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Biomedical subjects

Y Kusumoto

Publications and source records attributed to Y Kusumoto.

At least 19 recordsLinked to original sources

Accelerated declining tendency of human T-cell leukemia virus type I carrier rates among younger blood donors in Kumamoto, Japan.

The annual age- and sex-specific human T-cell leukemia virus type I carrier rate of blood donors in Kumamoto, Kyushu, Japan from 1986 to 1990 revealed that the carrier rates of all the age groups below 50 years declined linearly in both sexes (P less than 0.005). Furthermore, the annual declining rates relative to the carrier rates of 16-19-year-old and 20-29-year-old males were higher than those of all of the older males (P less than 0.02), and all female age groups below 50 years had higher relative declining rates than 50-64-year-old females (P less than 0.05). Although several factors, such as a notification program at obstetric clinics, methodological and technical improvement of the assays, wider knowledge of human T-cell leukemia virus type I infection in the latter years, and immigration of individuals from a nonendemic area, might cause an absolute decline of the carrier rate of the blood donors, these factors could not explain the acceleration of the relative declining rate among younger donors. Therefore, this acceleration represents the tendency of the general population.

Adolescent

Induction of mucosal and serum immune responses to a specific antigen of periodontal bacteria.

The dynamics of the host immune response to periodontal bacteria not only may be informative from the standpoint of specific mucosal protection to these pathogens, but also may reveal the capacity of the mucosal immune response to provide protection of the host. To this end, we have examined the immune response to chromatographically purified fimbriae of P. gingivalis administered orally or systemically with liposomes and adjuvant in BALB/c mice, high responders to this antigen. Oral administration of P. gingivalis fimbriae clearly enhanced the fimbriae-specific salivary IgA response. ELISPOT analysis revealed that significant numbers of fimbriae-specific IgA SFC were seen in lamina propria and mesenteric lymph nodes but not in Peyer's patches of mice immunized orally. In contrast, antigen-specific IgM and IgG SFC were seen mainly in the circulating blood mononuclear cells. On the other hand, subcutaneous injection of fimbriae with GM-53 also raised the fimbriae-specific IgG followed by IgM and IgA responses in serum, and both IgA and IgG responses in saliva. Oral immunization was less effective than subcutaneous injection in terms of the serum antibody response. However, the salivary antibody level of mice injected subcutaneously was similar to that of mice immunized orally. In the subcutaneously immunized mice, fimbriae-specific SFC were detected in the spleen, blood, and brachial lymph nodes by ELISPOT assay. Fimbriae-specific IgM SFC appeared earlier and antigen-specific IgG SFC were seen later. These results show that the combined use of fimbriae together with the adjuvant results in sharply increased IgA responses in saliva and IgG responses in serum. In summary, it is clear that the nature of the host's antibody response in serum and mucosal secretions is distinct, and depends on the route of antigen administration, the use of adjuvant and/or liposomes, and the temporal phase of the humoral immune response following various immunization regimes.

Animals

Evaluation of three hepatitis C virus-related antibodies C100, KCL-163, JCC. Tests for screening blood donors.

To evaluate the most effective method for detecting hepatitis C virus (HCV) carriers in a large population of blood donors, HCV-related antibodies were measured in 919 donor serum samples using three different enzyme-linked immunosorbent assays. The antibodies were C100 and KCL-163, nonstructural proteins of HCV, as well as JCC, a translation product of the presumptive HCV core gene. Fourteen (1.5%), 12 (1.3%), and 13 (1.4%) specimens were positive for anti-C100, anti-KCL-163, and anti-JCC, respectively. HCV RNA was detected by the polymerase chain reaction in seven (25.0%) of the 28 specimens that were anti-HCV-positive by at least one of the three assays. Four of the seven specimens were detected by anti-C100 screening, while the remaining three were not. All seven specimens were positive for KCL-163 and/or JCC antibodies. These findings suggest that screening for both KCL-163 and JCC antibodies may be of particular use in accurately identifying HCV-positive blood.

Adult

Occurrence of antigen-specific B cells following oral or parenteral immunization with Porphyromonas gingivalis fimbriae.

