Biomedical subjects

Y Gu

Publications and source records attributed to Y Gu.

At least 199 records · Page 11Linked to original sources

PubMed1998

Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes permeable to water and urea, but not to glycerol.

A new member (AQP9) of the aquaporin family was identified from human leukocytes by homology cloning using PCR. A full length clone was obtained by screening human liver cDNA library. AQP9 encodes a 295-amino-acid protein with the amino acid sequence identity with AQP3 (48%), AQP7 (45%), and other aquaporins (approximately 30%), suggesting that AQP3, AQP7, and AQP9 belong to a subfamily of the aquaporin family. Injection of AQP9-cRNA into Xenopus oocytes stimulated the osmotic water permeability 7-folds with a low activation energy (4.2 kcal/mol) which was inhibited by 0.3 mM mercury chloride by 48%. AQP9 also facilitated urea transport 4-folds. However, in contrast to AQP3 and AQP7, AQP9 did not stimulate the glycerol permeability, suggesting a unique permeability character. Northern blot analysis revealed the high expression of 3.5-kb messages in peripheral leukocytes >> liver > lung = spleen, but not in thymus. The possible role of AQP9 in the immunological function of leukocytes is intriguing and the identification of AQP9 with unique permeability profile may expand our understanding of water and small solute transport in the body.

Amino Acid Sequence↗

PubMed1998

[3H]RS79948-197 binding to human, rat, guinea pig and pig alpha2A-, alpha2B- and alpha2C-adrenoceptors. Comparison with MK912, RX821002, rauwolscine and yohimbine.

The Kd values of the recently introduced radioligand [3H]RS79948-197 ((8a R,12aS,13a-S)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-metho xy-12-(ethylsulphonyl)-6H-isoquino[2,1-g][1,6]naphthyridine) were determined for the recombinant human and rat alpha2A-, alpha2B- and alpha2C- as well as guinea pig alpha2B- and alpha2c-adrenoceptors expressed in COS (CV-1 Origin, SV40) cells. In addition, the Kd values were also determined for [3H]RS79948-197 for the guinea pig spleen alpha2A-adrenoceptor and for pig alpha2A-, alpha2B- and alpha2C-adrenoceptors in membranes obtained from kidney and striatum. Available radioligands for alpha2-adrenoceptors, besides [3H]RS79948-197 are the tritiated forms of MK912 ((2S,12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octa hydro-2H-benzo[b]furo[2,3-a]quinazoline)-2,4'-pyrimidin-2'-one), RX821002 (2-methoxy-idazoxan), rauwolscine and yohimbine. In the present article the binding constants of all these substances for the alpha2A-, alpha2B- and alpha2C-adrenoceptor subtypes in human, pig, rat and guinea pig are reviewed. In all species tested MK912 was alpha2C-selective, RX821002 showed a minor alpha2A-selectivity, whereas [3H]RS79948-197 was non-selective among the alpha2-adrenoceptor subtypes, showing high affinity for all three subtypes. Rauwolscine and yohimbine showed relatively low affinities for nmost of the alpha2-adrenoceptor subtypes investigated, the exception being rauwolscine having high affinity for the human and porcine alpha2C-adrenoceptors.

Adrenergic Agents↗

PubMed1998

Interleukin-18 (IFNgamma-inducing factor) induces IL-8 and IL-1beta via TNFalpha production from non-CD14+ human blood mononuclear cells.

