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C Y Ho

Publications and source records attributed to C Y Ho.

At least 37 records · Page 2Linked to original sources

Laryngeal C-fiber afferents are not involved in the apneic response to laryngeal wood smoke in anesthetized rats.

Laryngeal exposure to wood smoke in rats evokes a reflex apnea which is mediated through superior laryngeal afferents (J. Appl. Physiol. 83: 723-730, 1997). To study the role of laryngeal C-fiber afferents in eliciting this response, capsaicin aerosol (0.05 - 0.2 microg/ml) and 5 ml of wood smoke were delivered separately into a functionally isolated larynx of anesthetized Sprague-Dawley rats at a constant flow rate of 1.4 ml/s, while animals breathed spontaneously. Studies were repeated after either an intravenous injection of ruthenium red (2 mg/kg; n = 8), a perineural capsaicin treatment (200 microg/ml for 5 min; n = 8) of the superior laryngeal nerves, or a perineural sham treatment (n = 8); Ruthenium red inhibits the stimulation of afferent C-fiber nerve endings by capsaicin, whereas perineural capsaicin treatment selective blocks the conduction of C-fiber afferents. Either ruthenium red or perineural capsaicin treatment abolished the apneic response to laryngeal capsaicin, but did not significantly affect the apneic response to laryngeal wood smoke. Furthermore, the apneic responses to both types of irritants were not significantly altered by perineural sham treatment, yet were completely eliminated by a subsequent denervation of superior laryngeal nerves. Our results suggest that superior laryngeal C-fiber afferents are not involved in eliciting the reflex apneic response to laryngeal wood smoke in anesthetized rats. It is speculated that this response may result mainly from the stimulation of myelinated afferents, possibly laryngeal irritant receptors.

Aerosols↗

The immunostimulating activities of anti-tumor polysaccharide from K1 capsular (polysaccharide) antigen isolated from Klebsiella pneumoniae.

We have previously shown that K1 capsular polysaccharide antigen (K1CPS) of Klebsiella exhibits anti-tumor activities. In the present study, we examined the effect of K1CPS on cytotoxic effector cells. We found that K1CPS could activate many cytotoxic effector cells including alloreactive cytotoxic T cells and tumor-infiltrating lymphocytes (TILs). Moreover, K1CPS could increase the anti-tumor activity of lymphokine-activated killer (LAK) cells, both in vitro and in vivo. The i.p. injection of K1CPS in low dose could enhance the LAK cytotoxicity and the effect was further potentiated by coculture of LAK cells with K1CPS and low concentration of murine rIL-2 in vitro. The phenotypic characterization revealed that K1CPS might contribute to the increase in CD3+ LAK cell subpopulation by its in vivo priming effect. In addition, the K1CPS-treated LAK cells were able to inhibit the growth of WEHI-164 tumor cells in vivo in Winn-type inhibition assay. Subcutaneous (s.c.) and intraperitoneal (i.p.) adoptive infusion of LAK cells (splenocytes from K1CPS-treated WEHI-164-bearing mice cultured with K1CPS-plus-rIL-2) into WEHI-164 sarcoma-bearing mice could slightly cause regression in terms of tumor diameter, and more significantly in sarcoma weight.

Adjuvants, Immunologic↗

Elevation of plasma interleukin-18 concentration is correlated with disease activity in systemic lupus erythematosus.

BACKGROUND: Previous studies have indicated that the autoimmune phenomenon might be caused by an imbalance of T-helper cell (Th) cytokines. METHODS: We investigated the plasma concentrations of a novel pro-inflammatory Th1 cytokine, interleukin (IL)-18, and its inducer, IL-12, in patients with systemic lupus erythematosus (SLE) and correlated them with the SLE disease activity index (SLEDAI). Plasma IL-18 and IL-12 concentrations of 40 SLE patients and 18 sex- and age-matched control subjects were measured by enzyme-linked immunosorbent assay. RESULTS: Plasma IL-18 and IL-12 concentrations were significantly higher in SLE patients than in control subjects [median (interquartile range): IL-18, 320.0 pg/ml (164.4-475.6 pg/ml) vs 130.1 pg/ml (57.8-202.4 pg/ml), P<0.001; IL-12, 143.3 pg/ml (39.4-247.2 pg/ml) vs. 84.7 pg/ml (29.3-140.1 pg/ml), P<0.001]. Increases in IL-18 concentration correlated positively and significantly with SLEDAI score (r = 0.449, P = 0.004). CONCLUSION: The novel cytokine IL-18 might play a crucial role in triggering the inflammatory processes in SLE.

