Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation.
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Adult↗
Biomedical subjects
S Yu
Publications and source records attributed to S Yu.
The lowering effect of high copper intake on selenium retention in weanling rats depends on the selenium concentration of the diet.
The question addressed was whether the influence of dietary copper concentration on selenium metabolism depends on the amount of selenium in the diet. Weanling, male rats were fed purified diets containing either 1 (low), 4 (normal) or 42 (high) mg Cu/kg diet and either 0.03 (low), 0.05 (normal) or 1.0 (high) mg Se/kg diet in a 3(2) factorial design. Extra copper was added to the diets in the form of CuSO(4) x 5H(2)O and selenium as Na(2)SeO(3) x 5H(2)O. In rats fed either the low or normal amounts of selenium, higher intakes of copper decreased the apparent intestinal selenium absorption and increased urinary selenium excretion. The effects of copper on selenium absorption, excretion and retention were not seen in rats fed the high-selenium diets. An increase in dietary copper concentrations elevated selenium concentrations in the liver and kidneys, but slightly lowered those in the spleen of rats that were fed the diets with the normal level of selenium. In rats that were fed the diets with either low or high selenium concentration, copper intake had no effect on organ selenium concentrations. Glutathione peroxidase activity in erythrocytes was raised by feeding the diets which contained either normal or high copper content instead of those that were low in copper. It is concluded that the amount of selenium in the diet determines whether or not an increase in dietary copper concentration affects selenium metabolism.
Animals↗
Dietary lactulose decreases apparent nitrogen absorption and increases apparent calcium and magnesium absorption in healthy dogs.
To study the effect of lactulose on the route of nitrogen excretion, we fed six healthy, adult dogs on diets containing either 0, 1 or 3 g lactulose/MJ metabolizable energy according to a 3 x 3 Latin square design. The results were analysed to identify statistically significant linear trend effects of lactulose. Faecal pH was significantly lowered by lactulose. Faecal ammonium and nitrogen excretion tended to be raised by lactulose feeding whereas urinary urea excretion was significantly reduced. Lactulose feeding significantly lowered apparent nitrogen digestibility. It is concluded that lactulose feeding shifts nitrogen excretion from urine to faeces in dogs which may be beneficial for liver patients. The data are in line with the concept that lactulose stimulates bacterial growth in the colon which in turn enhances faecal nitrogen excretion and lowers the entry of colonic ammonia into the bloodstream, leading to a lesser workload for the liver and less urinary nitrogen excretion. Lactulose consumption was also found to produce a dose-dependent increase in the apparent absorption of calcium and magnesium, but not phosphorus.
Animals↗
Special aspects of cancer pain management in a Chinese general hospital.
China is still faced with a challenge in cancer pain management. The purposes of this study are to assess the current status of cancer pain management, and physicians' attitudes in China towards cancer pain management. The survey was done in a Chinese general hospital; 427 physicians and 387 cancer pain patients participated. The survey consisted of questionnaires to evaluate cancer pain management and physicians' knowledge of, and attitudes towards, cancer pain management. A total of 43% of patients with cancer pain and 51% with bone pain felt that they had been inadequately treated. The physicians rated the main reason for not using opioid drugs as the strong and difficult to control side-effects. The four main barriers to optimal management of cancer pain were: inadequate pain assessment; excessive state regulation of the prescribing of opioids; inadequate staff knowledge of pain management; and lack of access to powerful analgesics. To conclude: In China, there are some special aspects of cancer pain management, including physicians' concern about using opioid drugs, fear of being unable to manage adverse effects of opioids, and inadequately treated bone pain.
Adolescent↗
Portal venous ultraviolet B-irradiated donor alloantigen prevents rejection in circumferential rat tracheal allografts.
