tumor, were orally administered 5'-DFUR at 1,200 mg per day. Complete responses were obtained in both. The duration of response was 42 and 13 weeks, respectively. Some side effects such as diarrhea and aguesia were found in each patient, but the treatment could be continued after temporary suspension for a while or by decreasing the dosage. We concluded that pulmonary metastasis of colorectal cancer can respond remarkably to oral administration of 5'-DFUR at 1,200 mg per day, if the tumor cells have sensitivity to this drug.

Adenocarcinoma↗

Prevalence of antibody to hepatitis C virus in hemodialysis patients.

The prevalence of hepatitis C virus infection in hemodialysis patients in Japan was examined using sera from 418 patients from six dialysis units in 1989. The authors made use of an enzyme-linked immunosorbent assay (Ortho Diagnostics). Antibody to hepatitis C virus (anti-HCV) was detected in 127 patients (30.4%), the frequency varying from 20.0% to 34.9% in different units. The mean prevalence of anti-HCV was 20 times higher than that in blood donors. Anti-HCV positivity was not associated with antibody to hepatitis B core antigen, which was not a surrogate marker for non-A, non-B hepatitis agents in this study. Another striking finding of this study was that 84.3% of the anti-HCV-positive patients had normal liver function. Anti-HCV positivity correlated positively with the number of blood transfusions and increased with the duration of hemodialysis; however, it was 22.1% even in 113 patients never given blood transfusion. Acquisition of hepatitis C virus by dialysis patients is, therefore, not only through blood transfusions but also because of hepatitis C virus present within the unit itself. Liver dysfunction in the anti-HCV-positive patients was rare.

Adolescent↗

Urinary pepsinogen I as a tumor marker of stomach cancer after total gastrectomy.

The possibility that urinary pepsinogen I is a tumor marker of stomach cancer after total gastrectomy was examined. To decide the cutoff level of urinary pepsinogen I after total gastrectomy, urine samples from 15 patients who had undergone total gastrectomy for stomach cancer in the early or advanced stages and had been free from recurrence for more than 5 years were examined by pepsinogen I-specific radioimmunoassay. The mean concentration of urinary pepsinogen I was 17.5 +/- 7.4 ng/ml and the cutoff level of urinary pepsinogen after total gastrectomy was set at 32 ng/ml (mean + 2 SD). Twenty-two of 74 cases who had undergone total gastrectomy for stomach cancer were regarded as positive. And 20 of these 22 positive cases had definite clinical signs of recurrence of stomach cancer. There were only two false-positive cases. These results suggest that urinary pepsinogen I will be an useful tumor marker in detecting the recurrence of stomach cancer after total gastrectomy.

Adenocarcinoma↗

Chemical engineering of the monoclonal antibody A7 by polyethylene glycol for targeting cancer chemotherapy.

The murine monoclonal antibody A7 (Mab A7) against human colon cancer was chemically modified with methoxypolyethylene glycol (PEG) (Mr 5000). A high substitution of PEG molecules on Mab A7 produced a progressive reduction in antibody-binding activity. The pharmacokinetic and immunological properties of PEG-modified monoclonal antibody A7 (Mab A7) and the PEG-modified F(ab')2 fragment, which retained their antibody-binding activity, were assessed and compared with the parent Mab A7 and the parent F(ab')2 fragment. Blood clearance of PEG-modified antibodies appeared to be diminished by PEG modification and was fitted by a two-compartment model. Low PEG-substituted Mab A7 showed less organ uptake in the liver and spleen and similar uptake in the lung and kidney, compared with the parent Mab A7. PEG-F(ab')2 showed less uptake in the liver and kidney. Both preparations exhibited less tissue:blood ratios in all resected organs as compared with parent antibodies. Tumor localization was enhanced by PEG modification for the F(ab')2 fragment, but not by PEG modification for the whole Mab A7. Multiple i.v. administration of PEG-modified antibody to rabbit did not appear to elicit a measurable immune response to the antibody portion of the conjugate. In conclusion, PEG-modified antibodies are promising reagents as drug carriers to the target tumor.

