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Biomedical subjects

Kenji Maeda

Publications and source records attributed to Kenji Maeda.

61 records · Page 4Linked to original sources

Platelet GPIIb/IIIa is activated and platelet-leukocyte coaggregates formed in vivo during hemodialysis.

BACKGROUND/AIM: During hemodialysis, platelets and leukocytes are activated and form platelet-leukocyte coaggregates in which GPIIb/IIIa (CD41/CD61) and CD62P (P-selectin) are involved. However, it is still controversial whether platelet activation and platelet-leukocyte coaggregate formation are dependent on the dialyzer membrane material. METHOD: We examined the appearance of activation-dependent antibody on platelets as an index of platelet activation, and the appearance of platelet-specific antigen on leukocytes as an index of platelet-leukocyte coaggregation, during hemodialysis in 7 patients treated using regenerated cellulose (RC) membrane and next using polysulfone (PS) membrane. In order to reduce the influence of factors other than dialyzer membrane material, this study was conducted in a prospective crossover fashion using a pyrogen-free bicarbonate dialysate. Moreover, flow cytometric techniques with whole blood were employed, which reduce artificial cell activation during the cell or plasma separation procedure. The platelet-specific monoclonal antibodies used in this study were anti-CD61, PAC-1 (which recognizes only the conformationally activated GPIIb/IIIa) and anti-CD62P. RESULTS: Changes in the percentage of PAC-1-positive platelets were significantly greater during hemodialysis with RC than with PS. However, changes in the percentage of CD62P-positive platelets were not significantly different between hemodialysis with RC and PS. Changes in the percentage of CD61- or CD62P-positive leukocytes were significantly greater during hemodialysis with RC than with PS. Although changes in percentage of PAC-1-positive platelets did not parallel those of CD62P-positive platelets during hemodialysis, there was a significant positive correlation between the percentage of CD61-positive leukocytes and the percentage of CD62P-positive leukocytes. CONCLUSION: This study, conducted in a prospective crossover fashion using a pyrogen-free bicarbonate dialysate in order to reduce the influence of factors other than the dialyzer membrane material, demonstrated that both the degrees of GPIIb/IIIa activation and platelet-leukocyte coaggregation were greater during hemodialysis with RC than PS.

Adult↗

Which Kt/V is the most valid for assessment of both long mild and short intensive hemodialyses?

It is unclear at present which mathematical modeling Kt/V(urea) is valid for assessment of both long mild hemodialysis (HD) and short intensive HD, the single-pool modeling Kt/V (Kt/Vsp) based on the pre- and postdialysis serum urea concentrations, double-pool modeling Kt/V (Kt/Vdp) based on the predialysis concentration and the estimated postdialysis equilibrated concentration, or Kt/V calculated on the basis of dialyzer urea clearance, HD session duration and urea distribution volume (Kt/Vdl). Thus, the respective Kt/V during a short intensive HD was compared with its counterpart Kt/V during a long mild HD, where the same amount of urea is removed during both HD treatments. It was found that the Kt/Vsp and Kt/Vdl during short intensive HD were significantly greater than the respective Kt/V during the long mild HD. On the other hand, there was no significant difference in the Kt/Vdp between the long mild and short intensive HDs. In conclusion, Kt/Vdp may be more valid for assessment of both long mild and short intensive HDs.

Female↗

Study design, statistical method, and level of evidence in Japanese and American clinical journals.

Clinical articles published in Japanese journals are said to be characterized by poor study design, less sophisticated statistics, and producing few high-grade clinical evidences. Two American and two Japanese medical journals, published in 1990, 1993, 1996, and 1999 were compared to find out the differences regarding study design, statistical methods, and level of clinical evidence of original articles and synthetic studies. There were 1689 original articles in American and 308 in Japanese joumals. Regarding study design, American articles contributed much more to randomized controlled trials/controlled trials/clinical trials (27.9% vs. 14.3%, p=0.001), cohort studies (21.6% vs. 6.2%, p=0.001), and case-control studies (6.5% vs.0.3 %, p=0.000). Among original articles in American and Japanese journals, mean number of statistical methods used were 2.4 and 1.7 per article (p=0.000), respectively. Articles providing high grade clinical evidence (grade Ia, Ib & IIa) were much greater in proportion in American journals than Japanese journals (31.1% vs. 12.7%, p=0.001). The overall picture of Japanese medical articles seems to be improving recently, at least in terms of statistical methods toward more diversified and sophisticated way of use, compared to the previous data.