BACKGROUND: Before tracheal transplantation can be considered as a method of reconstruction in patients with extensive circumferential tracheal defects, we must achieve a state of nontoxic, donor-specific tolerance so that the risks of such a transplant do not outweigh the benefits. OBJECTIVE: Our objective was to determine whether a single intraportal injection of modified donor alloantigen achieves donor-specific immunosuppression for major histocompatibility complex-mismatched rat tracheal allografts. STUDY DESIGN: Buffalo (recipient) rats were pretreated with either a single portal-vein administration of ultraviolet B (UVB)-irradiated donor splenocytes (n = 4) or an intraportal inoculation of nonirradiated donor splenocytes (n = 4). Major histocompatibility complex-mismatched Lewis (donor) tracheal allograft segments were then grafted into treatment groups 7 days after donor-cell pretreatment. Tracheal rejection was assessed by histologic analysis, mucosal cilia motility, and in vitro immunologic assessment. RESULTS: The UVB-treated group demonstrated no acute or chronic rejection as well as complete functional recovery. In vitro immunologic assessment demonstrated a donor-specific hyporesponsiveness and donor allospecificity. Untreated animals and those receiving nonirradiated donor splenocytes showed acute rejection of their tracheal allografts. CONCLUSION: Recipient pretreatment with intraportally administered UVB-irradiated donor splenocytes prevents rejection of circumferential rat tracheal allograft segments by inducing a donor-specific immune hyporesponsiveness.
Animals↗
Immunogenicity of L(d+) transgenic mouse hearts.
BACKGROUND: C57BL/6 mice transfected with the L(d) gene coupled to the alpha-myosin heavy chain promoter result in transgenic mice with L(d) antigen expressed only on cardiac tissue. These transgenic animals allow the examination of immune reactivity against cardiac L(d) by "self" or by adoptively transferred L(d) specific 2C cells, and the response of nontransgenic C57BL/6 mice to the transplanted L(d+) heart. METHODS: Naïve cardiac L(d+) transgenic mice were examined for evidence of L(d) "autoimmunity." Forty million fresh 2C cells or 2C cells sensitized in vitro for 7 days against Balb/c (L(d+)) + interleukin-2 were also given intravenously to L(d+) transgenic mice. At 5 and 12 days after injection, heart-infiltrating lymphocytes were analyzed by fluorescence-activated cell sorter. The L(d+) transgenic hearts were also transplanted to syngeneic L(d-) nontransgenic C57BL/6 to evaluate the heart's immunogenicity. RESULTS: Naïve L(d+) transgenic mice did not exhibit any evidence of lymphocytic infiltration on histologic examination. Adoptive transfer of either fresh or in vitro sensitized 2C cells was also unable to reject the native L(d+) heart in transgenic mice (100% of the mice survived long term [more than 60 days]). Sensitization of the L(d+) transgenic mice with a Balb/c skin graft and interleukin-2 pump infusion (7 days) beginning 1 day before 2C cell injection also did not promote rejection of the native L(d+) heart. However, fluorescence-activated cell sorter analysis did reveal that a significantly greater number of in vitro sensitized 2C cells homed to the L(d+), but not L(d-), heart after both 5 and 12 days (P <.01, P <.001). In contrast, C57BL/6 mice rejected the L(d+) (C57BL/6 background) transgenic heart in a mean survival time of 17 +/- 9.7 days (P <.01), whereas a syngeneic C57BL/6 heart transplant was accepted indefinitely. Lymphocytic infiltration consistent with rejection was present in all animals receiving an Ld+ transgenic heart transplant, whereas no infiltrate was present in those receiving a syngeneic C57BL/6 heart transplant. CONCLUSIONS: Although the class I L(d) transgene is not recognized in its native host, its immunogenicity is shown by the homing of anti-L(d) 2C cells to the heart in situ and rejection of L(d+) heart grafts when transplanted into syngeneic C57BL/6 mice.
Adoptive Transfer↗
Preparation of a ribonucleic acid-(polyamidoamine)-(zirconia-urea-formaldehyde resin) high-performance liquid affinity chromatographic stationary phase.