Animals↗

Long term observation of the effect of intradermal hepatitis B vaccination on mentally retarded patients.

Sixty-two patients of two institutions for mentally retarded patients were immunized intradermally with 4 micrograms doses of plasma-derived hepatitis B vaccine made in Japan, initially at month 0.1 and 6. The three vaccinations induced antibodies in 93.5% (90.9% in those with Down's syndrome (DS), 94.1% in other forms of mental retardation (OMR) of the vaccinees within 9 months after the first injection, and the percentage of geometric mean titers of antibody above 10 mIU/ml was 89.3% (81.8% DS, 84.3% OMR) within 9 months. Within 2 years, the seroconversion rate showed a significantly higher decrease in subjects with DS (54.5%) than in OMR (86.3%), and the percentage of vaccines with above 10 mIU/ml also showed a significantly higher decrease in subjects with DS (36.4%) than in those with OMR (74.5%) (p less than 0.05). In the OMR patients, the antibody response persisted for 2 years, decreased remarkably in the DS patients.

Adult↗

Glycyrrhizin withdrawal followed by human lymphoblastoid interferon in the treatment of chronic hepatitis B.

Seventeen patients with chronic hepatitis B were treated with a 4-week administration of glycyrrhizin followed by a 4-week treatment with human lymphoblastoid interferon, then followed for 6 months after the end of treatment. All were positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B virus-associated DNA polymerase (DNA-p) for at least 6 months before entry. All patients were Japanese and none of them were homosexuals. Eleven patients lost DNA-p activity and 10 of them lost HBeAg. Three of these 10 patients had antibody to HBeAg. In 10 patients who became HBeAg-negative, alanine aminotransferase levels after glycyrrhizin administration were higher and initial DNA-p activities relatively lower than the levels found in seven patients who remained HBeAg-positive. The immunomodulator provided by a short course of glycyrrhizin before administration of human lymphoblastoid interferon may be an effective treatment for patients with chronic hepatitis B.

Adult↗

Decrease of hepatitis A and B virus infections in the population of Okinawa, Japan.

In 1988 1282 serum samples were collected from healthy Japanese persons living on Hateruma Island (574 samples) and Iriomote Island (708 samples) in Okinawa, Japan. Serological markers of hepatitis B virus (HBV) infection [hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc) were investigated and the findings compared with samples taken in 1980 on Hateruma Island and in 1970 and 1980 on Iriomote Island. The samples collected in 1988 on Iriomote Island were also tested for antibody to hepatitis A virus (anti-HAV) and the findings compared with the results of the 1970 and 1980 surveys. The overall prevalence of HBsAg and anti-HBc was 3.7 and 64.8% for Hateruma Island and 3.8 and 44.9% for Iriomote Island. In both areas the overall prevalence of anti-HBc was lower than in 1980, the decrease being significant for the 10-19 year age group on Hateruma Island and the age groups under 39 years on Iriomote Island. The overall prevalence of anti-HAV had fallen to 50.9%. This remarkable decrease had occurred in children and young adults. These data suggest that Virus A (HAV) and HBV infections have dramatically decreased among children in Okinawa within the past 2 decades.

Adolescent↗

Cost effectiveness of intradermal vs. subcutaneous hepatitis B vaccination for the mentally handicapped.