The induction and distribution of antigen-specific antibody-secreting cells in various tissues were assessed in BALB/c mice immunized with the purified fimbrial protein of the Porphyromonas gingivalis strain 381. Groups of mice were immunized by gastric intubation of liposomes containing fimbriae and GM-53 on days 0, 1, 27, and 28. Additional groups of mice were immunized with P. gingivalis fimbriae and adjuvant GM-53 in Freund's incomplete adjuvant by subcutaneous injection on days 0 and 28. In the latter group of mice, levels of serum IgM anti-fimbria antibodies were first detected on day 7, while high levels of serum IgG anti-fimbria antibodies were seen after secondary immunization. Fimbria-specific spot-forming cells (SFC) were detected in the spleen, circulating blood mononuclear cells (CBMC), and brachial lymph nodes of immunized mice by ELISPOT. Fimbria-specific IgM SFC appeared by day 5 and antigen-specific IgG SFC were seen later in subcutaneously immunized mice. Mice immunized orally exhibited serum anti-fimbria IgG and IgA antibodies after boosting. Although numerical analysis revealed that the numbers of fimbria-specific SFC were generally lower than in subcutaneously immunized mice, significant numbers of antigen-specific IgA SFC were seen in lamina propria and mesenteric lymph nodes of orally immunized mice. In contrast, antigen-specific IgM and IgG SFC were observed mainly in CBMC. The route of immunization with fimbriae and GM-53 also influenced the total numbers of immunoglobulin-secreting cells. Thus, subcutaneous immunization enhanced the total number of IgM and IgG SFC, including fimbria-specific antibody-secreting cells in CBMC and the spleen. (ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

[Effect of meropenem on fecal flora in children].

Meropenem (MEPM, SM-7338), a novel parenteral carbapenem antibiotic, was examined for its effect on intestinal flora in children. Seven children with infectious diseases (3 male and 4 female children of age's ranging from 4 months to 8 years and 9 months weighing from 7.3 to 23.0 kg) were treated with MEPM at doses ranging 10.3 to 40.5 mg/kg 3 or 4 times a day for 6 to 12 days. Before, during and after the treatment, identities and numbers of various bacteria contained in 1 g of feces were determined and fecal beta-lactamase activity and Clostridium difficile D-1 antigen were also assayed. Changes in fecal flora during MEPM treatment was somewhat different depending on cases. Regarding Enterobacteriaceae among aerobes, all of 7 cases exhibited moderate or pronounced reductions in Escherichia coli. Some of the cases exhibited the tendency to increase in Klebsiella oxytoca. Enterobacter cloacae and Citrobacter freundii. E. coli which was reduced during the treatment increased rapidly after the treatment in 5 out of 7 cases, and the initial bacterial counts were restored. Diverse strains were observed within the genus Enterococcus, while the overall bacterial counts of this genus exhibited the tendency to increase during the treatment. As a result, no significant change in total aerobe count was observed in any case except 1 case where Enterococcus count was somewhat reduced. Among anaerobes, major bacteria such as Bacteroides, Bifidobacterium, Eubacterium and Peptococcaceae exhibited tendencies to decrease in some cases during the antibiotic treatment. Two infants and 1 child exhibited significant decreases in total anaerobe counts. In most of the cases, such changes in major anaerobes were transient and bacterial counts recovered to their initial values rapidly after completion of the treatment. In no cases, glucose non-fermentative Gram-negative bacilli or fungus became predominant. Although C. difficile D-1 antigen was observed in 4 cases, its changes had no relationship with characteristics of feces. C. difficile was not detected in any of the cases. MEPM was detected in feces in 4 cases being treatment, in concentrations ranging from 0.35 to 66.0 micrograms/g. Fecal MEPM levels were very low except in 1 case in which beta-lactamase was negative. From these results, effects of MEPM on intestinal flora in children were relatively minor compared to other new beta-lactam drugs. However, a care should be taken to minimize diarrhea and bacterial turnover when a prolonged use of the antibiotic, was practiced because of potential significant effects on intestinal flora.

Age Factors

[The influence of cefprozil on intestinal bacterial flora].

Cefprozil (CFPZ, BMY-28100), a new oral cephalosporin antibiotic, was studied for its effect on the intestinal bacterial flora in pediatric patients. The subjects were children admitted for infections (2 males and 2 females, 9 months to 6 years 3 months old, weighed 4.3 to 19.0 kg). CFPZ granule was orally administered at a dose between 10.0 to 11.6 mg/kg, 3 doses daily, over 4 to 14 days. The feces from these children were collected before, during and after administration, and bacteria were identified and counted. CFPZ concentration, beta-lactamase activity were also assayed. Bacterial flora in feces during CFPZ administration showed some variance, but no significant change was observed in main aerobes and anaerobes. And in no case, glucose nonfermentative Gram-negative bacilli or fungi were found dominant. beta-Lactamase activity was positive in the feces in all cases. CFPZ concentrations were not detectable in feces before, during and after administration. The above results suggest that CFPZ is a drug with little influence on the intestinal bacterial flora in children.