A preparative method for a high-performance liquid affinity chromatographic (HPLAC) stationary phase is described. The 3- to 5-microm nonporous composite spherical microparticles of zirconia and urea-formaldehyde (UF) resin are synthesized through the reaction of zirconyl chloride with hexamethylene tetra-amine and urea, and then it is used as the matrix of the HPLAC stationary phase of which the diameter and structure are determined by scanning electron microscopy. In a methanol medium, the polyamidoamine (PAMAM) starburst dentritic spacer arms are linked with the imido-groups on the surface of the matrix by the Michael addition reaction with methyl acrylate and the amination reaction with ethylene diamine. After repeating these steps in triplets, amine-terminated dentritic spacer arms with a generation of 3 are obtained. The topological structure of the spacer arms is examined by solid-state 13C NMR. The Br-substituted ribonucleic acid (RNA) ligand is obtained by the reaction of liquid bromine with RNA and bonded to the dendritic spacer arms of the matrix in a solution of NaOH (pH 9-11). The binding capacity of RNA is measured by UV spectrophotometry. A new type of stationary phase--RNA-(PAMAM)-(zirconia-UF resin--for HPLAC, which possesses starburst dendritic spacer arms, is synthesized and used for the separation of biological macromolecules.
Adenine Nucleotides↗
Pretreatment with portal venous ultraviolet B-irradiated donor alloantigen promotes donor-specific tolerance to rat nerve allografts.
OBJECTIVE: To determine if a single intraportal inoculation of ultraviolet B-irradiated (UVB) donor splenocytes can prevent nerve allograft rejection and confer donor-specific immunotolerance to rat nerve allograft segments. METHODS: Age-matched, class I and class II major histocompatibility complex (MHC) mismatched Buffalo (RT1b) rats were transplanted with a syngeneic nerve isograft, a Lewis (RT1l) nerve allograft, or a Brown-Norway (RT1n) rat nerve allograft segment. Control Buffalo rats in group I received a 3.0-cm Lewis (RT11) sciatic-posterior tibial interposition nerve allograft without pretreatment; group II Buffalo rats received a syngeneic Buffalo nerve isograft without pretreatment. Group III Buffalo recipients were inoculated with 2.5 x 107 UVB-irradiated Lewis donor splenocyte cells by portal venous administration 7 days before transplantation with a 3.0-cm sciatic-posterior tibial nerve allograft from a Lewis (RT11) or a third party Brown-Norway rat (RT1n) donor (group IV). Nerve graft regeneration was assessed with walking track analysis, nerve conduction studies, retrograde neural tracing, nerve graft histology, and morphometry. Recipient immune tolerance was assessed through in vitro immunological assessment. RESULTS: Pretreatment with UVB-irradiated donor splenocytes 7 days before transplantation prevented nerve allograft rejection. Pretreated animals receiving a nerve allograft recovered limb function, and demonstrated morphological, histological, and electrophysiologic parameters of nerve regeneration similar to that measured in rats receiving a nerve isograft. In vitro immunological assessment by mixed lymphocyte culture (MLC), cytotoxic T lymphocyte (CTL) assay, limiting dilution analysis (LDA) of helper (pTH) and cytotoxic (pCTL) precursor frequencies, and IL-2 production demonstrated a marked donor-specific suppression in allografted animals pretreated with intraportal UVB-irradiated donor splenocytes. These assessments correlated with indefinite acceptance of donor nerve allografts. CONCLUSIONS: A single pretreatment with a single intraportal dose of UVB-modified donor antigen specifically induces tolerance to peripheral nerve allografts in rats.
Animals↗
Sugar coordinately and differentially regulates growth- and stress-related gene expression via a complex signal transduction network and multiple control mechanisms.
