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Biomedical subjects

B Han

Publications and source records attributed to B Han.

At least 109 records · Page 6Linked to original sources

[The relationship between TIL from human primary hepatic carcinoma and prognosis].

OBJECTIVE: To determine whether tumor-infiltrating lymphocytes (TIL) could affect the prognosis for patients with primary hepatic carcinoma (PHC). METHODS: Tissue distribution, proliferative property and cytotoxicity of TIL were measured in colour medical image analysis, immunohistochemical technique, 3H-thymidine proliferative response and LDH-release assay. RESULTS: On the basis of infiltrating level of TIL, all patients with PHC were classified into three types in which there can be non-infiltrating, lower infiltrating and high infiltrating. The survival time of patients without TIL was shorter than that of patients with TIL. In addition, their postoperative intrahepatic recurrences were higher than those of the latter. Freshly isolated TIL showed more poor proliferation and cytotoxicity than autologous peripheral blood lymphocytes (PBL) in vitro. TIL activated with anti-CD3 McAb and rIL-2 displayed higher cytotoxicity against fresh autologous hepatic carcinoma cells than against K562 targets. CONCLUSION: Clinically, TIL are associated with the prognosis for patients with PHC, however, it is in the tumor nest that the functions of TIL are impaired or suppressed by some factors locally produced by tumor cells in vivo.

Adult↗

[Surgical treatment of extrahepatic bile duct carcinoma].

OBJECTIVE: To evaluate the experience in the diagnosis and surgical treatment of the extrahepatic bile duct carcinomas. METHODS: 242 patients with extrahepatic bile duct carcinoma over the past 20 years was retrospectively studied. RESULTS: The origin points were carcinomas of the upper bile duct in 168, of the middle bile duct in 18, and of the lower bile duct in 56 patients. The preoperative diagnostic rates for the location and the nature of the lesion were respectively raised to 97.2% and 94.5% by combination of ultrasonography and CT. The curative resection rates for the tumors in the upper, middle, and lower bile duct over the recent five years reached to 50.0%, 50.0% and 71.4%. respectively. Follow-up of patients with curative resection showed a one year recurrent rate of 73.9% and a three year recurrent rate of 100.0% with a mean recurrent time of 9.6 months in patients with local metastasis, in contrast to 13.3%, 71.4% and 17.5 months in those without metastasis. Metastasis was mainly responsible for the recurrence. Liver or multiple organ failure, intra-abdominal infection and gastrointestinal hemorrhage were the common and serious complications. CONCLUSION: The case number of the bile duct carcinoma presented a remarkable increment tendency. Ultrasonography and CT were satisfactory enough for diagnosis. To reduce the recurrent rate, resection of the tumor together with the lymph, nervous, fatty and connective tissues in the hepatic hilus, even the right celiac ganglia, should be considered the necessary procedure. Monitoring and protecting the main organs to prevent the multiple organ failure, controlling the gastrointestinal hemorrhage and the intra-abdominal infection are important to decreasing the mortality.

Adult↗

Iron and manganese uptake by offspring of lactating mice fed a high aluminum diet.

High dietary A1 can result in lowered tissue Mn and Fe concentrations in weanling mice. Possible mechanisms underlying this effect of A1 (altered milk Fe and Mn content, altered absorption or retention of Fe and Mn) were investigated in this experiment. To determine if milk composition was changed, milk was analyzed for Fe and Mn at 0, 3, 7, and 12 days postnatal. To determine if A1 influenced absorption and/or retention of Fe and Mn, a single milk meal containing 54Mn and 59Fe was administered by gavage to 12 day old pups and tissues were obtained 6 and 24 h later. Pup body and tissue weights were not affected by the high A1 diet. Milk from dams fed high A1 diets (1000 micrograms A1/g, n = 11, A11000) had similar Fe and Mn concentrations as milk from dams fed a control diet (7 micrograms A1/g, n = 11), although A1 concentrations were higher. Absorption and tissue distribution of 54Mn and 59Fe, as determined at the 6 h timepoint, were unaffected by maternal diet group (control n = 16, AL1000 n = 10). However, total retention of both 54Mn and 59Fe was 8-10% lower in the AL1000 pups 24 h after gavage (P = 0.030 for Mn and 0.017 for Fe). These data suggest that high dietary A1 during development alters the ability of nursing mouse pups to retain absorbed Fe and Mn.

Aluminum↗

Aluminum alters iron and manganese uptake and regulation of surface transferrin receptors in primary rat oligodendrocyte cultures.

Transferrin (Tf) is a major transport protein for both iron (Fe) and aluminum (Al), as well as manganese (Mn) and it can mediate cellular uptake of these elements via cell surface Tf receptors. To study the effect of Al-Tf on Tf receptor regulation, primary oligodendrocyte cultures were prepared from cortices of newborn rats. The effects of Al-Tf on 54Mn and 59Fe uptake were compared to those of apo-, Fe-, or Mn-Tf (1.25 microM). To examine changes in cell surface Tf binding capacity, preincubation (4 h, 37 degrees C) was performed with apo-, Al- or Fe-Tf and homologous receptor binding studies were subsequently conducted with 125I-Fe-Tf at 4 degrees C. Incubation with Al-Tf, but not with equimolar amounts of Al chloride or Al citrate, led to dose-related increases in cellular Al. Incubation with either Al- or Fe-Tf decreased 59Fe uptake, while incubation with either Al- or Mn-Tf decreased 54Mn uptake. Surface Tf receptor sites/cell were 1.05, 0.60 and 0.46 x 10(5) after incubations with equivalent amounts of apo-, Fe-, and Al-Tf respectively. The data suggest that Al-Tf down-regulates surface Tf receptors on oligodendrocytes and can limit Fe and Mn uptake through this mechanism.