The currently available hepatitis B vaccine is being under utilized for reasons of cost and availability. To address this problem, we performed a recombinant hepatitis B vaccine trial comparing the currently recommended regimen of 10 micrograms subcutaneously (sc) in months 0, 1 and 6 with a more economical regimen of 2 micrograms intradermally (ID) in months 0, 1, 6. This trial assessed the immunogenicity of both regimens in 95 seronegative mentally handicapped patients. Forty four patients (aged 19-55 years, mean age 29.1 years) were vaccinated subcutaneously with recombinant vaccine and 51 (aged 19-52 years, mean age 28.3 years) were given intradermally. We found no significant difference in seroconversion between the subcutaneous group (93.2%) and the intradermal group (96.1%) 12 months after the first vaccination, but the antibody titres were lower in the intradermal group. We feel therefore that the dose should be increased slightly or further injections should be given. As the cost of intradermal vaccination is considerably lower than when using the subcutaneous route, underprivileged patients in institutions could the more readily be immunized against hepatitis B infection.

Adult↗

Quantum chemical study for genotoxic and antitumor activities of hydroxyanthraquinones.

For anthraquinone and its mono- and dihydroxyl derivatives, and for their semiquinone anion radicals, semiempirical MNDO (moderately neglected differential overlap)/H calculations were performed and an attempt was made to correlate the calculated quantum quantities with the genotoxic and the antitumor activities. From these calculations, it was found that the electrophilic frontier electron densities (fE beta) on the beta position in anthraquinones were distinctly correlated with the genotoxic activity. On the other hand, calculations for the semiquinone anion radicals revealed the great stabilizations by the intramolecular hydrogen bond of the carbonyl group with alpha-hydroxyl groups. It has been suggested that this type of stabilization may be associated with the antitumor activity of several hydroxylanthraquinone derivatives.

Anthraquinones↗

Multicenter controlled trial comparing high-frequency jet ventilation and conventional mechanical ventilation in newborn infants with pulmonary interstitial emphysema.

One hundred forty-four newborn infants with pulmonary interstitial emphysema were stratified by weight and severity of illness, and randomly assigned to receive treatment with high-frequency jet ventilation (HFJV) or rapid-rate conventional mechanical ventilation (CV) with short inspiratory time. If criteria for treatment failure were met, crossover to the alternate ventilatory mode was permitted. Overall, 45 (61%) of 74 infants met treatment success criteria with HFJV compared with 26 (37%) of 70 treated with CV (p less than 0.01). Eighty-four percent of patients who crossed over from CV to HFJV initially responded to the new treatment, and 45% ultimately met success criteria on HFJV. In contrast, only 9% of those who crossed over from HFJV to CV responded well to CV (p less than 0.01), and the same 9% ultimately met success criteria (p less than 0.05). Therapy with HFJV resulted in improved ventilation at lower peak and mean airway pressures, as well as more rapid radiographic improvement of pulmonary interstitial emphysema, in comparison with rapid-rate CV. Survival by original assignment was identical. When survival resulting from rescue by the alternate therapy in crossover patients was excluded, the survival rate was 64.9% for HFJV, compared with 47.1% for CV (p less than 0.05). The incidence of chronic lung disease, intraventricular hemorrhage, patent ductus arteriosus, airway obstruction, and new air leak was similar in both groups. We conclude that HFJV, as used in this study, is safe and is more effective than rapid-rate CV in the treatment of newborn infants with pulmonary interstitial emphysema.

Bronchopulmonary Dysplasia↗

Comparative pharmacokinetic properties of murine monoclonal antibody A7 modified with neocarzinostatin, dextran and polyethylene glycol.

The murine monoclonal antibody A7 (Mab A7) was chemically modified with several macromolecules: dextran, polyethylene glycol and the anti-cancer polypeptide neocarzinostatin. The pharmacokinetic properties of the combinations were subsequently examined. Radioimmunoassay revealed that all preparations retained their antigen-binding activities. The Mab A7-neocarzinostatin conjugate was cleared from the blood circulation with a kinetic pattern almost identical to that of the parent Mab A7. Of the three preparations, Mab A7-dextran (A7-Dx) was removed the most rapidly from the circulation. Mab A7-polyethylene glycol (A7-PEG) exhibited the slowest blood clearance curve, with twice the half life of the parent Mab A7 in the circulation. In normal organ distributions, A7-Dx exhibited the highest liver, spleen and kidney uptake, and A7-PEG showed the lowest uptake, when expressed as tissue:blood ratio. Although A7-Dx exhibited lower tumor uptake, there was no significant difference among the three conjugates in tumor-bearing nude mice. A7-PEG seems to be a good candidate for targeted cancer therapy using antibody due to its high blood retention but low normal organ uptake.

