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Biomedical subjects

A Noguchi

Publications and source records attributed to A Noguchi.

At least 55 records · Page 3Linked to original sources

Failure of human immunoresponse to N-glycolylneuraminic acid epitope contained in recombinant human erythropoietin.

Recombinant human erythropoietin (rHUEPO) was produced by Chinese hamster ovary cells and commercially distributed to hospitals by two pharmaceutical companies in Japan ('ESPO' by Kirin Brewery Co. Ltd., and Sankyo Co. Ltd., and 'EPOGIN' by Chugai Pharmaceutical Co. Ltd.) These products contained about 1% N-glycolylneuraminic acid (Neu5Gc) in total sialic acid content. Since humans do not synthesize Neu5Gc, successive injection of Neu5Gc-containing products was feared to lead to allergic-like symptoms. Therefore, serum levels of antibodies of Neu5Gc epitope in 90 patients who received repeated i.v. injections of ESPO or EPOGIN were determined by an enzyme immunoassay using Neu5Gc alpha 2-3Gal beta 1-4Glc-Cer, GM3(Neu5Gc), as an antigen and compared with those in 100 healthy persons. Either no or low antibody levels were detected in both groups with no significant difference. In 40 patients who received s.c. injections of ESPO or EPOGIN, serum HD antibody levels were determined before and after weekly therapeutic injections carried out for one to several months, but no significant elevations were detected in all patients. The above results indicated that therapeutic administration of rHuEPO to patients to patients with chronic renal failure is safe from allergic-like side effects associated with the production of Neu5Gc-specific antibodies, and it was concluded that Neu5Gc epitope of rHuEPO is minimally antigenic in humans.

Adolescent↗

Sexual transmission of human T-lymphotropic virus type I among female prostitutes and among patients with sexually transmitted diseases in Fukuoka, Kyushu, Japan.

The authors investigated the prevalence of antibody to human T-lymphotropic virus type I (anti-HTLV-I) in 409 female prostitutes, 446 patients with an episode of sexually transmitted diseases, and 17,345 control blood donors. All subjects were Japanese and all studies were done in Fukuoka, Kyushu, Japan, in 1989. The prevalence of anti-HTLV-I was significantly higher in the prostitutes (5.1%, p < 0.001), in the male patients (2.8%, p < 0.05), and in the female patients (5.7%, p < 0.05) than in the controls (males 1.4%, females 2.2%). Prevalence of anti-HTLV-I in the prostitutes increased with the number of years spent in prostitution, but the increase was not statistically significant. Among the subjects with sexually transmitted diseases, female prostitutes with syphilis, male patients with non-gonococcal urethritis, female patients with syphilis, and female patients with gonorrhea had a significantly higher prevalence of anti-HTLV-I than did the controls. A longitudinal study was done on the 168 prostitutes. Two (1.3%) of the 158 initially seronegative subjects seroconverted over the period of 2 years. These data suggest that the risk of male-to-female transmission of HTLV-I through sexual contact is high among high risk groups in Japan, and they support the possibility of female-to-male transmission of HTLV-I.

Adolescent↗

Evidence for a free N-acetylneuraminic acid-hydroxylating enzyme in pig mandibular gland soluble fraction.

The activity of a free N-acetylneuraminic acid (Neu5Ac)-hydroxylating enzyme which converted Neu5Ac into N-glycolyl-neuraminic acid (Neu5Gc) was demonstrated in the soluble fraction of pig mandibular gland. The hydroxylation was possible only with NADPH as the electron donor. The apparent Km was 4.5 mM Neu5Ac. At 0.5 mM monovalent cations had no effect on the hydroxylation of Neu5Ac whereas bivalent cations gave varied inhibition capacities ranging from 14 to 75%. EDTA gave a time-dependent enhancement of activity. It was concluded that the enzyme does not require an exogenously added inorganic cofactor. Results from salt fractionation of the soluble fraction and the use of inhibitors such as mercurials suggested that the hydroxylation of Neu5Ac to Neu5Gc may involve other, as yet unknown, component(s) and the possibility of electrons donated by NADPH being transferred to activated molecular oxygen (second substrate). We propose to name this enzyme N-acetyl-neuraminic acid hydroxylase.

