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Biomedical subjects

S Nakai

Publications and source records attributed to S Nakai.

At least 145 records · Page 8Linked to original sources

Role of adenosine in dialysis-induced hypotension.

First, this investigation showed that plasma levels of inosine, hypoxanthine, and xanthine, which are metabolites of adenosine, rose sharply when blood pressure dropped suddenly along with symptoms during a hemodialysis session (sudden hypotension), but not when it decreased gradually with eventual symptoms (gradual hypotension). Because adenosine has an action to dilate vessels, this result indicates the possibility that the increased release of adenosine would be a cause of sudden hypotension. Second, it was found that the frequency of sudden hypotension decreases with the administration of caffeine, which is an adenosine-receptor antagonist, whereas the frequency of gradual hypotension did not change. This result supports the above-mentioned hypothesis that adenosine may well be a mediator of sudden hypotension, but not of gradual hypotension. Third, our investigation demonstrated no significant differences in plasma norepinephrine level, in plasma renin activity, or in mean blood pressure between the hemodialysis session in which caffeine was administered and the session in which a placebo was given. These findings suggest that the effect of caffeine administration to prevent sudden hypotension is not mediated by the stimulation of the sympathetic nervous system or activation of the renin-angiotensin system, but by the adenosine-receptor antagonism.

Adenosine↗

Phenotypic expressions of type I, III, IV, V, and VI collagens in patients with diabetic nephropathy: immunohistochemical comparison between HD and non-HD patients.

Molecular organization of extracellular matrix (ECM) in the kidney may change as impairment of renal function progresses. The present immunohistochemical study of the kidney was designed to compare localization of type I, III, IV, V, and VI collagens between "Group A" (13 patients on maintenance hemodialysis due to diabetic nephropathy) and "Group B" (13 patients with diabetic nephropathy and massive proteinuria whose serum creatinine levels were 1.3 +/- 0.5 mg/dl, mean +/- SD). Nodular scleroses that were commonly observed both in Group A (87.8 +/- 10.1%) and B (80.5 +/- 17.0%) were stained in a very similar way with antibodies against collagen types IV, V, and VI. On the contrary, thickened Bowman's capsules that were observed exclusively in Group A (80.7 +/- 10.4% in Group A versus 5.7 +/- 6.2% in Group B) were stained intensely with antibodies against collagen types I and III. Normal and expanded peritubular interstitium from every group was stained with all of the above antibodies in an identical manner. Taken together, these results indicated a close relationship between severe impairment of residual renal function and a high incidence of thickened Bowman's capsule rich in type I and III collagens.

Aged↗

[Clinical efficacy of arbekacin in deep MRSA infection. Including follow-up study after the termination of chemotherapy].

We analyzed the efficacy of arbekacin (ABK) using monotherapy or combined therapy on deep MRSA infection to find the most adequate usage of the drug. We also followed-up the isolation incidence of MRSA after the end of chemotherapy. The results are summarized as follows: 1. Clinical efficacy of ABK on 29 pneumonia and 3 septicemia due to MRSA was 42.9% in ABK monotherapy (9 patients), 62.5% in combined therapy with ABK and minocycline (9 patients), 100% with ABK and imipenem/cilastatin (IPM/CS) (7 patients), and 100% with ABK and other drugs (7 patients). 2. As for microbiological efficacy, combined therapy with ABK and IPM/CS or other drug was superior to other methods. Among patients from whom two or more species of bacteria were isolated, causative bacteria persisted in many cases, and some replacements occurred. 3. Kidney functions deteriorated in two patients that underwent monotherapy or combined therapy with ABK and IPM/CS, but they recovered when therapy was completed the completion. 4. In the three month follow-up study after ABK therapy, we found four cases of renewed infections after disappearance of MRSA. When just decreases in the number of MRSA resulted upon the chemotherapy, the relapse occurred in all cases. 5. Above results indicate that ABK is effective in MRSA infection, and combined therapy with beta-lactams is superior to other methods in serious MRSA infections. We also suggest that chemotherapy should be continued until the complete disappearance of MRSA is achieved.

Adult↗

[Interleukin-1 in cancer therapy].

