Treatment of patients with polyarthritis and anti-HTLV-I antibodies with interferon-alpha.
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Biomedical subjects
Publications and source records attributed to K Maeda.
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The effects of hemodialysis on plasma interleukin 8 (IL-8) levels and the expression of IL-8 mRNA in peripheral blood mononuclear cells (PBMC) were studied in uremic patients undergoing maintenance hemodialysis (HD) using regenerated cellulose dialyzers. The plasma IL-8 levels in the patients after HD sessions were significantly higher than before HD. Comparison of the IL-8 mRNA levels obtained from PBMC before and after HD indicated that the expression of IL-8 mRNA was increased by HD. The enhancement of production of IL-8 in PBMC during HD may be responsible for inflammatory complications and impaired host defense in HD patients.
Complement factor D, a complement system serine protease, circulating in vivo as its active form, accumulates in patients with chronic renal failure. The pathophysiological role of this active protease in these patients was examined by studies on activities of excess factor D on 10 synthetic peptide substrates for some usual serine proteases. The most sensitive of these substrates to factor D was Boc-Gln-Ala-Arg-MCA, which is used as a substrate for trypsin. The proteolytic activity of factor D (2.17 unit/mg/h) on this substrate was estimated to be 10(-5)-fold that of trypsin (2.18 x 10(5) unit/mg/h). The activities of factor D on other synthetic substrates were lower. Thus the proteolytic activity of factor D is considered to be very specific for its natural substrate, complement factor B bound with C3b, even when it is highly accumulated in vivo. The inhibitory effects of some serine protease inhibitors used clinically (nafamostat mesilate, sepinostat mesilate, camostat mesilate and gabexate mesilate) on the proteolytic activity of factor D on its natural substrate, factor B, were also investigated. Of these synthetic compounds, nafamostat mesilate was the most effective inhibitor (ID50:25 microM) of the activity of factor D on factor B.
We developed a new urea kinetic method for simultaneous determination of the Kt/V and protein catabolic rate (PCR) only from blood urea nitrogen (BUN) concentrations before and after a single dialysis session. Using this method, the parameters were calculated within 1.5 s even when a hand-held computer with a low central processing capacity is used. The total amount of urea eliminated during three dialysis sessions in 1 week is assumed to be equal to urea volume (Gw) generated over a 1-week period (Tw): [formula: see text]. Here, G is the generation rate, K is the dialyzer urea clearance, T is the dialysis time and C1, C2 and C3 are BUN during the respective dialysis session. If this equation and the equation expressing the urea kinetics during a single dialysis session are solved together, we have a solution for Kt/V and G. The thus-obtained Kt/V and G are corrected using the change in body weight. The corrected Kt/V showed a good correspondence with the parameter calculated with the classical method, and the midweek PCR derived from G determined by the present method being equivalent to the PCR averaged for a 1-week period determined by the classical methods.
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beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis (HAA), a complication of long-term hemodialysis. However, the pathological role of beta 2M in HAA remains to be determined. Recently, we demonstrated that beta 2M in the amyloid deposits of HAA is modified with advanced glycation end products (AGEs) of the Maillard reaction. Since AGEs have been implicated in tissue damage associated with diabetic complications and aging, we investigated the possible involvement of AGE-modified beta 2M (AGE-beta 2M) in the pathogenesis of HAA. AGE- and normal-beta 2M were purified from urine of long-term hemodialysis patients. AGE-beta 2M enhanced directed migration (chemotaxis) and random cell migration (chemokinesis) of human monocytes in a dose-dependent manner. However, normal-beta 2M did not enhance any migratory activity. AGE-beta 2M, but not normal-beta 2M, increased the secretion of TNF-alpha and IL-1 beta from macrophages. Similar effects were also induced by in vitro prepared AGE-beta 2M (normal-beta 2M incubated with glucose in vitro for 30 d). When TNF-alpha or IL-1 beta was added to cultured human synovial cells in an amount equivalent to that secreted from macrophages in the presence of AGE-beta 2M, a significant increase in the synthesis of collagenase and morphological changes in cell shape were observed. These findings suggested that AGE-beta 2M, a major component in amyloid deposits, participates in the pathogenesis of HAA as foci where monocyte/macrophage accumulate and initiate an inflammatory response that leads to bone/joint destruction.
Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of vascular cell injury in Takayasu's arteritis. To clarify the immunological mechanisms involved, we examined the expression of a cytolytic factor, perforin in infiltrating cells of aortic tissue samples from seven patients with Takayasu's arteritis. We also examined the expression of a 65-kD heat-shock protein (HSP-65), human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 in the aortic tissue. Immunohistochemical studies showed that the infiltrating cells mainly consisted of gamma delta T lymphocytes, natural killer cells, macrophages, cytotoxic T lymphocytes and T helper cells, and that perforin was expressed in gamma delta T lymphocytes, natural killer cells, and cytotoxic T lymphocytes. In situ hybridization analysis also revealed expression of perforin mRNA in the infiltrating cells. Immunoelectron microscopic studies demonstrated that the infiltrating cells released massive amounts of perforin directly onto the surface of arterial vascular cells. We also found that expression of HSP-65, human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 was strongly induced in the aortic tissue and might facilitate the recognition, adhesion and cytotoxicity of the infiltrating killer lymphocytes. These findings provide the first direct evidence that the infiltrating cells in the aortic tissue mainly consist of killer cells, and strongly suggest that these killer cells, especially gamma delta T lymphocytes, may recognize HSP-65 and play a critical role in the vascular cell injury of Takayasu's arteritis by releasing perforin.
The present study examined which subtype of adrenergic receptor in the paraventricular nucleus (PVN) has a role in regulating pulsatile LH secretion and whether CRH mediates the effect of norepinephrine (NE) injection into the PVN on pulsatile LH secretion in ovariectomized (OVX) and ovariectomized estradiol (E2)-treated (OVX + E2) rats. All animals were OVX, and some were sc implanted with Silastic capsules containing E2 dissolved in peanut oil. One week after ovariectomy and E2 implantation, guide cannulae for injection of agent and alpha-helical CRF-(9-41) (alpha-hel CRF), an antagonist of CRH, were stereotaxically implanted into the PVN and third ventricle, respectively. Animals were bled for 3 h at 6-min intervals through an atrial cannula immediately after PVN injection of NE or various adrenergic receptor agonists (phenylephrine, an alpha 1-adrenergic receptor agonist; clonidine, an alpha 2-agonist; and isoproterenol, a beta-agonist). Some of the animals were injected with alpha-hel CRF 5 min before NE injection. NE and both alpha-receptor agonists inhibited pulsatile LH secretion throughout the 3-h sampling period in OVX + E2 rats and significantly reduced the mean plasma LH levels and the LH pulse frequency. On the other hand, LH secretion was inhibited transiently for the first 1-2 h by an injection of NE or an alpha 2-receptor agonist into the PVN in OVX rats, resulting in a significant decrease only in mean plasma LH levels in the NE-injected group. Injection of a beta-agonist did not affect pulsatile LH secretion in either OVX or OVX + E2 animals. Intracerebroventricular injection of alpha-hel CRF before PVN injection of NE completely blocked the NE-induced suppression of pulsatile LH secretion in OVX+E2 rats. These results suggest that 1) the noradrenergic system projecting to the PVN suppresses pulsatile LH secretion via the activation of alpha-adrenergic receptors; 2) this inhibition is mediated by CRH release; and 3) estrogen enhances this suppression.
The roles of the adrenergic projection to the paraventricular nucleus (PVN) and of central CRH in the suppression of pulsatile LH secretion during 48-h fasting were examined in ovariectomized estradiol (E2)-treated rats. The animals were ovariectomized and immediately implanted with Silastic tubing containing E2. One week after ovariectomy and E2 implantation, the animals were implanted stereotaxically with a guide cannula for microinjection into the PVN or intracerebroventricular (icv) injection. One week later, some of the animals were deprived of food for 48 h. The unfasted controls were provided with food ad libitum. At this point, blood samples were collected every 6 min for 3 h. Animals received an injection of 50 micrograms alpha-methyl-p-tyrosine (AMPT), a catecholamine synthesis inhibitor, into the PVN 3 h before the sampling started or an icv injection of 26 nmol alpha-helical CRF-(9-41), a CRH antagonist, after the first hour of blood sampling; control animals were given the vehicle at the equivalent time. The fasted animals injected with AMPT showed a significantly higher mean LH concentration and LH pulse frequency over the 3-h sampling period compared with the vehicle-injected controls. Treatment with AMPT had no significant effect on LH secretion in unfasted animals. The icv injection of alpha-helical CRF-(9-41) reinstated the suppressed LH release in fasted rats, but had no significant effect in unfasted animals. These results suggest that the adrenergic projection to the PVN and central CRH are involved in the suppression of pulsatile LH release during food deprivation. The possibility that fasting activates an ascending adrenergic projection that stimulates CRH release and thus suppresses pulsatile LH secretion is discussed.
