Search PubMed⌕ Search

Biomedical subjects

B Han

Publications and source records attributed to B Han.

At least 127 records · Page 7Linked to original sources
PubMed1996

[Effects of high salt-loading on the regulation of angiotensin II receptor mRNA expression].

In the present study, the angiotensin II receptor subtype I-a (AT1a) and I-b (AT1b) mRNA levels in aortic smooth muscle (ASM), ventricular myocardium (VM) and adrenal from 12-week-old stroke-prone spontaneously hypertensive rats (SHRsp) and age-matched Wistar-Kyoto (WKY) rats with normal diet (control) and high salt-loading were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that: (1) The AT1a and AT1b mRNA levels in ASM and VM from SHRsp were lower than those from WKY rats (in ASM, 10% and 23%, while in VM, 23% and 40% lower, respectively). In contrast, both AT1a and AT1b mRNA levels in adrenal from SHRsp were higher (176% and 157%, respectively). (2) In the WKY rats with high salt-loading, the AT1a and AT1b mRNA levels in adrenal, as well as AT1b mRNA level in VM, increased significantly, as compared with the control (in adrenal, 167% and 401%, while in VM, 62%). However, the AT1a and AT1b mRNA levels in ASM, as well as AT1a mRNA level in VM, showed no obvious change. (3) In SHRsp with high salt-loading, the AT1b mRNA level in ASM, as well as AT1a and AT1b mRNA levels in VM, increased markedly (in ASM, 90%, while in VM, 590% and 200%); whereas the AT1a mRNA level in adrenal decreased significantly (58%). There was little influence on the regulation of AT1a (in ASM) and AT1b (in adrenal) receptor gene expression after high salt-loading. The results suggest that AT1a and AT1b receptors may be involved in the pathogenesis of salt-induced hypertension. The up-regulation of AT1b receptors in ASM may induce the remodeling of arterial wall, while that of AT1a and AT1b receptors in VM might contribute to ventricular hypertrophy in hypertension. Furthermore, there are certain differences between SHRsp and WKY rats with respect to the regulation of AT1a and AT1b receptor gene expression with or without external stimulation.

Adrenal Glands↗
PubMed1996

[Changes of Kupffer cell DNA and RNA synthetic functions after partial hepatectomy in cirrhotic rats].

We studied the changes of DNA and RNA synthetic functions of regenerating liver cells after partial hepatectomy in cirrhotic rats and discussed the relationship between liver regeneration and liver functional failure. Seventy healthy male Wistar rats weighing 200 approximately 250 g, were randomized into sham-operated (SO), partial hepatectomy in cirrhotic rats (C-PH) and partial hepatectomy in normal rats (N-PH). The left and middle lobes were dissected. The synthetic DNA peak of Kupffer cells (KC) in the G2 and M phase in C-PH was found after 24 hr of operation. The regenerating index peak of KC was at 48 hr after operation, which was higher than the other groups, but the liver weights in C-PH was lower than that in the N-PH at 1 week after operation. The RNA content of KC markedly decreased and returned to normal levels at 1 week after operation. We think that KC functions are suppressed after partial hepatectomy in cirrhotic rats. It is an important cause of hepatocyte regeneration function decrease and liver functional failure for delay of liver cell regeneration "start" and the regeneration cell cycle.

Animals↗
PubMed1996

[Pathological study on the metastatic routes of bile duct carcinoma].

Multiple staining was performed on resected tumors. Samples after curative surgery in 40 cases of bile duct carcinoma for observation of tumor blood vessel density (TVD), and perineural invasion index (PNI). Lymphatic invasion was found in 29 cases (72.5%), blood vessel invasion in 31 (77.5%), and PNI in 33 (82.5%). TVD and PNI were positively correlated with metastasis. Three years after operation, the recurrent rate was 100%, with an averaging recurrent time of 9.6 months in the metastatic group in contrast to 64.3% and 17.5 months in those without metastasis.

Adenocarcinoma↗
PubMed1995

Identification of Asn289 as a ligand binding site in the rat thyrotropin-releasing hormone (THR) receptor as determined by complementary modifications in the ligand and receptor: a new model for THR binding.