Animals↗

Tumor localization and in vivo antitumor activity of the immunoconjugate composed of anti-human colon cancer monoclonal antibody and mitomycin C-dextran conjugate.

The tissue distribution and in vivo antitumor activity of a novel monoclonal antibody-mitomycin C conjugate (A7-MMCD) composed of anti-human MAb A7 and MMC-dextran conjugate were investigated using tumor-bearing mice. A7-MMCD was prepared via an anionic dextran intermediate for the purpose of keeping the non-specific uptake by the reticuloendothelial system to a minimum. 111In-labeled A7-MMCD showed about a 5-times-greater accumulation in SW1116 (targeted tumor) than in S180 (non-targeted tumor) 48 h after injection, and produced a tumor-to-blood ratio which was 3 times higher in SW1116-bearing mice than in S180-bearing mice 96 h after injection. Accumulations in the liver, spleen, and kidney were also observed to some extent. Pharmacokinetic analysis revealed that A7-MMCD had nearly the same properties in the body as MMCDan (MMCD with an anionic charge), i.e., those of a negatively charged macromolecule. Both A7-MMCD and MMCDan had relatively similar tissue uptake rate indices for the liver and spleen. The tumor uptake rate index for SW1116 was about 2.5 times greater than that for S180, and the total amount of 111In-A7-MMCD accumulated in SW1116 was calculated to be approximately 5 times greater than the amount in S180. These results indicated that A7-MMCD could achieve site-specific targeting in the body. Furthermore, in the therapeutic experiment using SW1116 implanted subcutaneously, A7-MMCD suppressed tumor growth significantly, compared to free MMC and MMCDan. These results suggest that in designing an monoclonal antibody-drug conjugate via an intermediary, the physicochemical properties of intermediate macromolecules must also be taken into consideration to obtain a high degree of efficacy in vivo.

Animals↗

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

The new Micro Particle Enzyme Immunoassay technique (MEIA, IMx HBc, Abbott) has been recently introduced for the detection of the antibody to hepatitis B core antigen (anti-HBc). To evaluate the feasibility of using the IMx-HBc, we carried out comparison tests with this method and RIA using various sera. Results obtained were as follows: In the test of 813 sera, 427 (52.3%) were positive by both IMx and RIA, two (0.2%) were positive by RIA only, and the remaining 384 (47.3%) were negative by both methods. A good correlation between IMx and RIA was observed with a coincidence rate of 99.8% and a correlation coefficient of 0.969. Examination of diluted sera using IMx revealed that IMx can be used as efficiently was RIA: high anti-HBc titer was found among HBsAg carriers, but not among non HBsAg carriers. Anti-HBc was assayed within 45 minutes by IMx, and the procedure was simple because of the auto analyser used in this method. These results indicate that the sensitivity of IMx is equivalent to that of RIA, and that it is easier to use than RIA.

Adult↗

[Evaluation of micro particle enzyme immunoassay technique (MEIA)-IMx for the detection of IgM class antibody to hepatitis B core antigen].