Adolescent↗

Sodium salicylate-induced apoptosis of human peripheral blood eosinophils is independent of the activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase.

BACKGROUND: It has been shown that the inhibition of eosinophilic apoptosis is an important mechanism for the development of blood and tissue eosinophilia in allergic diseases. Considerable attention has recently been focused on the role played by different intracellular kinase cascades in the control of apoptosis. In the present study, we investigated the effect of sodium salicylate (NaSal), a nonsteroidal anti-inflammatory drug, on mitogen-activated protein kinases (MAPK) and apoptosis of human eosinophils. METHODS: Human blood eosinophils were purified from buffy coat. NaSal-induced apoptosis of eosinophils was assessed by morphological changes and Annexin-V binding assay. Changes of MAPK activity upon treatment with NaSal were measured by kinase activity assay and Western blot. RESULTS: NaSal could induce apoptosis of human blood eosinophils in a dose- and time-dependent manner. It could also activate c-Jun N-terminal kinase (JNK) and p38 MAPK but not extracellular signal-regulated protein kinase (ERK) activity within 1 h. Pretreatment of eosinophils with p38 MAPK and JNK anti-sense (AS) phosphorothioate oligodeoxynucleotides (ODN) or specific p38 MAPK inhibitor SB 203580 did not have any significant effect on NaSal-induced apoptosis. However, ERK AS ODNs could trigger the apoptosis of normal eosinophils. CONCLUSION: There is no direct relationship between the activation of JNK and p38 MAPK pathways and NaSal-induced apoptosis in human peripheral blood eosinophils.

Anti-Inflammatory Agents, Non-Steroidal↗

Prostaglandin E(2) enhances chemical and mechanical sensitivities of pulmonary C fibers in the rat.

It has been recently reported that pulmonary reflex responses to injection or inhalation challenge of capsaicin are enhanced by exogenous Prostaglandin E(2) (PGE(2)). The present study was carried out to determine whether PGE(2) enhances the stimulatory effects of chemical stimulants and lung inflation on vagal pulmonary C fibers, and if so, whether the excitabilities of other types of lung afferents are also augmented by PGE(2). In anesthetized, open-chest rats, administration of PGE(2) (1.5 microgram/kg/min for 2 min) did not significantly change the baseline activity of vagal pulmonary C fibers, but it markedly enhanced the stimulatory effects of both low (0.25 microgram/kg) and high doses (0.5 microgram/kg) of capsaicin on these fibers. Similarly, potentiating effects of PGE(2) were found on the pulmonary C-fiber responses to injections of lactic acid and adenosine, although considerable variability existed in the degrees of potentiation between the different stimulants. Furthermore, PGE(2) infusion also significantly enhanced the C-fiber response to constant-pressure lung inflation (tracheal pressure [Pt] = 30 cm H(2)O). In contrast, PGE(2) did not alter the responses of either slowly adapting pulmonary receptors or rapidly adapting pulmonary receptors to lung inflation. In summary, these results show that the sensitivity of pulmonary C-fiber afferents to both mechanical and chemical stimuli is enhanced by PGE(2), suggesting that endogenous release of this autocoid may play a part in the airway irritation and dyspneic sensation associated with airway inflammation.

Animals↗

Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus.