To test the hypothesis that pGlu of the thyrotropin-releasing hormone (TRH, pGlu-His-ProNH2) binds to Asn289 in the third extracellular loop (EL3) of its receptor through a hydrogen bonding interaction, we converted Asn289 to Asp (N289D mutant) and measured the potencies of TRH and Pro1TRH for the wild-type and mutant receptors. TRH was 100 times less potent for the N289D receptor than for the wild-type. In contrast, Pro1TRH, which has a protonated proline in place of the pGlu of TRH, was 10 times more potent for the N289D receptor than for the wild-type. A similar result was obtained when Asn289 was converted to Glu, while the potency of Pro1TRH did not change when Asn289 was converted to Ala, confirming that the increased potency of Pro1TRH for the N289D receptor was due to a charge interaction between Pro1TRH and the mutant receptor. These findings are inconsistent with a previous model indicating a direct interaction of the pGlu of TRH with Asn110 in the third transmembrane helix of the receptor (Perlman et al. (1994) J. Biol. Chem. 269, 23383-23386). When Asn110 was converted to Asp (N110D mutant), unlike the N289D receptor, the potency of Pro1TRH for the N110D receptor was decreased by > 10-fold rather than increased. Therefore, a direct interaction of Asn110 with the pGlu of TRH could not be supported by our experiments. We propose a new model in which the pGlu of TRH binds to Asn289 in EL3 and conclude that, unlike catecholamines which bind completely within the transmembrane domain of their receptors, this tripeptide binds, at least in part, to the extracellular domain of its receptor.

Amino Acid Sequence↗
PubMed1995

Behavioral performance of Swiss Webster mice exposed to excess dietary aluminum during development or during development and as adults.

Swiss Webster mice were exposed to excess dietary aluminum (500 or 1000 micrograms Al/g as Al lactate) from conception until weaning or from conception through adulthood (pre- and postweaning). Controls were fed a 7 micrograms Al/g diet. Excess Al diets did not influence pregnancy outcome, pup mortality, and body or organ weights. Al diets of 1000 micrograms/g led to enhanced cagemate aggression in offspring as adults. At 50 days of age, mice were trained for operant tasks and subsequently 35 sessions of delayed spatial alternation or discrimination reversal testing were conducted. Both the 500 and the 1000 micrograms Al/g diets led to faster attainment of criterion during the training phase of the operant studies, but did not influence performance of the two tasks. At the conclusion of the study (150-170 days of age), neurobehavioral measures and tissue trace metals (Al, Fe, Mn) were determined. Both the 500 and the 1000 micrograms Al/g diets led to reduced grip strength and the 1000 micrograms Al/g diet was associated with lower Fe concentrations in brain and spinal cord. Brain, spinal cord, and liver Al concentrations were elevated only in adults with continued exposure after weaning. Throughout the experiment, mice exposed before and after weaning were apparently no more affected on behavioral measures than those exposed only until weaning. It is concluded that developmental exposure to 500 and the 1000 micrograms Al/g diets had distinctive long-term effects on behavioral measures that were not dose dependent and were not further intensified by continuing exposure as adults.

Aggression↗
PubMed1995

Identification and characterization of a locus which regulates multiple functions in Pseudomonas tolaasii, the cause of brown blotch disease of Agaricus bisporus.

Pseudomonas tolaasii, the causal agent of brown blotch disease of Agaricus bisporus, spontaneously gives rise to morphologically distinct stable sectors, referred to as the phenotypic variant form, at the margins of the wild-type colonies. The phenotypic variant form is nonpathogenic and differs from the wild type in a range of biochemical and physiological characteristics. A genomic cosmid clone (pSISG29) from a wild-type P. tolaasii library was shown to be capable of restoring a range of characteristics of the phenotypic variant to those of the wild-type form, when present in trans. Subcloning and saturation mutagenesis analysis with Tn5lacZ localized a 3.0-kb region from pSISG29, designated the pheN locus, required for complementation of the phenotypic variant to the wild-type form. Marker exchange of the Tn5lacZ-mutagenized copy of the pheN locus into the wild-type strain demonstrated that a functional copy of the pheN gene is required to maintain the wild-type pathogenic phenotype and that loss of the pheN gene or its function results in conversion of the wild-type form to the phenotypic variant form. The pheN locus contained a 2,727-bp open reading frame encoding an 83-kDa protein. The predicted amino acid sequence of the PheN protein showed homology to the sensor and regulator domains of the conserved family of two component bacterial sensor regulator proteins. Southern hybridization analysis of pheN genes from the wild type and the phenotypic variant form revealed that DNA rearrangement occurs within the pheN locus during phenotypic variation. Analysis of pheN expression with a pheN::lacZ fusion demonstrated that expression is regulated by environmental factors. These results are related to a model for control for phenotypic variation in P. tolaasii.

Agaricus↗
PubMed1995

Importance of extracellular domains for ligand binding in the thyrotropin-releasing hormone receptor.