IL-18 is synthesized as a precursor molecule without a signal peptide but requires the IL-1beta converting enzyme (ICE, caspase-1) for cleavage into a mature peptide. Human precursor IL-18 was expressed, purified, and cleaved by ICE into a 18-kD mature form. Mature IL-18 induced IL-8, macrophage inflammatory protein-1alpha, and monocyte chemotactic protein-1 in human peripheral blood mononuclear cells in the absence of any co-stimuli. Blocking IL-1 with IL-1 receptor antagonist resulted in a 50% reduction in IL-8. Neutralization of TNF with TNF binding protein resulted in a 66% reduction in IL-1beta, an 80% reduction of IL-8, and an 88% reduction in mean TNFalpha mRNA. In purified CD14+ cells but not CD3+/CD4+, IL-18 induced gene expression and synthesis of IL-8 and IL-1beta. TNFalpha production was induced in the non-CD14+ population and there was no induction of TNFbeta by IL-18. In purified natural killer cells, IL-18 induced IL-8 that was also inhibited by TNF binding protein. IL-18 did not induce antiinflammatory cytokines, IL-1Ra, or IL-10, although IL-18 induction of TNFalpha was inhibited by IL-10. In the presence of IFNgamma, IL-18-induced TNFalpha was enhanced and there was an increase in the mature form of IL-1beta. We conclude that IL-18 possesses proinflammatory properties by direct stimulation of gene expression and synthesis of TNFalpha from CD3+/CD4+ and natural killer cells with subsequent production of IL-1beta and IL-8 from the CD14+ population.

CD3 Complex↗

PubMed1998

Cross-modulation of glycine-activated Cl- channels by protein kinase C and cAMP-dependent protein kinase in the rat.

1. The cross-modulation of glycine responses by cyclic-AMP-dependent protein kinase (PKA) and protein kinase C (PKC) was determined in acutely dissociated trigeminal neurons. 2. Whole-cell glycine-evoked Cl- current (IGly) was recorded using the patch clamp technique. Protein kinases and their inhibitors were intracellularly perfused into the cells. 3. Both PKA and PKC when applied separately potentiated IGly. 4. When PKA and PKC were sequentially applied, PKC could not increase the IGly any further after the glycine responses were enhanced by PKA. 5. In 42% of our cells, IGly increased spontaneously. Endogenous PKA was found to mediate the increase. PKC had no effects on IGly in these cells. 6. The effect of PKA on IGly was studied in PKC-pretreated cells. PKA failed to potentiate IGly in these cells, suggesting that the PKA action also depends on the activity of PKC inside the cells. 7. These results suggest that the PKC action on IGly is conditional upon the modulation of the currents by PKA and vice versa. This cross-regulation of ligand-gated channel activity by protein kinases may play a role in neuronal integration and synaptic plasticity.

Action Potentials↗

PubMed1998

Non-Hodgkin's lymphoma and family history of malignant tumors in a case-control study (United States).

Using data from a case-control study in the United States (the Selected Cancers Study), we examined the relationship between non-Hodgkin's lymphoma (NHL) and family history of different cancers. Cases were 1,511 men aged 31 to 59 years and diagnosed pathologically with non-Hodgkin's lymphoma during 1984-88. Controls were men, frequency-matched to cases by age range and cancer registry (n = 1,910). All study subjects with acquired immunodeficiency syndrome were excluded from analyses. Our results showed that the risk of NHL is associated with a history of lymphoma (odds ratio [OR] = 3.0, 95 percent confidence interval [CI] = 1.7-5.2) and hematologic cancer (OR = 2.0, CI = 1.2-3.4) in first-degree relatives after adjustment for age, ethnic background, and educational level. Further analyses were performed for the subgroups defined by age at diagnosis (younger than 45 years cf 45 years or older). The association of NHL with a family history of lymphoma and hematologic cancer was found primarily among men aged 45 and older (OR = 4.1, CI = 1.9-8.8 for lymphoma and OR = 2.3, CI = 1.3-4.0 for hematologic cancer). The association among men aged 45 and older did not vary by whether or not there were any familial patients diagnosed at the age of 45 or older. No significant associations could be found for a family history of lung cancer, breast cancer, prostate cancer, colon cancer, skin cancer, liver cancer, stomach cancer, brain cancer, thyroid cancer, or myeloma. This study suggests that the familial risk of NHL is influenced primarily by hematolymphoproliferative malignancies rather than other cancers. The familial effects of hematolymphoproliferative malignancies may be stronger for men aged 45 to 59, compared with those aged 31 to 44.

Adult↗

PubMed1998

Induction of apoptosis in proliferating lymphocytes by tricyclic antidepressants.