Previous studies have indicated that the autoimmune phenomenon might be caused by an imbalance of T helper cell (Th) cytokines. We measured the plasma concentrations of three novel proinflammatory cytokines interleukin (IL)-17, IL-18, IL-12 and a key Th2 cytokine IL-4 in patients with systemic lupus erythematosus (SLE) and correlated the ratio of proinflammatory/Th2 cytokines with SLE disease activity index (SLEDAI). Plasma IL-12, IL-17, IL-18 and IL-4 concentrations of 36 SLE patients and 18 sex- and age-matched control subjects were measured by enzyme linked immunosorbent assay. All were significantly higher in SLE patients than control subjects (IL-12, mean+/-s.d. of 166.7+/-84.5 vs 93.5+/-39.2 pg/ml, P<0.001; IL-17, 76.5+/-45.7 vs 37.6+/-35.3 pg/ml, P=0.002; IL-18, 368.7+/-199. 5 vs 141.1+/-47.1 pg/ml, P<0.001; and IL-4, 27.1+/-15.3 vs 17.3+/-7. 2 pg/ml, P<0.05), and IL-18/IL-4 ratio correlated positively and significantly with SLEDAI score (r=0.435, P=0.006). We propose that SLE is characterized by an elevation of both Th1 and Th2 cytokines: the elevation of proinflammatory cytokine IL-12, IL-17 and IL-18 may trigger the inflammatory process in SLE and the elevation of IL-18/IL-4 ratio suggests an imbalance of cytokine profile to mediate the inflammatory response.

Adolescent↗

Hhex and scl function in parallel to regulate early endothelial and blood differentiation in zebrafish.

During embryogenesis, endothelial and blood precursors are hypothesized to arise from a common progenitor, the hemangioblast. Several genes that affect the differentiation of, or are expressed early in, both the endothelial and blood lineages may in fact function at the level of the hemangioblast. For example, the zebrafish cloche mutation disrupts the differentiation of both endothelial and blood cells. The transcription factor gene scl is expressed in both endothelial and blood lineages from an early stage and can regulate their differentiation. Here we report that in zebrafish the homeobox gene hhex (previously called hex) is also expressed in endothelial and blood lineages from an early stage. We find that hhex expression in these lineages is significantly reduced in cloche mutant embryos, indicating that hhex functions downstream of cloche to regulate endothelial and blood differentiation. Ectopic expression of hhex through injection of a DNA construct leads to the premature and ectopic expression of early endothelial and blood differentiation genes such as fli1, flk1 and gata1, indicating that Hhex can positively regulate endothelial and blood differentiation. However, analysis of a hhex deficiency allele shows that hhex is not essential for early endothelial and blood differentiation, suggesting that another gene, perhaps scl, compensates for the absence of Hhex function. Furthermore, we find that hhex and scl can induce each other's expression, suggesting that these two genes cross-regulate each other during early endothelial and blood differentiation. Together, these data provide the initial framework of a pathway that can be used to further integrate the molecular events regulating hemangioblast differentiation.

Animals↗

Inverted papilloma.

BACKGROUND: Inverted papilloma, a benign sinonasal lesion, constitutes 0.5% to 4% of all nasal tumors. Its local aggressiveness, high recurrence rate, association with malignancy or malignant transformation, and tendency toward multicentricity lead most physicians to advocate radical surgery. Nonetheless, conservative surgery is effective for selected patients with limited disease. This study was done to reassess the efficacy of both radical and conservative surgery. METHODS: The records of all patients with the diagnosis of inverted papilloma treated at the Taipei Veterans General Hospital between January 1986 and October 1998 were collected. A minimal follow-up period of 12 months was required for inclusion in the study. Clinical manifestations, radiologic findings, methods of treatment, pathology reports and recurrence rates were all retrospectively reviewed. RESULTS: Sixty patients with an average age at diagnosis of 58 years were studied. The follow-up period ranged from 12 to 195 months, with a mean of 43 months. The most common presenting symptom was unilateral nasal obstruction. The duration of symptoms ranged from one month to 30 years, with a mean of 36 months. The lateral wall and middle meatus were the most commonly involved sites. Bone erosion and intracranial or intraorbital extension were observed in some patients. Medial maxillectomy was the most common surgical treatment, followed by functional endoscopic sinus surgery and the Caldwell-Luc operation. The overall recurrence rate was 23%, with an average interval from initial treatment to recurrence of 42 months (range, 2-93 months). The recurrence rates for the two groups undergoing medial maxillectomy and conservative surgery were 16% and 27%, respectively. CONCLUSIONS: Early diagnosis relies on high suspicion and biopsy. The treatment modality is related to the location and extent of the disease, which is assessed by preoperative imaging studies. Any tumor with extensive involvement of the sinuses or inaccessibility to the endoscope should be treated with traditional medial maxillectomy for best control. The endoscopic technique is good for preoperative biopsy and follow-up.