Administration, Oral

[The influence of cefdinir on the intestinal bacterial flora].

The influence of cefdinir (CFDN), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CFDN in fine granules was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organism: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No remarkable changes were observed in the fecal viable cell counts except that decreases in E. coli counts were observed on the day 3 to 5 after starting administration. The subjects in pediatric study were 7 children with infections, 3 boys and 4 girls, with their ages from 6 months to 12 years 7 months. Their body weights ranged from 5.5 to 29.2 kg. CFDN fine granules was administered at each dose of 3.0 mg/kg to 3.7 mg/kg, 3 times a day for 4 to 14 days. During the administration of CFDN, some variations were observed in the pattern of changes in the fecal bacterial flora between subjects. Although Enterobacteriaceae and total counts of anaerobes were markedly decreased in 2 cases, total counts of aerobes were unchanged in the 2 cases, whereas main aerobes and anaerobes except enterococci hardly varied in the other cases. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant species continually. Although Clostridium difficile and C. difficile D-1 antigens were detected in 1 and 4 cases, respectively, no relationship was found between the number of C. difficile and the characteristics of the feces. With regard to the drug sensitivities of bacteria isolated from feces before and after administration of CFDN, higher levels of resistance were found in some bacteria such as Enterococcus and Bacteroides during or after administration than before administration. CFDN was detected in fecal samples from 2 cases during administration with concentrations ranging between 0.99-254 micrograms/g. High value of CFDN was found in a case with low beta-lactamase activity in feces, in which marked decrease of Enterobacteriaceae and total counts of anaerobes was observed. The above results suggest that CFDN is considered to be a drug with relatively small influence on the intestinal bacterial flora. But as high concentrations of drugs were detected in feces under some circumstances, our attention will be required. Particular care is also required for the occurrence of diarrhea and microbial replacement during continuous, long-term administration of the drug.

Animals

Immunobiological activities of synthetic peptide segments of fimbrial protein from Porphyromonas gingivalis.

Several oligopeptide segments of fimbrial subunit protein (fimbrilin) of Porphyromonas gingivalis strain 381 were synthesized and tested for immunobiological activities. Peptides F3(31-50; amino acid residue numbers 31 to 50, based on the amino acid sequence of the fimbrilin proposed by Dickinson et al., Infect. Immun., 170, 1658, 1988), F12(212-231) and F17(312-331) were found to be immunodominant epitopes of this fimbrial protein as revealed by ELISA. Furthermore, peptides F5(71-90) and F17(312-331) were demonstrated to agglutinate rabbit erythrocytes, and were mitogenic for BALB/c spleen cells but not thymocytes. These peptides enhanced the number of fimbria-specific antibody-secreting cells in BALB/c spleen cell cultures, and induced cytokines such as tumor necrosis factor-alpha and interleukin-6 production in human monocyte/macrophage cultures. The data demonstrate that these defined peptide segments are responsible for the immunostimulating portions within the fimbrial protein molecule.

Amino Acid Sequence

Evaluation of nontumorous tissue damage by transcatheter arterial embolization for hepatocellular carcinoma.

The serial changes in serum hepatic enzyme activities by transcatheter arterial embolization (TAE) were analyzed in 17 patients with hepatocellular carcinoma to estimate the contribution to the value by the damage of tumor or nontumorous hepatic cells. The serum levels of relatively tumor-specific fructose 1,6-diphosphate (FDP) aldolase were elevated after TAE in the cases of both superselective and nonsuperselective TAE that were performed from the segmental and the nonsegmental hepatic artery, respectively, but we found the marked elevation of FDP aldolase in the cases of the superselective TAE. In contrast, the non-tumor-specific fructose 1-phosphate (F1P) aldolase was markedly elevated only in the cases of nonsuperselective TAE. The total amount of FDP aldolase released by TAE correlated significantly with the integrated tumor tissue volume (P less than 0.005), whereas the total amount of F1P aldolase output correlated significantly with the integrated nontumorous tissue volume (P less than 0.005) as defined by lipiodol accumulation on computerized tomography scan. The consequent changes in the total nontumorous liver volumes after TAE were also analyzed by the follow-up computerized tomography scan. The nonsuperselective TAE caused the significant total nontumorous liver atrophy when compared with the superselective TAE. The progression of the total nontumorous liver atrophy correlated significantly with F1P aldolase output by TAE (P less than 0.001) but not with FDP aldolase output. These results suggest that the outputs of FDP and F1P aldolase are useful to estimate the degree of the tumorous and nontumorous tissue damage by TAE, respectively, and F1P aldolase output can be used to predict the progression of liver atrophy caused by TAE.