The therapeutic potentials of interleukin-1 (IL-1) in the cancer therapy are supposed to be; 1) anti-tumor activity, 2) immunostimulating activity, and 3) hematopoietic activity. We observed that IL-1 beta revealed a directly cytostatic activity to certain tumor cells in vitro. Intratumoral or subcutaneous injection of IL-1 beta caused a complete regression and lifespan elongation of tumor-bearing mice by augmenting of the anti-tumor effects mediated by host immune responses indirectly. We have observed IL-1 beta to accelerate the recovery of the numbers of granulocytes and platelets by inducing the production of colony stimulating factors, and by stimulating the hemopoietic progenitor cells. In the phase II clinical study, IL-1 beta was proved to be effective against cutaneous T cell lymphoma (CTCL). In the hematopoietic stimulating activity of IL-1 beta, it was reported in many clinical cases that IL-1 beta accelerated the recovery of the numbers of granulocytes and platelets in myelosuppressed patients.

Animals↗

[DNA heterogeneity in oral cavity and hypopharyngeal carcinoma].

The study was carried out on 18 cases of oral cavity carcinoma and 12 cases of hypopharyngeal carcinoma to assess the degree of intratumoral heterogeneity and the relation to tumor size, lymph metastasis and histological type. In oral cavity carcinoma, 6 cases (33%) were aneuploid, while in hypopharyngeal carcinoma all were aneuploid. DNA heterogeneity was identified in 4 cases (22%) in oral cavity carcinoma, end in 6 cases (50%) of hypopharyngeal carcinoma. No correlation was found between DNA heterogeneity and tumor size, lymph metastasis and histological type. However, even early carcinomas have intratumoral DNA heterogeneity. It was supposed that the result which hypopharyngeal carcinoma had higher degree of aneuploid and DNA heterogeneity comparing with oral cavity carcinoma supported that hypopharyngeal carcinoma had higher clinical malignancy from the aspect of proliferative movement. The data indicate that it is impossible to analyze correct DNA content by only one specimen and it is important to investigate intratumoral DNA heterogeneity to research the mechanism of multiplicity and clinical malignancy of carcinoma.

Adult↗

Vesnarinone inhibits production of HIV-1 in cultured cells.

Vesnarinone, a synthetic oral cardiotonic agent that has been used for treatment of patients with congestive heart failure, was found to inhibit replication of HIV-1 in a peripheral blood lymphocytes model and in chronically infected macrophages at clinically achieved concentrations. Vesnarinone has no direct inhibitory activity against the reverse transcriptase of HIV-1, syncytium formation in short term assays, or retroviral protease. In addition, vesnarinone inhibits production of TNF-alpha and IL-6 by human peripheral blood mononucleated cells stimulated with LPS. These observations suggest that vesnarinone may be therapeutically useful in patients infected with HIV-1.

Antiviral Agents↗

Production and purification of Fab' fragments from chicken egg yolk immunoglobulin Y (IgY).

Methods were described for the production of Fab and Fab' fragments from chicken egg yolk IgY also referred to as IgG by papain and pepsin digestion respectively. Pepsin digestion was found to be suitable for the large scale preparation and purification of Fab'. Optimum yield of Fab' was obtained after peptic digestion of IgY at pH 4.2 for 9 h at low NaCl concentration. This condition led to the complete digestion of pFc' fragment leaving only the Fab' fragment. By combination of ultrafiltration and anion exchange, and conditions which allowed binding of the small amount of contaminants in the digest to the anion exchange column, pure Fab' fragments were easily obtained in the eluent. The advantage of this approach is that a small column could be used to purify large amount of protein, therefore, improving the efficiency of purification. The Fab and Fab' fragments appeared to be similar on the basis of their molecular weights as determined by SDS-PAGE, reaction of identity in immunodiffusion assay and similar antigen binding activities as shown by ELISA.

Animals↗

Comparison of four purification methods for the production of immunoglobulins from eggs laid by hens immunized with an enterotoxigenic E. coli strain.