Adult↗

A role for the extraembryonic yolk syncytial layer in patterning the zebrafish embryo suggested by properties of the hex gene.

Recent studies in mouse suggest that the extraembryonic endoderm has an important role in early embryonic patterning [1]. To analyze whether similar mechanisms operate in other vertebrates, we cloned the zebrafish homologue of Hex, a homeobox gene that is expressed asymmetrically in the mouse visceral endoderm [2]. Early expression of zebrafish hex is restricted to the dorsal portion of the yolk syncytial layer (YSL), an extraembryonic tissue. By the onset of gastrulation, hex is expressed in the entire dorsal half of the YSL, which directly underlies the cells fated to form the neural plate. We show that hex expression is initially regulated by the maternal Wnt pathway and later by a Bmp-mediated pathway. Overexpression experiments of wild-type and chimeric Hex constructs indicate that Hex functions as a transcriptional repressor and its overexpression led to the downregulation of bmp2b and wnt8 expression and the expansion of chordin expression. These findings provide further evidence that the zebrafish YSL is the functional equivalent of the mouse visceral endoderm and that extraembryonic structures may regulate early embryonic patterning in many vertebrates.

Animals↗

Neonatal capsaicin treatment alters immediate ventilatory responses to inhaled wood smoke in rats.

Neonatal capsaicin treatment chronically ablates unmyelinated C fibers, yet also destroys a small amount of myelinated fibers. Inhalation of wood smoke evokes respiratory reflexes resulting from stimulation of both lung C-fiber nerve endings (unmyelinated afferents) and irritant receptors (myelinated afferents). This study investigated the influences of neonatal capsaicin treatment on the immediate ventilatory responses to inhaled wood smoke in adult rats. Inhalation of wood smoke (approximately 6 ml) via a tracheostomy immediately triggered only an augmented inspiration in 16 rats neonatally treated with capsaicin (50 mg/kg, subcutaneous injection). In contrast, inhaled wood smoke evoked a slowing of respiration in 11 neonatal vehicle-treated rats and an augmented inspiration in another five. The inability to exhibit the slowing of respiration and the persistence of the augmented inspiration in capsaicin-treated rats are consistent with our hypothesis that these two reflex responses originate from stimulation of lung vagal C-fiber afferents and irritant receptors, respectively. Since all capsaicin-treated rats responded to smoke with an augmented inspiration, it is further suggested that neonatal capsaicin treatment selectively impairs the reflex functions of C-fiber afferents and well preserves the reflex functions of lung irritant receptors.

Animals↗

Differentiation of a human eosinophilic leukemic cell line, EoL-1: characterization by the expression of cytokine receptors, adhesion molecules, CD95 and eosinophilic cationic protein (ECP).

Purification of enough eosinophils for the study of allergic inflammation is difficult because eosinophils comprise only a small percentage of circulating leucocytes. A human eosinophilic leukemic cell line, EoL-1, has been considered to be an in vitro eosinophilic model. In the present study, the suitability of EoL-1 cells as an eosinophilic model was further investigated. EoL-1 cells were induced to differentiate by dibutyryl cyclic AMP (dbcAMP). The expression of cell surface cytokines (IL-3, IL-5, GM-CSF) receptors, adhesion molecules (CD49d, CD11b), and CD95 (Fas) was investigated by flow cytometry. Expression of eosinophilic cationic protein (ECP) was determined by fluorescence enzyme immunoassay (FEIA) and reverse transcription-polymerase chain reaction (RT-PCR). EoL-1 cells could be differentiated into eosinophilic vacuole-containing cells by dbcAMP. They were found to express cell surface IL-3 and GM-CSF receptors, CD95 and CD49d. Treatment with dbcAMP could induce the expression of CD11b but decrease the expression of CD95. Anti-CD95 antibody could induce their apoptosis. The differentiation of EoL-1 cells was accompanied by increase in release of ECP into the supernatant and total ECP synthesis. Differentiation of EoL-1 cells also up-regulated the expression of mRNA for ECP and its level was parallel to the total amount of ECP synthesis. By virtue of their expression of haematopoietic cytokines receptors, adhesion molecules, CD95, synthesis and release of ECP, EoL-1 cells are suitable as an in vitro eosinophilic model for studying eosinophilic functions.