Animals↗

Immunogenicity of N-glycolylneuraminic acid-containing carbohydrate chains of recombinant human erythropoietin expressed in Chinese hamster ovary cells.

Recombinant human erythropoietin (EPO) produced by Chinese hamster ovary cells and distributed by two different pharmaceutical companies were confirmed to contain about 1% N-glycolylneuraminic acid (Neu5Gc) in total sialic acid content. Since chickens, like humans, do not synthesize Neu5Gc, they were used to determine the immunogenicity of Neu5Gc epitope in EPO. Chickens immunized with EPO did not produce significant titer of antibody that was specific to GM3(Neu5Gc) as compared to antibody titers produced in chickens immunized with fetuin containing 7% Neu5Gc or GM3(Neu5Gc) containing 100% Neu5Gc. Results obtained by an ELISA inhibition test showed that EPO, compared to GM3(Neu5Gc), reacted almost one thousand times less strongly with a human Hanganutziu-Deicher (HD) antibody. This study implies that an increase of Neu5Gc content in a molecule enhances its HD antigenicity. The response to Neu5Gc in patients receiving therapeutic injections of EPO is currently under investigation.

Animals↗

Human T-lymphotropic virus type-I, and hepatitis A, B and C viruses in Nepal: a serological survey.

In 1987, 676 blood samples were collected from inhabitants of the Bhadrakali and Kotyang villages in Nepal. The samples were tested for the prevalence of antibody to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), second-generation antibody to hepatitis C virus (anti-HCV) and antibody to human T-lymphotropic virus type-I (anti-HTLV-I). Anti-HAV was present in 99.3% of the people surveyed. The prevalence of anti-HAV reached 100% in the < 25 age group and was as high or only slightly lower in all other age groups. The prevalence of HBsAg was 0.3% and of anti-HBc 7.7%. Anti-HCV was found in 0.1% of the residents. No significant difference by gender or village was noted in the prevalence of anti-HAV, HBsAg, anti-HBc, or anti-HCV. No anti-HTLV-I-positive persons were identified. These data suggest that the prevalence of hepatitis B and C virus infections in Nepal is low in contrast to hepatitis A virus infection, and that human T-lymphotropic type-I infection may be absent in this population.

Adolescent↗

[Changes of liver function measured by 99mTc-GSA scintigraphy after hepatectomy].

In 14 patients with hepatic tumors, liver volume and liver function indices were studied by 99mTc-GSA liver scintigraphy before and after hepatectomy. The liver volume measured by 99mTc-GSA SPECT was significantly decreased after surgery in all 14 patients (p < 0.001). Postsurgically, 7 patients showed an increase of greater than 10% in the LU15 value, while 3 showed a decrease of 10% in the LU15 value, while 3 showed a decrease of 10%. Two patients showed a decrease of greater than 10% in the HH15 value after surgery. The changes in LU15 after surgery were inversely correlated with those in HH15. The present findings clarified that in several cases of surgically treated hepatic tumors, 99mTc-GSA indices of liver function generally thought to indicate the size of the functioning liver cell mass were distinctly improved after surgery in comparison with those before surgery, despite the postoperative decrease in the liver volume. Furthermore, the results of a 99mTc-GSA SPECT study separately measuring the volume of the unilateral hepatic lobe and its radioactivity uptake, indicated that regeneration of the functioning liver cells often occurred in the entire liver. 99mTc-GSA scintigraphy appears to be a valuable method for evaluating changes in both the liver volume and the liver function indices after hepatectomy.

Aged↗

Identification of a specific receptor for interstitial collagenase on osteoblastic cells.