We have previously found that tricyclic antidepressants (TCAs) induce apoptosis in quiescent human lymphocytes. The aim of the present study was to evaluate if TCAs induce apoptosis in proliferating human lymphocytes and in established blastoid lymphocytes also. The development of conA-induced lymphoblast populations was followed by measuring the CD25 membrane expression. Three TCA compounds were run with the following concentrations: imipramine (10, 20, 30, 40, 60 microM), clomipramine (1, 10, 20, 30, 40 microM) and citalopram (40, 60, 80, 100, 180 microM). They all induced a dose-dependent apoptosis both in continuously transformed, as well as in established lymphoblasts. Preincubation of the TCA up to 48 h did not significantly increase induction of apoptosis. The three drugs tested were found to be potent inducers of apoptosis in proliferating lymphocytes. Furthermore, we found that the apoptotic populations in proliferating and in established blastoid lymphocytes were of fairly the same magnitude than in the corresponding population in TCA-incubated resting lymphocytes. In conclusion, we demonstrate that TCAs induce apoptosis in proliferating lymphocytes, as they do in quiescent lymphocytes. Furthermore, the extent of apoptosis was even more pronounced in TCA-incubated lymphoblasts compared to TCA-treated resting lymphocytes.

Journal Article↗

PubMed1998

Self-reported infectious mononucleosis and 6 cancers: a population-based, case-control study.

A study was undertaken to estimate the magnitude of association between self-reported infectious mononucleosis (IM) and 6 types of cancer, including Hodgkin's disease, non-Hodgkin's lymphoma, nasopharyngeal cancer, nasal cancer, primary liver cancer, and sarcoma. Cases were male, aged 15-39 y in 1968, who lived in 8 cancer registry areas. Controls were men selected by random-digit telephone dialing. Cases included 1511 persons with non-Hodgkin's lymphoma, 343 with Hodgkin's disease, 386 with sarcoma and 168, 113 and 70 with primary liver, nasopharyngeal and nasal cancers, respectively. There were 1910 controls. For the 6 cancers combined, the overall odds ratio for IM occurring < 5 and > or = 5 y of the reference date were 5.40 [95% (Confidence Interval (CI) = 1.61, 18.09] and 1.08 (0.84, 1.40), respectively. Analogous values were 4.59 (1.25, 16.85) and 1.07 (0.78, 1.48) for non-Hodgkin's lymphoma and 7.49 (1.52, 36.92) and 1.35 (0.87, 2.09) for Hodgkin's disease. There was the suggestion of a protective association with IM occurring > or = 5 y before cancer onset for the 4 non-lymphomatous cancers. Strongly positive associations between self-reported IM and 6 types of cancer were observed for IM occurring < 5 y before the onset of cancer. There was a suggestion, which is noted with extreme caution, that IM earlier in life might have had a protective association with the 4 non-lymphomatous cancers.

Adolescent↗

PubMed1998

Accumulation of tau in autophagic vacuoles in chloroquine myopathy.

Long-term administration of chloroquine to rats induces a vacuolar myopathy, which is specifically termed chloroquine myopathy (CM). In CM, tau mRNA levels were transiently upregulated in the early phase, while tau itself slowly accumulated in the late phase. The temporal profiles of tau mRNA levels and its accumulation were very similar to those of beta-amyloid protein precursor (APP) and its carboxyl-terminal fragments, both of which have been known to be degraded in lysosomes. Immunocytochemistry showed that tau progressively accumulated in the rimmed vacuoles exhibiting increased acid phosphatase activities, and immunoelectron microscopy demonstrated that tau was located within autophagic vacuoles. These results suggest that the accumulation of tau in CM is due to defective tau degradation in the lysosomal compartment in the muscle.

Acid Phosphatase↗

PubMed1998

Borrelia burgdorferi escape mutants that survive in the presence of antiserum to the OspA vaccine are killed when complement is also present.