Data Interpretation, Statistical↗

Genetic characterization of hantaviruses transmitted by the Korean field mouse (Apodemus peninsulae), Far East Russia.

In an epizootiologic survey of 122 rodents captured in Vladivostok, Russia, antibodies positive for hantavirus were found in Apodemus peninsulae (4/70), A. agrarius (1/39), and Clethrionomys rufocanus (1/8). The hantavirus sequences identified in two seropositive A. peninsulae and two patients with hemorrhagic fever with renal syndrome (HFRS) from the Primorye region of Far East Russia were designated as Solovey and Primorye, respectively. The nucleotide sequences of the Solovey, Primorye, and Amur (obtained through GenBank) sequences were closely related (>92% identity). Solovey and Primorye sequences shared 84% nucleotide identity with the prototype Hantaan 76-118. Phylogenetic analysis also indicated a close relationship between Solovey, Primorye, Amur, and other viruses identified in Russia, China, and Korea. Our findings suggest that the Korean field mouse (A. peninsulae) is the reservoir for a hantavirus that causes HFRS over a vast area of east Asia, including Far East Russia.

Animals↗

[New HIV-1 protease inhibitors in development].

Protease inhibitors block the protease enzyme of HIV-1. When new viral particles break off from an infected cell, protease cuts long protein strands into the parts needed to assemble a mature virus. When protease is blocked, the new viral particles cannot mature. Protease inhibitors being tested in humans include Atazanavir, GW433908, L-756,423, Mozenavir(DMP-450), Tipranavir and more. Several firms are trying to develop a new type of protease inhibitor that will be the more favorable pharmacokinetic and resistance profiles compared with currently available drugs. We cannot expect that every one of the drugs listed in this paper will be successfully developed. However, it is likely that significant clinical advancements can be made with those that are proven to be active and safe for patients in need.

Anti-HIV Agents↗

Identification of amino acid residues critical for LD78beta, a variant of human macrophage inflammatory protein-1alpha, binding to CCR5 and inhibition of R5 human immunodeficiency virus type 1 replication.

In an attempt to determine which amino acid(s) of LD78beta, a variant of human macrophage inflammatory protein-1alpha, plays a critical role in the interaction with CCR5, we generated six LD78beta variants with an amino acid substituted to Ala at the NH(2) terminus of LD78beta. There was no significant difference in eliciting Ca(2+) flux and chemotaxis among the variants with the exception of LD78beta(T9A) showing a substantially reduced activity. The comparative order for human immunodeficiency virus type 1 (HIV-1) replication inhibition was: LD78beta(P8A) > LD78beta(D6A) > LD78beta(WT), LD78beta(L3A) > LD78beta(T7A), LD78beta(P2A) > LD78beta(T9A). In binding inhibition assays of LD78beta variants using 2D7 monoclonal antibody and (125)I-labeled macrophage inflammatory protein-1alpha, the comparative order was: LD78beta(P8A), LD78beta(D6A) > LD78beta(WT) > LD78beta(L3A) > LD78beta(T7A) > LD78beta(T9A), LD78betaP2A). The order for CCR5 down-regulation induction was comparable to that for binding inhibition. The present data suggest that Pro-2, Asp-6, Pro-8, and Thr-9 are critical for LD78beta binding to CCR5 and HIV-1 replication inhibition, and that LD78beta binding to CCR5, regardless of affinity, is sufficient for the initial signal transduction of LD78beta, whereas the greater anti-HIV-1 activity requires the greater magnitude of binding. The data also suggest that LD78beta variants with appropriate amino acid substitution(s) such as LD78beta(D6A) and LD78beta(P8A) may represent effective chemokine-based anti-HIV-1 therapeutics while preserving LD78beta-CCR5 interactions.

Amino Acid Sequence↗

An improved method for detecting faecal Vibrio cholerae by PCR of the toxin A gene.

A method for removing inhibitor(s) of the PCR assay for the direct detection of cholera toxin A gene (ctxA) in human faeces is described. Inhibitors of the PCR were removed by centrifugation and the activity of the remaining inhibitors by dilution. Based on these data, a protocol was developed for pre-treatment of stool specimens for PCR assay, and a simple and rapid protocol was constructed for the diagnostic detection of the ctxA genes in stool specimens in combination with single band detection on gel electrophoresis, dot-blot hybridisation and enrichment culture. This protocol was applied to clinical specimens and showed that the PCR method gave 100% agreement with established culture methods for the detection of cholera toxin-producing Vibrio cholerae O1. This protocol was considered to be useful because of its simplicity and the rapidity of diagnosis.

Carrier State↗