We have previously shown that the rat osteoblastic cell line UMR 106-01 responds to parathyroid hormone treatment by secreting interstitial collagenase. Secreted collagenase reaches a maximal concentration 12-24 h after parathyroid hormone stimulation, but then declines to undetectable levels by 96 h. Neither spontaneous nor cell-mediated extracellular degradation could account for this disappearance, since the enzyme maintained stability in both fresh and conditioned media. Instead, a cell-mediated binding mechanism was suggested by the rapid and saturable removal of exogenous purified rat collagenase at 37 degrees C. Binding studies using 125I-collagenase at 4 degrees C indicated a saturable receptor of a single class and 12,000 receptors per cell (Kd = 5 x 10(-9) M). A time course revealed specific receptor-mediated binding within 10 min and equilibrium by 60 min, while dissociation experiments further demonstrated reversibility. The kinetics of 125I-collagenase binding are characterized by the association (k1 = 4 x 10(6) M-1 min-1) and dissociation (k-1 = 2 x 10(-3) min-1) rate constants. The receptor was shown to be specific for rat collagenase since a host of related and unrelated proteins failed to compete for binding. Internalization studies revealed maximal intracellular accumulation at 30 min and complete degradation by 90 min, suggesting this receptor functions in these osteoblastic cells to eliminate extracellular collagenase.

Animals↗

Predictive capabilities of preoperative and postoperative pulmonary function tests in delayed repair of congenital diaphragmatic hernia.

To improve the survival of newborns with congenital diaphragmatic hernia (CHD), preoperative stabilization with conventional ventilatory therapy and extracorporeal membrane oxygenation (ECMO) have been used. Measurements that quantify pulmonary function may allow an accurate assessment of lethal pulmonary hypoplasia and predict outcome. Pulmonary function tests (PFTs) were obtained in 20 infants preoperatively and postoperatively; these included measurements of compliance, dynamic compliance, and tidal volume. Overall survival was 75%. Six surviving infants were initially managed with ventilator therapy alone, followed by repair (group 1). The remaining 14 patients, who were moribund at presentation or whose initial ventilator therapy failed, were placed on ECMO and received repair during bypass; nine survived (group 2), and five died (group 3). Compliance, dynamic compliance, and tidal volume obtained at initial presentation and immediately preoperatively were significantly higher for group 1 as compared with groups 2 and 3. Infants whose initial compliance was greater than 0.25 mL/cm H2O/kg and initial tidal volume was greater than 3.5 mL/kg did not require ECMO. Ultimate improvement in compliance was noted in 5 of 6 patients in group 1, 8 of 8 patients in group 2, and 5 of 5 in group 3. This improvement followed an initial decline in compliance in 9 of 14 survivors, from 15% to 76%. All six patients in group 1 had tidal volumes of more than 4 mL/kg, as did 7 of 9 patients in group 2. Only one patient among the ECMO nonsurvivors (group 3) had a postoperative tidal volume of this magnitude. These data suggest that initial PFTs may predict which infants will require ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal Membrane Oxygenation↗

HBsAg subtypes among HBsAg carriers in Okinawa, Japan. Evidence of an important relationship in seroconversion from HBeAg to anti-HBe.

In Okinawa, Japan 1261 hepatitis B surface antigen (HBsAg) carriers were investigated for clinical differences among HBsAg subtypes. Among the 854 for whom they could be determined, subtype adw was found in 604 (70.7%), adr in 232 (27.2%) and others in 18 (2.1%). The overall prevalence of hepatitis B e antigen (HBeAg) was significantly lower in subtype adw (11.9%) than in adr (17.7%) (P < 0.01). The mean age of HBeAg-positive carriers was significantly lower in adw (20.4 years) than in adr (26.9 years) (P < 0.05). Seroconversion from HBeAg to antibody to HBeAg (anti-HBe) occurred in 43 carriers. The seroconversion rate was higher in adw (43.1%) than in adr (29.3%) and the seroconversion age was younger in adw (22.7 years) than in adr (27.9 years). These results suggest that carriers with subtype adw tend to seroconvert from HBeAg to anti-HBe at a higher rate and a younger age than do those with adr. HBsAg subtypes may be closely associated with the HBeAg/anti-HBe status.

Adolescent↗

Purification and characterization of a novel acrosin-like enzyme from boar cauda epididymal sperm.