The feedback sites of estrogen within the hypothalamus and lower brain stem involved in the suppression of pulsatile LH secretion during 48-h fasting were examined in ovariectomized rats with local estradiol (E2) implants. The animals were ovariectomized and immediately implanted stereotaxically with stainless steel cannula containing crystal E2 diluted 10 times with crystal cholesterol into the medial preoptic area, paraventricular nucleus (PVN), arcuate nucleus (ARC), locus ceruleus, or A1 or A2 region of the brain. Five days later, animals were deprived of food for 48 h, and blood samples were collected every 6 min for 3 h. Animals were immediately refed for 45 h and bled again as described above. Changes in the mean LH concentrations over the 3-h sampling period and the frequency and amplitude of LH pulses were determined by calculating the differences in these parameters between the first and second blood samplings in each animal. Fasting significantly lowered mean LH concentrations in animals implanted with E2 in the A2. The more potent suppression of pulsatile LH release during fasting was found in rats with E2 implants in the PVN: the mean LH concentrations and LH pulse frequency were significantly reduced by fasting in this group. In the animals with E2 implants in the medial preoptic area, ARC, locus ceruleus, or A1, 48-h fasting did not induce any significant changes in LH pulse parameters compared to those in cholesterol-implanted controls. A decrease in LH pulse amplitude was apparent in refed rats as well as fasted animals only when E2 was implanted in the ARC. These results suggest that the feedback action of estrogen at the PVN and/or A2 is required for fasting-induced suppression of pulsatile LH release, as opposed to the so-called negative feedback action of estrogen, which tonically suppresses LH release in nonfasting rats.
The partial base sequences of 18S and 26S rRNAs of strains of Williopsis and Saturnospora species were analyzed. In the three regions partially sequenced, the higher base differences were observed in the strains examined of the three species, W. californica, W. mucosa, and W. pratensis, compared with those of W. saturnus var. saturnus (type species of genus Williopsis), W. beijerinckii, W. mrakii, W. saturnus var. subsufficiens, W. suaveolens, P. membranaefaciens (type species of genus Pichia), C. matritensis (type species of genus Citeromyces), and S'spora dispora (type species of genus Saturnospora): the percent similarities were 52-82 in positions 493-622, 130 bases, of 26S rRNA, and the number of base differences was 28-6 in positions 1611-1835, 225 bases, of 26S rRNA, and the number of base differences was 25-4 in positions 1451-1618, 168 bases, of 18S rRNA. In the 18S rRNA partial base sequencings, W. mucosa had an identical base sequence with P. anomala (identical to H. anomala, type species of genus Hansenula). Based on the sequence data obtained, the taxonomic positions of the three Williopsis species mentioned above are discussed. The genus Zygowilliopsis Kudriavzev was postulated to be retained and emended, and a new genus, Komagataea was proposed for W. pratensis with a new combination, Komagataea pratensis.
The twenty-seven strains of the hat-shaped ascospore-forming, nitrate-assimilating species, formerly classified in the genus Hansenula, of the genus Pichia were examined for their 18S and 26S rRNA partial base sequencings. All the strains examined were separate phylogenetically from the type strain of P. membranaefaciens (type species of genus Pichia). Based on the sequence data obtained [by number of base differences (five or more) with P. anomala and base sequences on fingerprint segment] in the 18S rRNA partial base sequences, these species were divided into seven groups. Group I, including P. anomala (identical to H. anomala, type species of genus Hansenula), P. canadensis, P. muscicola, P. silvicola, P. subpelliculosa, P. americana, P. bimundalis, P. ciferrii, P. syndowiorum, P. bispora, and P. fabianii, corresponded to the genus Hansenula Sydow et Sydow. Groups II and III were comprised of P. capsulata and P. holstii, respectively. Group IV included P. angusta, P. minuta var. minuta, P. minuta var. nonfermentans, P. philodendra, P. glucozyma, and P. henricii. Groups V, VI, and VII included P. jadinii, P. petersonii, and P. dryadoides, respectively. The nitrate assimilation-negative species, P. wickerhamii was phylogenetically distant from P. membranaefaciens. The seven groupings are discussed phylogenetically and taxonomically. For Groups IV, II, and III, the three new genera were proposed as Ogataea, Kuraishia, and Nakazawaea, respectively, with the type species, O. minuta (identical to P. minuta), K. capsulata (identical to P. capsulata), and N. holstii (identical to P. holstii).