In plants, sugars are required to sustain growth and regulate gene expression. A large set of genes are either up- or down-regulated by sugars; however, whether there is a common mechanism and signal transduction pathway for differential and coordinated sugar regulation remain unclear. In the present study, the rice (Oryza sativa cv Tainan 5) cell culture was used as a model system to address this question. Sucrose and glucose both played dual functions in gene regulation as exemplified by the up-regulation of growth-related genes and down-regulation of stress-related genes. Sugar coordinately but differentially activated or repressed gene expression, and nuclear run-on transcription and mRNA half-life analyses revealed regulation of both the transcription rate and mRNA stability. Although coordinately regulated by sugars, these growth- and stress-related genes were up-regulated or down-regulated through hexokinase-dependent and/or hexokinase-independent pathways. We also found that the sugar signal transduction pathway may overlap the glycolytic pathway for gene repression. alpha-Amylase and the stress-related genes identified in this study were coordinately expressed under sugar starvation, suggesting a convergence of the nutritional and environmental stress signal transduction pathways. Together, our studies provide a new insight into the complex signal transduction network and mechanisms of sugar regulation of growth and stress-related genes in plants.
DNA, Complementary↗
Effect of low levels of dietary tyrosine on the hair colour of cats.
Experiments were conducted to investigate the basis for the change in hair colour of black cats to reddish-brown. Black cats were given purified diets based on gelatin, casein plus lactalbumin, or crystalline amino acids as protein sources. Diets that caused the colour of hair to change to reddish-brown were associated with a reduction in melanin in hair (observed by direct microscopic examination), a decreased total melanin concentration and low concentrations of tyrosine in plasma. Reddish hair coat was induced in black kittens born to queens given a tyrosine-deficient diet during pregnancy. Black hair colour was maintained or restored by diets containing a high concentration of tyrosine or phenylalanine. Current dietary recommendations for dietary tyrosine and phenylalanine for cats are below those required to support maximal melanin synthesis in black cats. The requirement appears to be greater than a combination of 4.5 g tyrosine plus 12 g phenylalanine/kg diet but less than 24 g phenylalanine alone/kg diet.
Amino Acids↗
Effects of jiawey siwu on rat activity.
Jiawey siwu (JS) is a modified formula of siwu with the addition of Ginseng Radix and Eucommiae Cortex. We studied the CNS effect of JS on pentobarbital-induced hypnosis in ICR mice after acute oral administration. We also investigated the motor activity and exercise performance effects of JS in SD rats after subchronic (12 days) and chronic (8 weeks) oral administration with an activity cage and rotarod, respectively. The duration of pentobarbital-induced hypnosis was significantly decreased in mice after acute oral administration of 0.21, 1.05 or 4.2 g/kg JS. The time of ambulatory activity and time on the rotarod significantly increased in rats after subchronic and chronic oral administration of 1.05 g/kg JS, respectively. These results indicate that JS potentially increased the excitability of the CNS in mice, as well as increasing motor activity and physical endurance in rats.
Animals↗
Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting.
The heterotrimeric G protein G(s) couples hormone receptors (as well as other receptors) to the effector enzyme adenylyl cyclase and is therefore required for hormone-stimulated intracellular cAMP generation. Receptors activate G(s) by promoting exchange of GTP for GDP on the G(s) alpha-subunit (G(s)alpha) while an intrinsic GTPase activity of G(s)alpha that hydrolyzes bound GTP to GDP leads to deactivation. Mutations of specific G(s)alpha residues (Arg(201) or Gln(227)) that are critical for the GTPase reaction lead to constitutive activation of G(s)-coupled signaling pathways, and such somatic mutations are found in endocrine tumors, fibrous dysplasia of bone, and the McCune-Albright syndrome. Conversely, heterozygous loss-of-function mutations may lead to Albright hereditary osteodystrophy (AHO), a disease characterized by short stature, obesity, brachydactyly, sc ossifications, and mental deficits. Similar mutations are also associated with progressive osseous heteroplasia. Interestingly, paternal transmission of GNAS1 mutations leads to the AHO phenotype alone (pseudopseudohypoparathyroidism), while maternal