A trypsin-like protease was extracted with 1% cetyltrimethylammonium bromide (CTAB) at pH 7.0 from boar cauda epididymal sperm nuclei whose acrosin had previously been removed by acid extraction. The CTAB-extracted sperm protease (CSP) was purified by ion-exchange chromatography on CM-23, gel filtration on Sephadex G-100, affinity chromatography on benzamidine-CH-Sepharose 4B, and HPLC on CM-5PW. CSP is a two chain protein composed of M(r) 2.6K and M(r) 37K chains, which are covalently cross-linked by disulfide bonds. CSP exhibited a pH optimum between pH 8.0 and 9.0, and was inhibited by diisopropyl phosphorofluoridate, antipain, leupeptin, and 1-chloro-3-tosylamide-7-amino-L-2-heptanone. The activity of CSP was enhanced about 1.2-fold with 50 mM CaCl2, with which acrosin is enhanced 2.0-fold. The catalytic efficiency (kcat/Km) of CSP toward Bz-L-Arg-OEt, Tos-L-Arg-OMe, and Tos-L-Lys-OMe in the presence of 50 mM CaCl2 differed from that of acrosin by factors of 0.53, 1.2, and 0.80, respectively. Amino acid sequencing of V8-digested peptides of CSP, and its L- and H-chains showed that the amino acid sequence of CSP was closely related to, but different from, that of acrosin. These results suggest that CSP is a novel acrosin-like enzyme that differs from acrosin in its location in the sperm head, the effect of calcium ions on its activity, and its substrate specificity.

Acrosin↗

[A four year follow-up study of recombinant HB vaccine--comparisons between three doses of subcutaneous injections and additional low dose intradermal injection].

To determine the efficacy of an additional low dose of intradermal injection of recombinant HB vaccine administered to nonresponders in addition to the standard three injections, we investigated the anti-HBs positive rate and titer of anti-HBs after four years among 58 subjects who did not develop antibodies after three doses of subcutaneous injections and who did develop the antibody after an additional low dose intradermal injection (Nonresponders), and compared them with 150 subjects who developed anti-HBs after three doses of subcutaneous injections (Responders). Fifty four subjects who were negative after four years were revaccinated with one or three doses of the subcutaneous injection. Anti-HBs positive rates after four years were 56.0 percent in Responders and 56.9 percent in Nonresponders, showing no differences. Eighty eight percent of 54 subjects who were given one or three doses of the vaccine developed anti-HBs. There were no differences in the antibody rates or titer of the antibody between the one and three doses groups. The decrease in titer of antibody was related to the levels initially having the most marked decrease in the level four years later. From these findings, we concluded that there were no differences of anti-HBs positive rates or antibody titer after four years in Responders and Nonresponders, and that one additional dose of the vaccine may be effective four years after initial administration among both groups.

Adult↗

[Evaluation of immunochromatography assay technique for detection of hepatitis B surface antigen].

A new immunochromatography assay technique (DAINASCREEN HBsAg, Dainabot) has been recently introduced for the detection of the presence of hepatitis B surface antigen (HBsAg). To evaluate the feasibility of using the DAINASCREEN HBsAg, we carried out comparison tests with this method and RPHA. Results obtained were as follows: In a test of 692 sera from inhabitants in Iki island, Nagasaki Prefecture, 24 (3.5%) were positive for HBsAg by both DAINA and RPHA. Twenty-four patients with hepatitis B were all positive in both methods. Thirty patients with autoimmune diseases and eight who had accidental needle exposure to the blood of patients with HBV infection were negative by both methods. Six individuals were followed over a period of 10 years and all eventually eliminated HBsAg from their sera. In four patients, HBsAg remained positive by DAINA at one yearly check after it had become negative by RPHA. In five patients, HBsAg remained positive by RIA and IMs after DAINA and RPHA had become negative. A good correlation was observed between DAINA and RPHA with a concordance rate of 99.5%. A good correlation of HBsAg titer between the two methods was observed and found to be significant (r = 0.87, p < 0.001). HBsAg assay was able to be completed within 15 minutes by DAINA and the procedure was simple. These results indicate that the sensitivity of DAINA is superior to RPHA and it is easy to use.

Adolescent↗

Increased lactic dehydrogenase (LDH)-linked immunoglobulin associated with interferon-alpha therapy in a case of chronic hepatitis C.

A 47-year-old man diagnosed as having chronic hepatitis C was admitted to our hospital where he was treated with interferon (IFN)-alpha. After initiation of this treatment, his serum LDH became elevated, and when the drug was stopped, it decreased gradually to within the normal range. The histopathological findings and the liver function were not aggravated. The administration of IFN-alpha showed a correlation to LDH-linked immunoglobulin, a complex of LDH and immunoglobulin, often causing high levels of LDH. In patients on IFN therapy with elevated LDH, LDH-linked immunoglobulin should be tested.