Adult

Transforming growth factor beta 1 differentially regulates alpha-fetoprotein and albumin in HuH-7 human hepatoma cells.

Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit hepatocyte growth in vitro and in vivo. In this study, we analyzed the effect of TGF-beta 1 on alpha-fetoprotein (AFP) and albumin gene expression in HuH-7 human hepatoma cells. TGF-beta 1 inhibited cell growth in a dose dependent manner. The cellular secretion rate of AFP but not albumin was suppressed significantly by TGF-beta 1. TGF-beta 1 caused a significant reduction in the level of AFP mRNA. In contrast, the levels of albumin mRNA or beta-actin mRNA were not changed by TGF-beta 1. In transient transfection experiments, TGF-beta 1 resulted in selective repression of AFP promoter activity. These results suggest that TGF-beta 1 is one of the key factors involved in the differential regulation of the AFP gene and the albumin gene.

Carcinoma, Hepatocellular

Follow-up of asymptomatic HTLV-I carriers among blood donors in Kyushu, Japan.

We examined mortality from adult T-cell leukemia/lymphoma (ATL/ATLL) and other diseases alleged to be associated with human T-lymphotropic virus type I (HTLV-I) among anti-HTLV-I antibody-positive blood donors in Kyushu, Japan. During 1984-87, a total of 3,991 blood donors aged 40 years or over were followed from the date of donation to the date of death or the end of the study. Crude mortality rates from ATL (with 95 percent confidence intervals) were 68 per 100,000 (13-202) for males and 36 per 100,000 (3-132) for females. The rates were underestimated by approximately 50 percent because of self-selection and short observation periods. Neither death rates from other cancers nor death rates from all cancers were elevated.

Adult

Different B-cell responses to human T-cell lymphotropic virus type I (HTLV-I) envelope synthetic peptides in HTLV-I-infected individuals.

HTLV-I (human T-cell lymphotropic virus type I) is the retrovirus related to two distinct diseases, adult T-cell leukemia/lymphoma (ATLL) and HTLV-I-associated myelopathy (HAM). We analyzed the difference in antibody activities against the viral protein and the difference in specificities of anti-HTLV-I envelope antibodies among HTLV-I-infected individuals from the same HTLV-I-endemic area using a HTLV-I-gag-env hybrid protein and HTLV-I-env-encoded synthetic peptides as antigens, respectively. The difference in the responses of IgG anti-HTLV-I envelope antibody production among HTLV-I-infected individuals was qualitative as well as quantitative. Sera from patients with HAM showed significantly higher activities of antibodies against HTLV-I-gag-env hybrid protein than sera from other HTLV-I-infected individuals including ATLL patients. The specificities of IgG anti-HTLV-I-envelope antibodies, tested on seven synthetic envelope peptides, were directed mainly against four sites, V1E7 (residues 97-111), V1E8 (191-209), and V1E9 (268-286) on gp46 and V1E1 (342-363) on gp21. Three of these sites were shown to be immunodominant T-cell sites in mice in our previous study. Whereas patients in all categories made antibodies specific for V1E1 and V1E8, only HAM patients made antibodies to the V1E7 and V1E9 epitopes, suggesting a qualitative difference in response. Whether this difference is of pathogenetic significance is not clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Variations in radioimmunoscintigraphic detection of tumor showed by five monoclonal antibodies to carcinoembryonic antigen.

Radioimmunoscintigraphy using mouse monoclonal antibodies to various parts of a carcinoembryonic antigen (CEA) molecule was performed. Four radiolabeled antibodies (F4-82, 28A, F3-30, F33-104) were injected into tumor transplanted nude mice to compare the accumulation of these antibodies in tumors. The four antibodies were accumulated selectively in CEA- producing tumors. The tumor visualization correlated with the tumor/blood radioactivity ratio, whereas the tumor/blood radioactivity ratio did not correlate with the in vitro percent binding to tumor cells or the in vivo percent injected dose in CEA-producing tumors. Among the four antibodies, F33-104 showed the highest tumor/blood radioactivity ratio and the best image quality in any CEA-producing tumor. These results suggest that the antibody which has a high tumor/blood ratio rather than high total tumor uptake may be useful for radioimmunoscintigraphy.

Animals

Increase in tumor necrosis factor alpha- and interleukin-6-secreting cells in peripheral blood mononuclear cells from subjects infected with Mycobacterium tuberculosis.