Antigens, CD↗

Purification, characterization and molecular cloning of trichoanguin, a novel type I ribosome-inactivating protein from the seeds of Trichosanthes anguina.

The seeds of the plant Trichosanthes anguina contain a type I ribosome-inactivating protein (RIP), designated trichoanguin, which was purified to apparent homogeneity by the combined use of ion-exchange chromatographies, i.e. first with DE-52 cellulose and then with CM-52 cellulose. The protein was found to be a glycoprotein with a molecular mass of 35 kDa and a pI of 9.1. It strongly inhibits the protein synthesis of rabbit reticulocyte lysate, with an IC50 of 0.08 nM, but only weakly that of HeLa cells, with an IC50 of 6 microM. Trichoanguin cleaves at the A4324 site of rat 28 S rRNA by its N-glycosidase activity. The cDNA of trichoanguin consists of 1039 nt and encodes an open reading frame coding for a polypeptide of 294 amino acid residues. The first 19 residues of this polypeptide encode a signal peptide sequence and the last 30 residues comprise an extension at its C-terminus. There are four potential glycosylation sites, located at Asn-51, Asn-65, Asn-201 and Asn-226. A comparison of the amino acid sequence of trichoanguin with those of RIPs such as trichosanthin, alpha-momorcharin, ricin A-chain and abrin A-chain reveals 55%, 48%, 36% and 34% identity respectively. Molecular homology modelling of trichoanguin indicates that its tertiary structure closely resembles those of trichosanthin and alpha-momorcharin. The large structural similarities might account for their common biological effects such as an abortifacient, an anti-tumour agent and anti-HIV-1 activities. Trichoanguin contains two cysteine residues, Cys-32 and Cys-155, with the former being likely to be located on the protein surface, which is directly amenable for conjugation with antibodies to form immunoconjugates. It is therefore conceivable that trichoanguin might be a better type I RIP than any other so far examined for the preparation of immunotoxins, with a great potential for application as an effective chemotherapeutic agent for the treatment of cancer.

Amino Acid Sequence↗

Ribotyping of Vibrio parahaemolyticus isolates obtained from food poisoning outbreaks in Taiwan.

Vibrio parahaemolyticus is a prevalent food-borne pathogen in Taiwan, Japan and other Asian countries. This work presents a novel ribotyping method for the molecular epidemiological examination of this pathogen. Genomic DNA was fragmented by HindIII digestion and hybridized with cDNA probe for Escherichia coli 16S and 23S RNA genes. A total of 121 isolates obtained from outbreaks during 1992 and 1994 in Taiwan were characterized by this ribotyping method. Four to seventeen restricted fragments were visualized in these isolates. After hierarchical cluster analysis, these isolates were grouped into thirty different ribotypes. In addition, A3, A7, E3 and F1 were the major ribotypes, consisting of 22.3, 13.2, 9.1, and 8.3% of the isolates, respectively. A, E, F, G and B were the major groups, consisting of 46.2, 14.0, 9.1, 6.7, and 6.7% of the isolates, respectively. The discriminatory ability of this ribotyping method, as determined by Simpson's index of diversity, was 0.93, which closely resembled that of a previously reported pulsed-field gel electrophoresis method.

Bacterial Typing Techniques↗

Activation of pulmonary C fibres by adenosine in anaesthetized rats: role of adenosine A1 receptors.