The role of putative extracellular sequences for ligand binding in the TRH receptor was examined using deletion or substitution mutations. Each mutant receptor was transiently expressed in TRH receptor-minus GH(1)2C(1)b rat pituitary cells, and binding of 4 Nu Mu [3H]pGlu-N(tau)-MeHis-Pro-NH2 ([3H] MeTRH) was measured. When binding was not detected, signal transduction at 10 microM MeTRH was measured to assess receptor expression. Deletion of most of the N-terminal sequences (Glu(2)-Leu(22)), including two potential glycosylation sites, had no effect on the affinity of the receptor for MeTRH. Segmental deletions or simultaneous substitution of multiple amino acid residues in the first, second, or third extracellular loop (EL1, EL2, or EL3) resulted, however, in total loss of [3H]MeTRH binding, suggesting important roles for the loop sequences in either receptor expression or ligand binding. Individual substitutions were made to test further the role of the specific extracellular loop sequences in TRH binding. In EL1, conversion of Tyr93 to Ala resulted in more than 20-fold decrease in affinity for MeTRH. In EL2 and the top portion of the fifth transmembrane helix, conversion of Tyr181 to Phe, Tyr188 to Ala, and Phe199 to Ala resulted in a large ( > 100-fold) decrease in affinity for MeTRH, and conversion of Tyr 188 to Phe and Phe196 to Ala caused an agonist-specific 4- to 5-fold decrease in affinity. In EL3, conversion of Asn289 to Ala and of Ser290 to Ala caused a large ( > 100-fold) decrease in affinity for MeTRH. These results suggest important roles for the extracellular loops in high affinity TRH binding and lead us to propose a model in which TRH binds to the extra-cellular domain of its receptor.

Amino Acid Sequence↗
PubMed1995

Agonist-independent, muscle-type-specific signal transduction pathways in cat esophageal and lower esophageal sphincter circular smooth muscle.

Smooth muscle cells isolated from the circular muscle layer of cat esophagus and lower esophageal sphincter (LES) exhibit distinct contractile intracellular signal transduction pathways in response to acetylcholine. To determine whether these contractile pathways are muscle type dependent, the authors examined the signal transduction pathways utilized by substance P and bombesin, which in other tissues, use different signal transduction pathways, and by the GTP analog, guanosine 5'-O-3-thiotriphosphate (GTP gamma S), which activates all available G proteins. Western blot analysis of esophageal and LES circular muscle revealed the presence of Gq-G11 (42 kD), Gi1-Gi2 (40 kD) and Go-Gi3 (40 kD) types of G proteins. The responses of esophageal cells to bombesin and substance P were blocked by 1) a Gi3 protein antibody, 2) the inhibitor of specific phosphatidylcholine-phospholipase C (PLC) D609 potassium tricyclo-[5.2.1.0(2.6)]-decyl-(9[8])-xanthogenate, 3) inhibition of phosphatidic acid phosphohydrolase by propranolol, 4) the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and 5) incubation in Ca(++)-free medium. Conversely, the responses of LES muscle cells to bombesin and substance P were blocked by 1) a Gq-G11 antibody, 2) a phosphatidylinositol-specific PLC antagonist U-73122 (1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17- yl]amino]hexyl]-1H-pyrrole-2,5-dione), 3) the calmodulin inhibitor CGS9343B (1,3-Dihydro-1-[1-((4-methyl-4H,6H-pyrrolo[1,2-a]-[4,1]benzoxazepin++ +-4 - yl)methyl-4-piperindinyl]-2H-benzimidazol-2-one maleate) and 4) incubation in Sr++. After permeabilization by saponin, inositol 1,4,5-trisphosphate contracted LES but not esophageal cells. The inositol 1,4,5-trisphosphate receptor antagonist heparin and depletion of intracellular Ca++ stores by thapsigargin or A23187 4-Benzoxazolecarboxylic acid, 5-(methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol- 2-yl)ethyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-, [6s-[6.alpha. (2S*,3S*),8.beta. (R*), 9.beta., 11. alpha.]]-(9Cl), blocked bombesin- and substance P-induced contraction of LES but not of esophageal muscle. In addition, contraction in response to GTP gamma S, which activates all G proteins, was blocked in esophageal cells by a Gi3-protein antibody, propranolol, D609 and H7. In LES muscle cells, the response to GTP gamma S was blocked by a Gq protein antibody, U-73122 and CGS934B. These data demonstrate that, in esophageal muscle, different agonists activate the same Gi3 protein, phosphatidylcholine-specific phospholipases and protein kinase C-dependent pathway.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

[Adoptive immunotherapy of malignant pleural effusion with TIL/rIL2 (tumor-infiltrating lymphocytes/recombinant interleukin 2)].