We detected and quantified tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) from monocytes/macrophages (M phi) in the peripheral blood of subjects from three different population groups, i.e., tuberculin-negative healthy subjects, tuberculin-positive healthy subjects, and patients with active pulmonary tuberculosis. TNF-alpha or IL-6 activity in the culture supernatant of these cells was determined by the cytotoxicity of murine L-929 cells or by enzyme-linked immunosorbent assay, respectively. Detection and enumeration of cells secreting either TNF-alpha or IL-6 were performed by an adaptation of the enzyme-linked immunospot assay. Monocytes/M phi from tuberculin-positive healthy subjects or patients with tuberculosis showed higher TNF-alpha- and IL-6-producing activities than those from tuberculin-negative healthy subjects. The number of TNF-alpha- and IL-6-secreting cells in either lipopolysaccharide- or muramyl dipeptide-stimulated mononuclear cells from tuberculin-positive healthy subjects and patients was significantly higher than that in cells from the tuberculin-negative healthy subjects.

Adult

[Influence of cefodizime on intestinal bacterial flora].

Effects of cefodizime (CDZM), a new injectable cephem antibiotic, on the intestinal bacterial flora were studied in tetra-contaminated mice and in pediatric patients. CDZM was intramuscularly administered at a dose of 100 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organisms: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. For 3 species except E. faecalis, bacterial populations in feces were markedly reduced after the start of the treatment. Subjects in the pediatric study were 5 children with bacterial infections (4 boys and 1 girl) at ages from 7 months to 9 years 6 months and with their body weights ranging from 7.6 kg to 51.1 kg. CDZM was intravenously administered at a dose of 9.7 mg/kg to 23.0 mg/kg 4 times a day for 5 to 15 days. Although some variations in the fecal bacterial flora were noticed among these subjects during the treatment, populations of main aerobes and anaerobes such as Enterobacteriaceae, Enterococcus, Bacteroides, Bifidobacterium and Eubacterium decreased markedly in most cases. Glucose non-fermenting Gram-negative rods and fungi tended to increase during or after the administration of CDZM, and they were the most predominant species in some cases. Although these changes tended to return to predosing states after the cessation of the treatment with CDZM, attention must be paid to possible occurrences of diarrhea, superinfection or bleeding tendency when treatment with the drug is continued for long periods of time. Fecal concentrations of CDZM considered to be closely related to the changes of the intestinal bacterial flora showed pretty high values in all cases.

Animals

[The influence of cefpirome on intestinal bacterial flora].

Cefpirome (CPR, HR810), a new parenteral cephalosporin antibiotic, was studied for its effect on the intestinal bacterial flora in pediatric patients. The subjects were children admitted for infections (6 males and 3 females, 1 month to 5 years 1 month old, weighted 3.94 to 21.0 kg). CPR was intravenously administered at a dose between 19.0 to 40.0 mg/kg, 3 to 4 doses daily over 6 to 12 days. The feces from these children were collected before, during, and after administration, and bacteria were identified and counted. CPR concentration, beta-lactamase activity, and Clostridium difficile D-1 antigen were also assayed. Bacterial flora changes in feces during CPR administration showed some variance, but generally 5 cases out of the 9 showed a significant decrease in Enterobacteriaceae and Enterococcus faecalis among aerobic bacteria. The other 4 cases showed some transient decrease, but no significant change was observed. No significant changes were recognized for Enterococcus avium and Enterococcus faecium, and the total aerobic bacterial count decreased in a transient manner in only one patient. Regarding anaerobic bacteria, Bifidobacterium and Eubactrium revealed a significant decrease, a transient decrease or no change from case to case. Bacteroides showed little change in count. Consequently, the total anaerobic bacteria count did not reveal a large change aside from 1 case in which Bacteroides was not detected before administration and a significant decrease of other bacteria was noted. In no case, glucose nonfermentative Gram-negative bacilli or fungi were found dominant. Although C. difficile and C. difficile D-1 antigen were detected in 3 and 4 cases, respectively, there was no exact relationship between the number of C. difficile and the characteristics of the feces. CPR was detected in fecal samples from 6 cases during administration with concentrations ranging between 1.20 to 22.4 micrograms/g. High values of CPR tended to be found in specimens with low beta-lactamase activity in the feces. When drug sensitivities of the bacteria isolated from feces before and after administration were compared, higher levels of resistance were found in some bacteria such as Enterococci and Bacteroides during or after administration than before administration. The above results suggest that CPR is a drug with a relatively small influence on the intestinal bacterial flora in children, but a particular attention is required for diarrhea and microbial replacement during a continuous, long-term administration of the drug.

Bacteria