The importance of eggs as a source of specific antibodies is well recognized. Egg yolk contains 8-20 mg of immunoglobulins (IgY) per ml. However, the major problem in isolation is removal of lipids which are present in high concentrations. A method had been developed by employing water dilution to separate the yolk plasma proteins from the granules and lipids. Further purification of IgY from plasma proteins was achieved by a protocol involving salt precipitation and ultrafiltration. The water dilution method (WD) was compared with three other methods, namely, polyethylene glycol (PEG), dextran sulphate (DS) and xanthan gum (Xan) in terms of yield, purity, ease of use, potential scaling up and immunoactivity of IgY. The WD method gave the highest yield, followed by DS, Xan and PEG methods in that order. 9.8 mg IgY/ml egg yolk was routinely obtained from the WD method compared to 4.9 mg IgY/ml egg yolk with the popular PEG method with purities of 94% and 89% respectively. Purification methods had no adverse effect on the immunoactivities of IgY. WD was also found superior in terms of ease of use and large scale production of IgY. WD method therefore provides a simple, rapid and efficient means of purifying IgY with high activity.

Animals↗

Treatment effect of a traditional Chinese medicine, ren-shen-yang-rong-tang (Japanese name: ninjin-youei-to), on autoimmune MRL/MP-lpr/lpr mice.

MRL/Mp-lpr/lpr (MRL/lpr) mice were treated with a traditional Chinese herbal medicine, Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT) intraperitoneally (i.p.) every 3 days or per os (p.o.) 6 times/week from before the onset of autoimmune disease (6 weeks of age). Fifty percent survival time was found in placebo-controlled male and female mice of 28 and 22 weeks of age, respectively. NYT-treatment markedly prolonged the survival time of MRL/lpr mice. That is, 50% survival time was 43 weeks in the i.p.-treated male mice and 30 weeks of age in the p.o.-treated female mice. Further, NYT-treatment significantly reduced occurrence of thymic atrophy and prevented the anomalous accumulation of B220+ T-cells in lymph node and spleen, both of which are characteristic in MRL/lpr mice. Moreover, grades of proteinuria were significantly reduced in both the i.p.- and p.o.-treated groups compared with the control groups. Such clinical benefit and increased survival time were interestingly not associated with the decrease in the level of autoantibodies.

Animals↗

Role of B-lymphocytes in the immunopharmacological effects of a traditional Chinese medicine, xiao-chai-hu-tang (shosaiko-to).

We previously reported that a traditional Chinese medicine, Xiao-chai-hu-tang (Japanese name: Shosaiko-to), induced interferon (IFN) activity in the serum of mice after intraperitoneal (i.p.) administration. In the present study in which murine spleen cells were cultured in vitro with Shosaiko-to, B-cells isolated by anti-immunoglobulin-coated plates were confirmed to generate IFN in response to Shosaiko-to stimulation. IFN activity was induced in the serum after i.p. administration of Glycyrrhizae radix, Scutellariae radix, Bupleuri radix and Pinelliae tuber which are included in Shosaiko-to as its constituent. Such an IFN-inducing activity was confirmed to exist in methanol-insoluble fractions of these extracts derived from Shosaiko-to and these constituents but not in methanol-soluble fractions. These four extracts as well as Shosaiko-to, induced interleukin 6 (IL-6) in the serum after the administration. In in vitro stimulation of spleen cells, Shosaiko-to and extracts of Glycyrrhizae radix, Bupleuri radix and Pinelliae tuber showed mitogenic activity, but an extract of Scutellariae radix with in vivo IFN-inducing activity did not. B-cells appear to participate in the immunopharmacological effects of Shosaiko-to through mitogenic activity, IFN induction and the effect of IL-6.

Animals↗

Comparative studies of phosvitin from chicken and salmon egg yolk.

1. A method developed for the isolation of phosvitin from chicken egg yolk was successfully applied to the isolation of phosvitin from salmon eggs. 2. Salmon roe phosvitin is smaller in molecular size than chicken egg phosvitin. 3. Circular dichroism spectra of all phosvitins investigated displayed good similarities with spectra showing characteristics of unordered and beta-sheet secondary structure. 4. The main component in the Fourier transform infrared spectra of chicken egg phosvitin is indicative of unordered conformation, whereas the Fourier infrared data of the salmon egg phosvitin are consistent with more of beta-sheet structure compared to the chicken egg phosvitin.

Amino Acids↗

Recent advances in structure and function of food proteins: QSAR approach.