As an initial attempt to investigate the possible role of outer surface protein A (OspA) escape mutants of Borrelia burgdorferi in decreasing the efficacy of the OspA vaccine, mutants of the HB19 strain of B. burgdorferi sensu stricto were selected in vitro from an uncloned, low-passage-number isolate. The antiserum used for selection was obtained from rhesus monkeys that had been given a vaccine of the same formulation and dose, and by the same route of administration, as that given to humans in several trials. All of the mutants selected in liquid medium and subsequently cloned twice in solid medium expressed a single abundant protein of 28 to 34 kDa instead of both OspA and OspB. Depending on the mutant, this protein reacted strongly, weakly, or not detectably with the anti-OspA antibody used for selection. Analysis of the ospAB locus of each of four representatives from these three groups of mutants by PCR with oligonucleotide primers that hybridize to flanking regions of the ospAB operon, and of the corresponding phenotype with monoclonal antibodies that bind to the amino or carboxyl terminus of the OspA or OspB polypeptide, indicated that in all cases a deletion within the operon had occurred. Spirochetes from the four mutant strains chosen for further analysis could be killed in antibody-dependent, complement-mediated killing assays with the selecting anti-OspA antibody, despite their resistance to killing with this antibody in the absence of complement. Complement-mediated killing occurred at an antibody concentration higher than that required to kill wild-type spirochetes. If anti-OspA antibody acts only within the tick, where complement is probably ineffective due to tick-derived decomplementing factors, then OspA escape mutants, if infectious, could seriously diminish the efficacy of OspA vaccines. On the other hand, if the killing of B. burgdorferi with anti-OspA antibody also takes place within the human host, then our results indicate that chimeric/deletion escape mutants will be killed as well.

Antigens, Bacterial↗

PubMed1998

A water channel of the nematode C. elegans and its implications for channel selectivity of MIP proteins.

A genome project focusing on the nematode Caenorhabditis elegans has demonstrated the presence of eight cDNAs belonging to the major intrinsic protein superfamily. We functionally characterized one of these cDNAs named C01G6.1. Injection of C01G6.1 cRNA increased the osmotic water permeability (Pf) of Xenopus oocytes 11-fold and the urea permeability 4.5-fold but failed to increase the glycerol permeability. It has been speculated that the MIP family may be separated into two large subfamilies based on the presence or absence of two segments of extra amino acid residues ( approximately 15 amino acids) at the second and third extracellular loops. Because C01G6.1 (designated AQP-CE1), AQP3, and glycerol facilitator (GlpF) all have these two segments, we replaced the segments of AQP-CE1 with those of AQP3 and GlpF to identify their roles. The functional characteristics of these mutants were principally similar to that of wild-type AQP-CE1, although the values of Pf and urea permeability were decreased by 39-74% and 28-65%, respectively. These results suggest that the two segments of extra amino acid residues may not contribute to channel selectivity or formation of the route for small solutes.

Amino Acid Sequence↗

PubMed1998

Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function.

Novel mutations of the aquaporin-2 (AQP2) gene have been detected in Japanese female siblings with autosomal-recessive nephrogenic diabetes insipidus. The patients were compound heterozygote for point mutations at nucleotide position 374 (C374T) and at position 523 (G523A) in exon 2 of the AQP2 gene, resulting in substitution of methionine for threonine at codon 125 (T125M) and arginine for glycine at codon 175 (G175R). The water permeability (Pf) of oocytes injected with wild-type complementary RNA increased 9.0-fold compared with the Pf of water-injected oocytes, whereas the increases in the Pf of oocytes injected with T125M and G175R complementary RNA were only 1.7-fold and 1.5-fold, respectively. Immunoblot and immunocytochemistry indicated that the plasma membrane expressions of T125M and G175R AQP2 proteins were comparable to that of the wild-type, suggesting that although neither the T125M nor G175R mutation had a significant effect on plasma membrane expression, they both distorted the structure and function of the aqueous pore of AQP2. These results provide evidence that the nephrogenic diabetes insipidus in patients with T125M and G175R mutations is attributable not to the misrouting of AQP2, but to the disrupted water channel function.

Amino Acid Sequence↗

PubMed1998

Developmental expression and regulation of basic fibroblast growth factor and vascular endothelial growth factor in rat decidua and in a decidual cell line.