Eight strains of species of the teleomorphic genus Dekkera (and anamorphic genus Brettanomyces) were examined for their partial base sequences of 18S and 26S rRNAs. In the 26S rRNA partial base sequencings in positions 493-622 (130 bases) of 26S rRNA, D. bruxellensis (type species) (and B. bruxellensis, type species) and D. anomala (and B. anomalus) were related phylogenetically (percent similarities, 73-82). The percent similarity of D. naardenensis and D. custersiana were very low (48-56 and 48-53, respectively). In the 26S rRNA partial base sequencings in positions 1611-1835 (225 bases) of 26S rRNA, D. bruxellensis (and B. bruxellensis) and D. anomala (and B. anomalus) were related phylogenetically (base differences, 8-6). The base differences of D. naardenensis and D. custersiana were 46-38 and 38-27, respectively. In the 18S rRNA partial base sequencings in positions 1451-1618 (168 bases) of 18S rRNA, D. bruxellensis (and B. bruxellensis) and D. anomala (and B. anomalus) were closely related phylogenetically (base difference, one). The base differences of D. naardenensis were three with the above-mentioned two species. In contrast, D. custersiana was distant phylogenetically (base differences, 10-9). The sequence data obtained were discussed taxonomically, especially on setting up a new teleomorphic genus for D. custersiana.
The partial base sequences of 18S and 26S rRNAs of Rhodosporidium fluviale, R. lusitaniae, and Erythrobasidium hasegawianum were analyzed. In the 26S rRNA partial base sequencings, R. fluviale CBS 6568 and R. lusitaniae IGC 4599 and IGC 4641 had 81-82 and 77 percent similarities compared with R. toruloides (type species of genus Rhodosporidium) IFO 0559 and IFO 0880. Erythrobasidium hasegawianum IFO 1058 showed 69-71, 59, 63, and 61 percent similarities with R. toruloides IFO 0559 and IFO 0880, L. scottii (type species of genus Leucosporidium) IFO 1923, R. dacryoidum IFO 1930 and IFO 1931, and Kondoa malvinella IFO 1936, respectively. In the 18S rRNA partial base sequencings, R. fluviale CBS 6568 and R. lusitaniae IGC 4599 and IGC 4641 had zero and two base differences with R. toruloides. Erythrobasidium hasegawianum IFO 1058 showed ten, sixteen, three, and twenty base differences with R. toruloides IFO 0559 and IFO 0880, L. scottii IFO 1923, R. dacryoidum IFO 1930 and IFO 1931, and K. malvinella IFO 1936, respectively. Based on the sequence data obtained, a new genus, Sakaguchia was proposed for R. dacryoidum with a new combination, Sakaguchia dacryoides.
The nucleotide sequence of the 5'-end of feline calicivirus (FCV) Japanese F4 strain genome was determined. This region had 5311 bases and contained a large open reading frame (ORF1) encoding the non-structural proteins. The nucleotide sequence of the ORF1 region was highly conserved as compared with that of FCV F9 strain. When the deduced amino acid sequence of the ORF1 was compared with those of FCV F9 and CFI strains, the sequence was also highly conserved (88.9% and 88.8%, respectively). Functional motifs of the non-structural proteins were common to these strains. There were 2C polypeptide-, 3C cysteine protease- and 3D RNA-dependent RNA polymerase-like regions. The N-terminal region of 2C-like region continued upstream from the region identified by Neill [Virus Res. 17: 145-160]. Furthermore, the presence of 2B-like region was suggested in the upper stream of the 2C-like region, although the function of the region is unknown. When Kyte and Dolittle hydrophobicity profiles of the predicted amino acid sequences of the ORF1s of FCV F4 and F9 were computed and compared, both the profiles had striking similarities. In the region between residues 950-1000, there was a high rate of basic amino acid residues, suggesting that the polypeptide in this region of FCV may have a nucleic acid-binding function.
Two cases of physiologic sinusoidal FHR pattern and one case of pathologic sinusoidal FHR pattern recorded on fetal actocardiograms are reported. The physiologic sinusoidal FHR patterns were recorded during periodic fetal respiratory movements and sucking movements. The physiologic sinusoidal FHR patterns were accompanied and synchronized with periodic fetal movement bursts. The pathologic sinusoidal FHR pattern observed in a case of severe fetal anemia due to massive fetal-to-maternal hemorrhage was not accompanied by any fetal movement bursts. It is suggested that with the use of fetal actocardiogram physiologic sinusoidal FHR pattern can be distinguished from pathologic sinusoidal FHR pattern.
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.