transmission leads to AHO plus resistance to several hormones (e.g., PTH, TSH) that activate G(s) in their target tissues (pseudohypoparathyroidism type IA). Studies in G(s)alpha knockout mice demonstrate that G(s)alpha is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in some tissues (e.g., renal proximal tubule, the major site of renal PTH action), while being biallelically expressed in most other tissues. Disrupting mutations in the maternal allele lead to loss of G(s)alpha expression in proximal tubules and therefore loss of PTH action in the kidney, while mutations in the paternal allele have little effect on G(s)alpha expression or PTH action. G(s)alpha has recently been shown to be also imprinted in human pituitary glands. The G(s)alpha gene GNAS1 (as well as its murine ortholog Gnas) has at least four alternative promoters and first exons, leading to the production of alternative gene products including G(s)alpha, XLalphas (a novel G(s)alpha isoform that is expressed only from the paternal allele), and NESP55 (a chromogranin-like protein that is expressed only from the maternal allele). A fourth alternative promoter and first exon (exon 1A) located approximately 2.5 kb upstream of the G(s)alpha promoter is normally methylated on the maternal allele and transcriptionally active on the paternal allele. In patients with isolated renal resistance to PTH (pseudohypoparathyroidism type IB), the exon 1A promoter region has a paternal-specific imprinting pattern on both alleles (unmethylated, transcriptionally active), suggesting that this region is critical for the tissue-specific imprinting of G(s)alpha. The GNAS1 imprinting defect in pseudohypoparathyroidism type IB is predicted to decrease G(s)alpha expression in renal proximal tubules. Studies in G(s)alpha knockout mice also demonstrate that this gene is critical in the regulation of lipid and glucose metabolism.
Animals↗
Thyroid stimulating hormone secretion is a dynamic process.
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Aged↗
High arsenic intake raises kidney copper and lowers plasma copper concentrations in rats.
The effect of high arsenic intake on copper metabolism was investigated. Male rats aged 6 wk had free access to purified diets containing either 0 or 100 mg As/kg diet and demineralized water for a period of 2 wk. Arsenic was added to the diet in the form of NaAsO2. The high-arsenic diet decreased feed and water intake and body weight gain, but significantly increased liver weight. Kidney weight was not affected. Arsenic feeding drastically elevated kidney copper concentration, but significantly reduced copper concentration in plasma. Both true absorption and biliary excretion of copper were decreased significantly in rats fed the high-arsenic diet. True copper absorption was lowered essentially through the lower copper intake in the rats fed arsenic. It is speculated that arsenic feeding primarily leads to copper accumulation in the kidney, followed by a decrease in feed intake and thus in true, absolute copper absorption, a decrease in plasma copper concentration, and a decrease in biliary copper excretion.
Animals↗
Protein kinase CK2 signal in neoplasia.
Protein kinase CK2 (previously known as casein kinase II) is a protein serine/threonine kinase that has been implicated in cell growth and proliferation. The focus of this review is on the apparent role of CK2 in cancer. Studies from several laboratories have shown a dysregulated expression of the kinase in tumors. Nuclear matrix and chromatin appear to be key sites for signaling of the CK2 activity in relation to cell growth. Several types of growth stimuli produce a common downstream response in CK2 by enhancing its nuclear shuttling. The neoplastic change is also associated with changes in intracellular localization of the kinase so that a higher nuclear localization is observed in tumor cells compared with normal cells. Experimental studies suggest that dysregulated expression of the alpha subunit of CK2 imparts an oncogenic potential in the cells such that in cooperation with certain oncogenes it produces a profound enhancement of the tumor phenotype. Recent studies have provided evidence that overexpression of CK2 in tumor cells is not simply a reflection of tumor cell proliferation alone but additionally may reflect the pathobiological characteristics of the tumor. Of considerable interest is the possibility that CK2 dysregulation in tumors may influence the apoptotic activity in those cells. Approaches to interfering with the CK2 signal may provide a useful means for inducing tumor cell death.
Adenocarcinoma↗
Measurement of tumor blood flow using colored dye extraction microspheres in two rat tumor models.