Antigen-Antibody Complex↗

Prevalence of antibody to human T-cell lymphotropic virus type I in Okinawa, Japan, after an interval of 9 years.

To clarify events related to age dependence of human T-cell lymphotropic virus type I (HTLV-I) seroprevalence, the authors carried out two seroepidemiologic studies at a 9-year interval on residents of Yonaguni Island, Okinawa, Japan. The overall prevalence was 17.8% (345/1,943) in 1980 and 17.1% (264/1,543) in 1989-1990. The authors studied the relation of the HTLV-I infection rate to the birth year of 967 individuals tested in both years. Of the 967 individuals, 209 were positive for anti-HTLV-I in the 1980 survey. By the 1989-1990 survey, only 7 of the 758 anti-HTLV-I negative cases (0.9%) had become positive for anti-HTLV-I, and all 7 were over 40 years of age. For persons born in the same period, there was almost no difference between the prevalence of HTLV-I found in the 1980 survey and that found in the 1989-1990 survey. These data show that there were few new cases of HTLV-I infection and none in the lower age groups over the 9 years, which suggests that higher rates of HTLV-I infection in adults reflect past higher rates of infection as infants.

Adolescent↗

The role of monoclonal antibody A7 as a drug modifier in cancer therapy.

An anticancer antibiotic, neocarzinostatin (NCS), was covalently conjugated to the murine monoclonal antibody A7 (mAb A7), which recognizes the glycoprotein on the cell surface of human colon cancer. The biological and pharmacological properties of the conjugate (A7-NCS) were examined and compared with those of unconjugated NCS. A7-NCS exhibited a strong binding and cytotoxicity to the cell and an antigen-specific tumor accumulation. Significant tumoricidal effects in vivo were observed in the antigen-positive tumor-bearing mice treated with A7-NCS, whereas NCS mixed with mAb A7 and NCS alone were relatively ineffective. In the antigen-negative tumor, the tumoricidal effect of A7-NCS was lower than in the antigen-positive tumor. The NCS concentration in blood and tumor were significantly elevated by conjugation to mAb A7. The NCS localization in tumor was higher in the antigen-positive tumor than in the antigen-negative tumor. Death due to acute toxicity was observed at a dose of 20 units (U) NCS in mice treated with unconjugated NCS, whereas toxicity was seen with a much higher dose of NCS (100 U) if the drug was conjugated to the mAb. These findings show that mAb A7 confers more favorable pharmacological properties on an anticancer drug, making it potentially more useful for cancer chemotherapy.

Animals↗

Low prevalence of hepatitis C virus infection among hospital staff and acupuncturists in Kyushu, Japan.

During 1987 and 1988, samples of serum were collected from 1097 members of the staff of four prefectural hospitals in Miyazaki prefecture and from 183 acupuncturists in Fukuoka City, Japan. The staff included both surgical and non-surgical doctors, radiographers, physiotherapists, nurses, laboratory technicians and others. The samples were tested for the following hepatitis C virus (HCV) markers; antibodies to c100 (anti-c100) by means of enzyme-linked immunosorbent assay (ELISA) with supplementary recombinant immunoblot assay as well as antibodies to the GOR epitope (anti-GOR), also by means of ELISA. Anti-c100 was present in 1.7% of the doctors, radiographers and physiotherapists, in 1.3% of the nurses and in 2.2% of the acupuncturists. These prevalences were slightly higher than those in the controls but the differences were not statistically significant. Anti-c100 was not detected in any laboratory technician or other member of the hospital staff. For an accurate determination of the prevalence of HCV infection, the combined rate of anti-c100 and/or anti-GOR was also calculated. The combined prevalence of HCV infection was 4.3% in medical staff, 2.2% in nurses and 5.5% in acupuncturists. The prevalence of HCV infection among those with direct contact with patients was higher than that of the controls but without statistical significance. In the cohort we examined, the occupational risk of HCV infection was low.

Acupuncture Therapy↗