TIL of 24 patients with malignant pleural effusions were induced and expanded in vitro. The phenotype of lymphocytes IL2R, NK cytotoxicity activity were analysed in fresh and activated TIL. CEA and cytology of malignant pleural effusion were detected before and after treatment with TIL/rIL2. The results indicated: CD4.CD8.IL2R, NK activity increased markedly, CEA level decreased in all of the patients, tumor cells disappeared in some patients. The pleural effusion disappeared in 63%. The total effective rate of the treatment is 79%. No serious toxicity and side effects were found in 1 to 6 months period of following-up after treatment.

Adult↗
PubMed1995

[Role of type IV collagenase in tumor cell invasion and effect of laminin on invasive potential in bile duct carcinoma].

In the present experiment, the secretion of type IV collagenase, the invasive potential of tumor cell in vitro, and the effects of exogenous laminiu and anti-laminin antibody on the invasive potential of tumor cells in a newly established cell line of bile duct carcinoma, QBC939, were observed by using an amnion invasion culture system and a substrate capture immunoassay. The biological mechanism of tumor invasion, especially the role of the type IV collagenase in the invasive process, was discussed. QBC939 cells secreted type IV collagenase with high invasive potential. Different doses of laminin (1 micrograms, 5 microgram, 10 microgram/ml) stimulated the release of type IV collagenase and increased the invasive potential of the tumor cells in varying degrees. The effect of laminin could be antagonized by the anti-laminin antibody. The results demonstrate that the type IV collagenase is one of the important enzymes involved in the tumor invasion. The effects of laminin on the release of type IV collagenase and the invasive potential suggest that laminin play an important role in mediation of tumor invasion. The results also suggest that inhibiting type IV collagenase or blocking the effect of laminin on tumor cells may be a prospective therapy for tumor treatment in future.

Antibodies↗
PubMed1995

A canine model for determination of the therapeutic index of cytokine inhibitors.

Using tumor necrosis factor (TNF) inhibition in dog blood as a measure of efficacy, and canine emesis as a measure of toxicity, we were able to assign a therapeutic index to rolipram, a prototypic anti-inflammatory compound. Because both assays were performed in the same species, the ambiguities associated with comparing the physiologic effects of drugs on various species was avoided. Rolipram, a standard phosphodiesterase type IV inhibitor, was a prototypic test compound characterized by a number of cardiovascular and central nervous system side effects, as well as its in vitro and in vivo inhibition of TNF. Initial experiments with canine whole blood incubated with lipopolysaccharide resulted in nanogram-per-milliliter concentrations of TNF that could be significantly reduced by in vitro addition of a 0.03 microM concentration of rolipram. Because rolipram inhibited canine TNF production in vitro, a protocol was devised in which TNF inhibitory activity was measured in a series of blood samples from dogs infused with increasingly high doses of rolipram. This yielded the efficacy half of the therapeutic index, whereas the emetogenic dose represented the side effect portion of the index. Rolipram was infused stepwise into conscious dogs at gradually increasing doses. The infusion was stopped when vomiting occurred, and the cumulative dose was reported as the emetic dose. Rolipram caused emesis in dogs at a cumulative dose of 0.1 mg/kg. At each dose of rolipram, blood was collected. The whole blood was incubated in vitro with lipopolysaccharide to induce TNF production, which in turn was quantified by the L929 bio-assay. Theoretically, if the rolipram infusion raised blood values high enough, the rolipram in whole blood would inhibit TNF production and be reflected by a lack of TNF activity in the L929 assay. In this assay system, rolipram's 50% effective dose in the TNF assay was always at least 33-fold lower than its emetic dose of 0.1 mg/kg. This gave rolipram a therapeutic index of at least 33:1 (0.003 versus 0.1 mg/kg) on the basis of its activity in a canine efficacy model (TNF inhibition) and a toxicity model (emesis induction). Experimental compounds were tested for their emetic dose as well as TNF 50% effective dose, with the goal of obtaining a therapeutic index better than that of rolipram. Thus the coupling of cytokine activity with overt toxicity was used to arrive at the therapeutic index of a compound. The therapeutic index was used to rank compounds as to their efficacy/toxicity profile. This ranking was used to eliminate several anti-inflammatory compounds that had a therapeutic index less than that of rolipram.

Animals↗
PubMed1994

Kinetics and reversibility of thyrotropin-releasing hormone-stimulated guanine nucleotide exchange in membranes from GH4C1 cells.