1. Intravenous administration of adenosine (Ado) to patients can cause dyspnoea, chest discomfort and bronchoconstriction. To assess the role of vagal pulmonary C fibres in evoking these adverse reactions, the effect of Ado on single pulmonary C fibres was studied in anaesthetized and artificially ventilated rats. 2. Right-atrial injection of Ado (320 microg kg-1) activated 68 % (73/107) of pulmonary C fibres; the total number of action potentials during a period of 15 s increased from a baseline of 0.2 +/- 0.1 impulses to a peak of 16.4 +/- 2.6 impulses (P < 0.01, n = 107) after Ado. Inosine, the metabolite of Ado, did not activate any of eleven C fibres tested in six rats. Furthermore, C fibres were activated only by right-atrial and not by left-ventricular injection of the same dose of Ado. 3. Unlike the immediate and transient stimulation of C fibres by capsaicin, the C fibre stimulation by Ado had a latency of 6.5 +/- 0.3 s (range, 3-18 s) and lasted longer. 4. The stimulation of C fibres by Ado was significantly attenuated by pretreatment with aminophylline, a non-selective Ado receptor antagonist, was completely prevented by 1,3-dipropyl-8-cyclopentylxanthine, an Ado A1 receptor antagonist, but was unaffected by 3,7-dimethy-1-propargylxanthine, an A2 receptor antagonist. None of these Ado receptor antagonists prevented capsaicin-induced C fibre stimulation. 5. In conclusion, Ado stimulates pulmonary C fibre terminals through an activation of A1 receptors. The stimulation of pulmonary C fibres may play an important role in Ado-induced adverse respiratory effects.

Action Potentials↗

Ozone enhances excitabilities of pulmonary C fibers to chemical and mechanical stimuli in anesthetized rats.

Acute exposure to ozone (O3) enhances pulmonary chemoreflex response to capsaicin, and an increased sensitivity of bronchopulmonary C-fiber afferent endings may be involved. The present study was aimed at determining the effect of O3 on the responses of pulmonary C fibers to chemical and mechanical stimuli. A total of 31 C fibers were studied in anesthetized, open-chest, and vagotomized rats. During control, right atrial injection of a low dose of capsaicin abruptly evoked a short and mild burst of discharge [0.77 +/- 0.28 impulses (imp)/s, 2-s average]. After acute exposure to O3 (3 parts/million for 30 min), there was no significant change in arterial blood pressure, tracheal pressure, or baseline activity of C fibers. However, the stimulatory effect of the same dose of capsaicin on these fibers was markedly enhanced (6.05 +/- 0.88 impulses/s; P < 0.01) and prolonged immediately after O3 exposure, and returned toward control in 54 +/- 6 min. Similarly, the pulmonary C-fiber response to injection of a low dose of lactic acid was also elevated after O3 exposure. Furthermore, O3 exposure significantly potentiated the C-fiber response to constant-pressure (tracheal pressure = 30 cmH2O) lung inflation (control: 0.19 +/- 0.07 imp/s; after O3: 1.12 +/- 0.26 imp/s; P < 0.01). In summary, these results show that the excitabilities of pulmonary C-fiber afferents to lung inflation and injections of chemical stimulants are markedly potentiated after acute exposure to O3, suggesting a possible involvement of these afferents in the O3-induced changes in breathing pattern and chest discomfort in humans.

Afferent Pathways↗

Effects of electrical stimulation and postmortem storage on changes in titin, nebulin, desmin, troponin-T, and muscle ultrastructure in Bos indicus crossbred cattle.

The effects of electrical stimulation (ES) on degradation of titin, nebulin, desmin, and troponin-T (TN-T) and on structural changes in the longissimus muscle (LM) from Brahman x Simmental (B x S) cattle (Bos indicus cross) were determined. The left side of seven B x S beef carcasses was stimulated (200 V, 20 Hz) within 1 h of death, and the right side was the nonstimulated (NS) control. Myofibrils for SDS-PAGE and samples for transmission electron microscopy were prepared from the LM at 0, 1, 3, 7, 14, and 28 d postmortem (PM). The SDS-PAGE results showed that the T1 band of titin was absent by 7 d in two animals, by 14 d in four animals, and by 28 d in one animal in both NS and ES samples. By SDS-PAGE, intact nebulin was gone by 7 d in two animals and by 14 d in five animals, but in blots, nebulin decreased by 7 d and was absent by 14 d in both NS and ES samples. The desmin band could still be seen as a light band at 28 d in Western blots of both NS and ES samples. A decrease in TN-T and a concomitant increase in the 30-kDa polypeptide were observed in both NS and ES samples. Western blots with a monoclonal antibody to TN-T confirmed that TN-T decreased at similar rates in NS and ES samples but showed that the 30-kDa polypeptide was more heavily labeled in ES samples from 7 to 28 d. Contraction nodes were present in O-d ES samples and were still observed in 28-d ES samples. Narrow, intermediate, and wide I-band fractures were seen earlier and at a greater frequency in ES than in NS samples. Overall, ES had no detectable effect on titin, nebulin, desmin, or TN-T degradation but accelerated the appearance and enhanced the frequency of three types of I-band fractures in the LM from Bos indicus crossbred cattle.