QSAR (quantitative structure-activity relationship), widely used in chemistry with hydrophobic, electronic, and steric parameters as structural factors, was found to be appropriate for use with food proteins, despite the difficulty, due to the complexity in macromolecular structure, in defining the steric terms. Emulsifying ability was closely related to hydrophobicity, and incorporation of solubility to hydrophobicity as factors improved the R2 of regression analysis. Foaming activity required both hydrophobicity and other factors pertaining to the adsorption of proteins at the interface in order to obtain adequate foam lamella strength. Hydrophobicity as well as other factors relating to the intermolecular interactions, for example, Ca and SH are involved in thermally induced gelation. For breadmaking, although no extensive QSAR work had been carried out, the important function of high molecular glutenin subunits was confirmed, and, notably, the critical function of hydrophobicity in breadmaking also was demonstrated. PLS (partial least-squares regression) and neural networks classify more correctly than other multivariate techniques, thereby yielding higher r2 values in modeling and prediction. However, multiple regression analysis and PCR (principal component regression) also were found to be effective for modeling because the information useful in elucidating the mechanism of protein function could be readily obtained. A characteristic property of unsupervised learning techniques, especially PCS (principal component similarity analysis), in identifying influential factors in the function mechanisms was demonstrated.

Bread↗

Responses of plasma vasoactive intestinal polypeptide to methacholine and exercise loading in children and adolescents with bronchial asthma.

Responses of plasma vasoactive intestinal polypeptide (VIP) to methacholine inhalation and to exercise loading were studied in asthmatic patients to clarify a significant role of the peptide. The mean of basal VIP in asthmatics was not significantly different from the normals. The levels were increased after FEV (1.0) (forced expiratory volume in a second) decreased to 80% of the baseline following methacholine inhalation and were returned to values similar to the baseline when FEV (1.0) recovered to 100%. Thirty minutes after the exercise, mean VIP was significantly lower in patients with the lowest FEV (1.0). These results suggest that VIPergic system contributes, at least partly, to relax constricted bronchioles in some patients with bronchial asthma.

Adolescent↗

Purification and characterization of recombinant human macrophage colony-stimulating factor expressed in Chinese hamster ovary cells.

We expressed human macrophage colony-stimulating factor (M-CSF) in Chinese hamster ovary (CHO) cells by introducing an expression plasmid coding for a 554-amino-acid M-CSF precursor and dihydrofolate reductase (DHFR) gene, and by amplifying the sequence. A cell line was obtained that secreted approximately 200,000 units/ml after 6 days in culture. The expressed recombinant human M-CSF (rhM-CSF) primarily consisted of two molecular species, a main 80-90 kD M-CSF as a homodimer and a molecular form higher than 150 kD. Purification of a main rhM-CSF gave an apparently homogeneous protein disulfide-bonded from 42-kD subunits, but one of the purified rhM-CSFs was composed of two subunit species with molecular masses of 44 and 42 kD. These purified rhM-CSFs had substantially the same specific activity (1 to 4 x 10(7) units/mg protein). Deglycosylation experiments with the latter rhM-CSF using chemical (trifluoromethanesulfonic acid) and enzymatic methods found a terminal neuraminic acid in addition to N- and O-glycosylation, but the two subunit species did not coalesce into a single molecule.

Amino Acid Sequence↗

[Problems in DNA ploidy analysis using flow cytometry--influences from contaminant mononuclear cells].

The present study was undertaken to examine the influences of excessive contamination by lymphocytes on the flow cytometric analysis of DNA ploidy of head and neck cancers. Although lymphocytes which contaminate test cells can serve as an internal control (2C), an excess of these lymphocytes can mask the aneuploid peak of cancers. This tendency was particularly prevalent in well-differentiated squamous cell carcinoma. In some cases, most of the cells isolated from tumor-positive HE-stained tissue samples were lymphocytes. This is probably because lymphocytes are likely to survive the cell-isolating procedure, whereas keratocytes are likely to be destroyed during it. If samples excessively contaminated by lymphocytes are subjected to flow cytometry, the aneuploid peak of cancer cells is low relative to the 2C peak, possibly causing an erroneous judgment of diploid. Cytofluorometry, in which a smear of test cells is observed directly to quantify the DNA of cancer cells alone, was useful in detecting lymphocyte-masked aneuploid cells.

Carcinoma, Squamous Cell↗