During pregnancy, the decidua is comprised of two separate tissues located either mesometrially or antimesometrially in the uterus. Trophoblast invasion takes place only in the mesometrial decidua, where extensive angiogenesis, essential for successful implantation, occurs. Both basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been implicated in this phenomenon. The aim of this study was to determine whether the expression of both growth factors is intrinsic to decidua and occurs in the absence of conceptuses, whether their genes are expressed specifically in the mesometrial decidua, the site of angiogenesis, and whether both growth factors are developmentally and hormonally regulated. Decidual tissue was dissected from pseudopregnant rats and levels of both bFGF and VEGF mRNA were examined in mesometrial and antimesometrial decidua by semi-quantitative RT-PCR at different stages of pseudopregnancy. Although induction of decidualization triggered the mRNA expression of bFGF, VEGF mRNA expression remained unchanged. VEGF mRNA level was similar in both antimesometrial and mesometrial decidua, and remained constant throughout pseudopregnancy. In sharp contrast, bFGF mRNA was highly expressed in the mesometrial decidua at a time when extensive angiogenesis takes place in this tissue. Very little signal was observed in the antimesometrial decidua. To examine the regulation of these growth factors, we used a temperature-sensitive decidual cell line developed by transforming antimesometrial decidual cells with SV-40 tsA 209 mutant virus. These cells express both bFGF and VEGF mRNA. Because progesterone is necessary for decidualization and decidua secretes prolactin (PRL)-related hormones, we examined the role of these hormones on VEGF and bFGF mRNA expressions. Neither progesterone nor PRL had any effect on VEGF mRNA levels. However, bFGF mRNA expression was greatly stimulated by PRL. In conclusion, results of this investigation have revealed that bFGF, but not VEGF, mRNA becomes highly expressed in the mesometrial decidua, where angiogenesis occurs, and where trophoblasts, by invading decidual cells, may promote the release of bFGF. In addition, these results indicate that the locally secreted PRL-like hormone up-regulates the mRNA expression of bFGF.

Animals↗

PubMed1998

Chromosome breaks and sister chromatid exchange as predictors of second cancers in Hodgkin's disease.

Hodgkin's disease (HD) survivors face an increased risk of developing second cancers. We evaluated baseline cytogenetic biomarkers, sister chromatid exchange (SCE) and chromosome breaks [spontaneous (SCB) and bleomycin-induced (BIB)], as predictors of second cancer risk in a cohort of 105 adult HD patients. During follow-up, seven second cancers occurred. SCBs and BIBs showed no association with risk of second primaries. Multivariate Cox regression revealed that high levels of SCEs (relative risk (RR)=11.3, p=0.02) and age (RR=1.08, p=0.02) predicted second cancer risk. Histology, stage, and treatment were not associated with elevated risk. In conclusion, baseline SCE frequencies may be a useful biomarker for identifying HD patients at increased risk of developing second cancers. These results need to be verified in a larger cohort with a longer follow-up time.

Adolescent↗

PubMed1998

The observation of transplanted embryonic motoneurons in the denervated muscles of adult rats.

OBJECTIVE: To observe the survival of embryonic motoneurons after they were transplanted into the denervated skeletal muscles and to find a new method to retard the atrophy of denervated muscles. METHODS: Dissociated embryonic motoneurons prelabled with 5-bromo-2'-deoxyuridine (Brdur) on the embryonic days 12 were injected into the denervated gastrocnemius muscles of adult rats. Then gastrocnemius muscles were processed with Nissl staining, acetylcholinesterase staining and Brdur immunocytochemical staining to show the implanted motoneurons at 9 and 22 weeks post-transplantation. Myofibrillar ATPase staining was used to show the morphology of muscle fibers. The rats in experimental group were implanted with embryonic motoneurons in the predenervation muscles, while the rats in control group were injected with just culture medium without motoneurons. RESULTS: Embryonic motoneurons survived, developed and extended long axons to form neuromuscular junctions with the denervated muscles. The differentiation of muscle fibers and fiber type grouping occurred among bigger fibers in experimental group. The transverse area was smaller and there was no apparent fiber type grouping in control group. CONCLUSIONS: Embryonic motoneurons can survive, develop and reinnervate denervated muscles after being transplanted into denervated muscles. It is worth further investigating on ameliorating the atrophy of denervated muscle.

Animals↗

PubMed1998

Changes of skin perfusion after photodynamic therapy for port wine stain.