The new Micro Particle Enzyme Immunoassay technique (MEIA, IMx HBc-M, Abbott) had been recently introduced for the detection of IgM class antibody to hepatitis B core antigen (IgM anti-HBc). To evaluate the feasibility of using the IMx HBc-M, we carried out comparison tests between this method. RIA and EIA using sera from acute hepatitis B and type B chronic liver disease. Results obtained were as follows: In the test of 98 sera from acute hepatitis B patients, 92 (93.9%) were positive for IgM anti-HBc by IMx HBc-M, 96 (98.0%) by RIA and 82 (83.7%) by EIA. The four sera which were positive by RIA, but not by IMx were ones obtained from 5 to 12 month after onset. In the test of 267 sera from B type chronic liver disease patients, 93 (34.8%) were positive by IMx HBc-M, 109 (40.8%) by RIA and 23 (8.6%) by EIA. There was a difference in the positive rate between IMx HBc-M and RIA among type B chronic liver disease: the positive rate was higher in RIA than in IMx HBc-M among type B active chronic hepatitis, but only a little higher in IMx HBc-M than RIA among hepatocellular carcinoma. IgM anti-HBc titer was significantly higher in acute hepatitis type B than in chronic liver disease, and was so even in the phase of HBsAg negative in acute hepatitis. IgM anti-HBc was assayed within 45 minutes by IMx, and the procedure was simple because of the auto analyser used in this method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[An epidemiologic study of anti-HTLV-I (antibody to human T cell lymphotropic virus type I) by category of disease in the Kushima district of Miyazaki prefecture].

HTLV-I seroprevalence in the southern part of Miyazaki prefecture was reported to be high in many seroepidemiological surveys. In order to determine the distribution of antibody to Human T-cell lymphotropic virus type I (anti-HTLV-I) in the Kushima district of Miyazaki prefecture and evaluate the relation between the HLTV-I carrier and disease, determination of anti-HTLV-I status of patients in a hospital in Kushima City, Miyazaki prefecture was carried out from March to July, 1985. Sera from 542 patients was tested for presence of anti-HTLV-I by particle agglutination (PA) and indirect immunofluorescence (IF). Results obtained area as follows 1) Overall prevalence of anti-HTLV-I was 31.2 per cent (169 of 542 individuals). It increased gradually with age and elevated remarkably in the 60-69 age group, showing the highest rate of 39.6 per cent. 2) Prevalence of anti-HTLV-I was 28.6 per cent (65 of 227) in males and 33.0 per cent (104 of 315) in females. A significant difference by sex was not recognized. 3) No significant difference was found in the geographical distribution of anti-HTLV-I, but prevalence in the Toi area was relatively low. 4) Anti-HTLV-I was prevalent in the patients with tuberculosis (46.2 per cent), most of whom had a history of blood transfusion. In this study, the relation between HTLV-I carriers and diseases was not analysed. 5) Seroprevalence of anti-HTLV-I in the patients who had had blood transfusions was significantly higher than that of those who had not had blood transfusions (p less than 0.01).

Adolescent↗

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

The new Micro Particle Enzyme Immunoassay technique (MEIA, IMx HBsAg, Abbott) has been recently introduced for the detection of the presence of hepatitis B surface antigen (HBsAg). The present trial was carried out to determine the feasibility of using the IMx HBsAg with sera and plasma, and for comparison with RIA (Ausria II, Abbott) and RPHA (Reversecell, Megroken). Results obtained were as follows: In the test of 622 sera from inhabitants in Okinawa, 455 (73.1%) using IMx were positive for HBsAg, 454 (73.0%) with RIA, and 330 (53.0%) with RPHA. Five of the 179 tests using plasma from hemodialysis patients were positive for HBsAg with both IMx and RIA. One of these 5 was negative for HBsAg with RPHA. The difference of HBsAg positive rates between IMx and both RIA and RPHA increased with advancing age. Twenty four individuals were followed up from three to ten years and had had it confirmed that HBsAg had become negative in their sera, HBsAg was still positive from one to four years in both IMx and RIA after HBsAg became negative in RPHA. It was noted that HBsAg was assayed within one hour by IMx, and that the procedure was simple because of the autoanalyser equipped for this method. The results indicate that the sensitivity of IMx might be equal to that of RIA more than that of RPHA, and easier to measure than either of the others.

Adolescent↗