Animals↗

Trace elements burden in geriatric hemodialysis patients: a prospective multicenter collaborative study.

INTRODUCTION: Hemodialysis therapy and the aging process have been reported to interfere with the trace element (TE) status in the body. This multicenter collaborative study on blood levels of TE in geriatric hemodialysis (HD) patients was carried out with an aim to clarify the impact of the aging process and HD therapy on the TE status in such patients. METHODS: One hundred and fifty-one HD patients (65 male, 86 female), all aged over 60 (68.2+/-3.86 y), and 112 elderly controls (58 male, 54 female) with a mean age of 67.5+/-3.03 were enrolled. All patients underwent standard HD for at least 6 months. The artificial kidneys used were hollow-fiber dialyzers of cellulose membranes. Water used for HD was prepared by reverse osmosis. Blood was collected in the morning prior to dialysis and after fasting. Atomic absorption spectrophotometry was applied to measure blood levels of Pb, Cd and Hg as well as plasma levels of Cu, Zn and Al. Data are presented as mean +/- SEM. Student's t-test and linear regression were applied for statistics. RESULTS: Our geriatric chronic HD patients showed a marked elevation of blood Al and decreased plasma Zn concentrations. The blood levels of Cu, Cd, Pb and Hg were within normal limits. The blood concentrations of Al, Cu and Pb were significantly higher in HD patients than in the normal elderly controls, whereas Cd and Hg were similar in both groups, and Zn were lower in HD patients. Plasma Zn value decreased as dialysis duration increased, however there was a reversely linear correlation between plasma Zn and age. CONCLUSIONS: This data reported can be regarded as a starting point and may serve as an insight to further studies on TE imbalances in geriatric and chronic HD populations.

Aged↗

The 58-kDa cellular inhibitor of the double stranded RNA-dependent protein kinase requires the tetratricopeptide repeat 6 and DnaJ motifs to stimulate protein synthesis in vivo.

Double stranded RNA-dependent protein kinase (PKR) is a double stranded RNA-activated, interferon-induced serine-threonine kinase that participates in both the antiviral and antiproliferative properties of interferon. We previously found that influenza virus inhibited PKR function by recruiting or activating a cellular inhibitor termed P58(IPK). The present study was undertaken to complement our earlier analyses, which demonstrated that P58(IPK) efficiently inhibited PKR autophosphorylation and activity in vitro. We now report that P58(IPK) down-regulates PKR and, in turn, stimulates protein synthetic rates inside the cell. Using transfection analysis, we show that P58(IPK) stimulates translation of secreted embryonic alkaline phosphatase reporter gene mRNA. Furthermore, we found that at least two regions of the P58(IPK) molecule were required for PKR inhibitory activity in COS-1 cells: (i) the DnaJ similarity region at the carboxyl terminus (amino acids 391-504); and (ii) the tetratricopeptide repeat 6 (TPR6) domain (amino acids 222-255) located in the middle of the P58(IPK) protein and within the eukaryotic protein synthesis initiation factor 2alpha homology region. P58(IPK) variants lacking either one of these regions were unable to stimulate secreted embryonic alkaline phosphatase protein synthetic rates. Consistent with this data is the observation that the DeltaTPR6 mutant (the P58(IPK) variant lacking the TPR6 motif) failed to block PKR activity in vitro. Based on these data and our earlier in vitro functional and PKR-P58(IPK) binding analyses, a revised model of PKR regulation by P58(IPK) is presented.

Alkaline Phosphatase↗