OBJECTIVE: To obtain an objective assessment of the curative effectiveness of photodynamic therapy (PDT) for port wine stain (PWS), we investigate the relationship between the microvascular perfusion changes of PWS and the blanching of the lesions before and after PDT. METHODS: Twenty-four patients (18 females and 6 males with a total of 28 lesions) suffering from PWS were treated with PDT. The lesions of various extents were located on the face and neck. After intravenous injection of photosensitizer hepatoporphyrin derivative (HpD), the copper vapor laser was adopted as light source and the lesions of PWS were irradiated. The laser Doppler perfusion imager (LDI) was used to measure the microcirculatory perfusion of PWS before and after PDT and comparison with the normal skin was done. RESULTS: All the lesions showed remarkable decrease of tissue perfusion after PDT. It was shown that the mean, maximal and minimal values of tissue perfusion in the pre-treatment group were significantly higher than those in control group (P < 0.01). Six months after PDT, the mean, maximal and minimal values of perfusion with the lesions were reduced, with significant difference from pre-treatment group (P < 0.01), but no significant difference from control's. The colors of lesions were correlated with decrease of microcirculatory perfusion, which became lightened close to normal skin color without causing any scarring. CONCLUSIONS: PDT is one of the most effective modalities for PWS. The microcirculation perfusion can reflect the degrees of PWS objectively. The curative effectiveness of PDT for PWS is due to tissue microcirculation response.

Adolescent↗

PubMed1998

[Effect of crushing of sciatic nerve on neuron of lumbar spinal cord].

In order to investigate the effect of nerve compression on neurons, the commonly used model of chronic nerve compression was produced in 48 SD rats. The rats were sacrificed in 1, 2, 3, 4, 5 and 6 months after compression, respectively. The number of neuron and ultrashruchure of alpha-motor neurons and ganglion cells of the corresponding spinal segment were examined. The results showed as following: After the sciatic nerve were crushed, the number of neuron and ultrastructure of alpha-motor neurons and ganglion cells might undergo ultrastructural changes, and even the death might occur. These changes might be aggravated as the time of crushing was prolonged and the compression force was increased. It was concluded that for nerve compression, decompression should be done as early as possible in order to avoid or minimize the ultructural changes of the neuron.

Animals↗

PubMed1998

[The effects of clenbuterol on intramuscular collagen metabolism in denervated muscle].

In order to explore the effects of clenbuterol on intramuscular collagen metabolism in denervated skeletal muscles, a randomized, double-masked and placebo-controlled group were studied. Seventy-one patients with complete function loss in muscularcutaneous nerve resulted from brachial plexus injury were administered clenbuterol or placebo 60 micrograms Bid for more than 3 months. Biopsies of the biceps brachia muscle were performed at the beginning and end of this study. The biopsied muscles were processed with anti-collagen I and IV immunohistochemical stains and image analysis as well. The result showed that the collagen proliferation of both type I and IV was much reducible in the clenbuterol-treated group than that of the placebo-treated group (P < 0.05). It was concluded that clenbuterol could inhibit partially the proliferation of intramuscular collagens in denervated skeletal muscle.

Adolescent↗

PubMed1998

[Experimental study of fibrin glue adhesion with epineurial anchor suture to repair peripheral nerves].

To prove and improve the technique of fibrin glue adhesion repair peripheral nerve, 20 male rats were chosen. All the rats was randomly divided into two groups: Suture group (n = 10) and glue adhesion group (n = 10). Left sciatic nerves of the rats were cut with knife and repaired by suture or adhesion methods separately according to their groups. When adhesive method being used, the epineurial was fixed with a suture method similar to anchor suture for preventing suture line broken. Immediatly after the repair and 8 weeks after the surgery, the histologic and electrophysiologic changes of the repaired nerve were observed. The result showed: The axonal copation was soon improved in glue adhesion group. At the eighth week, nerve fiber alignment of the adhesion group was more regular than that of the suture group. Moreover, there were great improvement of axon cross rate and the recovery rate of sectional area of nerve fiber at the distal end in glue adhesion group (P < 0.05, P < 0.01). It was concluded that glue adhesion was prior to suture in repair of peripheral nerve, and anchor suture could improve the technique of glue adhesion method.

Animals↗