A technique that can measure tumor blood flow easily, accurately and economically is required to study tumor angiogenesis and angiogenesis inhibition. Using dye extraction colored microspheres, we measured tumor blood flow in Sato lung carcinoma (SLC) and ascites hepatoma LY80 in rats. Colored microspheres were infused into tumor-bearing rats via a catheter in the left ventricle. After removal of the tumor and the liver, the tissue samples were dissolved, and the microspheres were isolated. Dye was extracted, and the dye concentration was quantified by spectrophotometry. The dye concentration per gram of tumor was compared with that per gram of liver as follows (AU = absorbency units): [AU per gram of tumor] / [AU per gram of liver] X 100 = (%). Tumor blood flow corrected for wet weight was calculated as follows: [blood flow to tumor] = [AU per gram of tumor] X [reference withdrawal rate] / [AU per gram of reference blood]. Tumor blood flow rate was divided by tumor weight to yield ml. min-1g-1. The tumors were also examined histologically, and casts of the tumor vasculature were prepared with silicone rubber. Blood flow 2 weeks after transplantation was equivalent to 1/10 and 1/2 at 1 week in SLC and LY80 tumors, respectively (SLC, P=0.009, n=10; LY80, P=0.05, n=10). These decreases in tumor blood flow were associated with underlying pathological and vascular change. Blood flow in LY80 tumors negatively correlated with tumor volume (P=0.009, n=10). We concluded that the colored microsphere method, initially developed to measure organ blood flow, is also useful for estimating tumor blood flow in rats.
Animals↗
Regulation of hepatic cytochrome P450 2C11 via cAMP: implications for down-regulation in diabetes, fasting, and inflammation.
The effect of glucagon and its second messenger cAMP on cytochrome P450 2C11 (CYP2C11) expression was investigated in primary hepatocytes cultured on Matrigel. Glucagon, epinephrine, forskolin, and the cAMP derivatives dibutyryl cAMP, (S(p))-adenosine 3',5' cyclic monophosphothioate (S(p)-cAMPS), and 8-(4-chlorophenylthio)-cAMP, but not dideoxyforskolin, all down-regulated CYP2C11 mRNA expression to approximately 20% of control levels in a concentration-dependent manner. Using the transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, CYP2C11 mRNA was found to have a half-life of 9.8 h. The kinetics of suppression of CYP2C11 mRNA by glucagon and forskolin was similar to that obtained with the transcriptional inhibitor, suggesting that glucagon and forskolin act at the transcriptional level. CYP2C11 expression was more sensitive to suppression by glucagon at low insulin concentrations than at higher concentrations. (R(p))-Adenosine 3',5' cyclic monophosphothioate inhibited the down-regulation of CYP2C11 by S(p)-cAMPS, consistent with a competitive blockade of protein kinase A activation. These results suggest a role for glucagon in the down-regulation of CYP2C11 in diabetic rats, and provide a possible explanation for the known sensitivity of this cytochrome P450 to suppression in various stress and disease models.
Animals↗
Infant mortality in Louisiana--identifying the risks.
The state of Louisiana consistently has one of the five highest infant mortality rates in the nation and the racial disparity within the state is glaring. The purpose of this paper is to analyze the state's linked birth and death infant data set for the birth cohort of 1990-1998, and to identify the "at risk" population. We have analyzed data from the 1990 to 1998 birth and infant death cohort in Louisiana to determine mothers' characteristics that are associated with infant death. These include extremely young and old ages, unmarried marital status, lower levels of education, and prenatal care. A mother's race is also associated with higher future mortality for her infant, with black mothers and their infants being at greater risk than white ones. Because the infant mortality rate is higher for black infants than for white ones, Louisiana's higher infant mortality rate can be seen as a result of the higher proportion of black births. Main concerns in reducing infant mortality rates include reducing incidence of low birth weights specifically among black births primarily by providing adequate prenatal care.
Adolescent↗