To evaluate the role of thyrotropin-releasing hormone (TRH)-stimulated guanine nucleotide exchange in the biphasic cellular responses to TRH, we have examined the kinetics, reversibility, and inhibition by QC120 (an antiserum recognizing the carboxyl terminus of alpha q/11) of TRH-stimulated guanosine-5'-(alpha-[35S] thio)triphosphate ([35S]GTP alpha S) binding in membranes from GH4C1 cells. Enhanced binding of [35S]GTP alpha S stimulated by TRH was dose dependent and readily detectable within 8 sec of TRH treatment. Binding measured within the first 20 sec was largely inhibited by QC120, whereas additional binding that accumulated during incubations of 3-6 min was not inhibited by even high concentrations of the antiserum. TRH-stimulated binding was reversible, in that, after membranes were incubated with TRH and [35S]GTP alpha S, subsequent addition of excess GTP caused exchange of 70-100% of the prebound radioligand. Exchange of TRH-stimulated [35S]GTP alpha S binding occurred in fast and slow phases, with half-times of < 5 sec and 187 sec, respectively. Addition of QC120 before the GTP chase inhibited the fast phase of exchange, whereas reduction of the TRH concentration in the preincubation selectively reduced the magnitude of the slow phase. Neither phase of exchange was affected by prior treatment of cells with pertussis toxin. Our observations indicate that Gq/11 is rapidly activated by the TRH receptor and that a second, unidentified, G protein is slowly activated by the TRH receptor.

Amino Acid Sequence↗
PubMed1993

Developmental patterns of aluminum in mouse brain and effects of dietary aluminum excess on manganese deficiency.

Previous studies have shown that excess dietary Al during development can affect neurobehavioral measures and decrease tissue Mn of 21-day-old weanling mice without a corresponding increase in tissue Al concentrations. Al and Mn have similar tissue concentrations and similar affinities for transferrin, which is the major plasma transport protein for Al and Mn as well as Fe. In the present study, brain Al, Mn and Fe were studied at 6, 12, 18 and 24 days of age in offspring of Swiss Webster mice fed a semipurified diet containing excess Al (Al[+], 1000 micrograms Al/g diet, Al as Al lactate), marginal Mn (Mn[-], 3 micrograms Mn/g diet) or both excess Al and marginal Mn (Al[+]Mn[-]) from conception to day 24 postnatal (weaning on day 18). Brain Al concentrations were higher at 6 days of age than at later ages and were significantly elevated by the excess Al diet (P = 0.017) but returned to control levels by weaning. Brain Mn concentrations increased from day 6 to day 24 and were lower in the Mn deficient groups (P < 0.001) and also in the excess Al group (P = 0.024) than in controls. Brain Fe concentrations were not influenced by diet. Similar patterns were seen in liver as in brain. The marginal Mn diet led to postnatal growth retardation which was more severe in litters of dams fed Al[+]Mn[-] diets than in litters fed Mn[-] diet. These data suggest that excess Al in diet can interact specifically with Mn metabolism during development.

Aluminum↗
PubMed1993

Aluminum accumulation and neurotoxicity in Swiss-Webster mice after long-term dietary exposure to aluminum and citrate.

The present study was performed to determine aluminum uptake, retention, and neurotoxic effects in the presence of dietary citrate. Six-week-old female Swiss-Webster mice were fed semipurified diets containing 3.5% sodium citrate and either 3 micrograms Al/g diet (3 Al) or 1,000 micrograms Al/g diet (1,000 Al) as AlCl3. After 5 to 7 weeks of feeding these diets, changes in behavior were assessed using the National Institute of Environmental Health Sciences Neurobehavioral Test Battery. Liver and bone Al concentrations in the 1,000 Al group were higher than in the 3 Al group at both the 5- and 7-week time points. Spinal cord Al concentrations in the 1,000 Al group were 200% higher at 5 weeks (P < .01) than in controls, and brain nuclear fraction Al concentrations in the 1,000 Al group were 150% higher at 5 and 7 weeks (P < .01) than in the 3 Al group. The Neurobehavioral Test Battery showed lower grip strength and greater startle responsiveness in the 1,000 Al group compared with the 3 Al group at both the 5- and 7-week time points. Based on reports that Al can act as a pro-oxidant, we examined Al-induced brain lipid and protein oxidative damage; neither was evident in the Al-intoxicated mice. In summary, feeding of Al and citrate to mice resulted in Al accumulation in the central nervous system, and this accumulation was associated with overt signs of neurotoxicity. Brain protein and lipid oxidative damage was not associated with early manifestation of Al toxicity.

Aluminum↗