Aluminum↗

Balloon angioplasty significantly increases collagen content but does not alter collagen subtype I/III ratios in the atherosclerotic rabbit iliac model.

Angioplasty has been reported to increase collagen content and to alter vascular collagen alpha 1(I), alpha 2(I), and alpha 1(III) mRNA levels. Collagen synthesis is tightly regulated by complex translational and post-translational mechanisms such that mRNA levels may not necessarily reflect biosynthesis. To test whether collagen subtype I and III protein levels are altered by angioplasty, we quantitatively analysed collagen I/III protein ratios at 4 weeks after balloon angioplasty. Twenty New Zealand White rabbits underwent iliac artery balloon de-endothelialization and then were placed on a 0.5% cholesterol/6% peanut oil diet for 7 weeks at which time angioplasty was performed on arteries with > or = 50% stenosis. Arteries with < 50% stenosis were not dilated and served as controls. Animals were killed 4 weeks later and hydroxyproline (OH-pro) content and subtype I/III ratios were analysed in 5-mm mid-iliac sections. OH-pro was measured by a colorimetric assay. Subtype ratios were determined by a highly quantitative two-dimensional cyanogen bromide peptide mapping method. The degree of stenosis was measured as the minimal vessel lumen diameter and calculated as a percentage stenosis compared to a proximal reference segment. Calculated collagen content (micrograms/mg tissue) was significantly higher 4 weeks following angioplasty compared to the non-dilated group (220.4 +/- 70.8 v 308.2 +/- 26.9, P = 0.04; n = 12), despite similar percentage stenosis in the primary and restenotic lesions. The ratio of collagen I/III subtype protein distribution was not significantly different in the non-dilated and angioplastied groups (4.88 +/- 1.00 v 4.70 +/- 0.82, respectively). These studies are the first to provide data on collagen I/III subtypes following angioplasty and suggest that collagen accumulation may be more important in restenosis than alteration of collagen protein subtypes.

Angioplasty, Balloon↗

Developmental patterns of aluminum and five essential mineral elements in the central nervous system of the fetal and infant guinea pig.

Al is found in the developing conceptus, but little information is available concerning its tissue distribution and its changes in concentration with age. Because Al has affinity for many of the same biological ligands as the essential mineral cations Ca, Mg, Zn, Fe, and Mn, we hypothesized that Al might show a pattern of developmental concentrations that was similar to one or more of these elements in the brain, a major target of Al toxicity. Concentrations of Al, Ca, Mg, Zn, Fe, and Mn were measured in spinal cord, brainstem, cerebellum, and forebrain of guinea pig fetuses on gestation day (GD) 30 and 45, at birth, and on postnatal day (PND) 3, 6, and 12. Dams were fed commercial guinea pig chow, which contained 47 micrograms Al/g. Tissue Al and Mn were measured with electrothermal atomic absorption spectrophotometry (ETAAS), and the other elements with inductively coupled axial plasma spectroscopy (ICAP-AES). Al concentrations in the brain regions were highest in spinal cord, brainstem, and cerebellum, and decreased during late gestation and lactation. Al did not show marked increases in regional brain concentrations during the final third of gestation as did Fe, Mg, and Zn. In contrast to Fe and Ca, Al did not accumulate in placenta. Al was the only element to show higher concentrations in spinal cord than in any other tissue at birth. In summary, the tissue distribution of Al did not follow that of essential cations as examined in this study.

Aluminum↗

Engineering, expression and renaturation of targeted TGF-beta fusion proteins.

This study reports the expression, purification, and renaturation of biologically active Transforming Growth Factor-beta 1 (TGF-beta 1) fusion proteins from Escherichia coli (E. coli). A prokaryotic expression vector was engineered to produce tripartite fusion proteins consisting of (i) a purification tag, (ii) a protease-sensitive linker/collagen binding domain, and (iii) a cDNA sequence encoding the active fragment of human TGF-beta 1. The expressed fusion proteins TGF-B1-F1 and TGF-B1-F2, located in inclusion bodies, were solubilized with 8 M urea and renatured using a glutathione redox-coupled system and protracted dialysis under several experimental conditions. The purification of the recombinant proteins was achieved by binding the His-tag of the fusion proteins on a Ni-NTA metal chelate column. The biological activity of the recombinant growth factor was demonstrated by its ability to inhibit mink lung (Mv1Lu) cell proliferation and/or to stimulate proliferation of NIH-3T3 mouse fibroblasts, where purified human platelet TGF-beta 1 served as a positive control. Purified TGF-B1-F1 and TGF-B1-F2 (collagen-binding) constructs exhibited anti-proliferative activities comparable to purified platelet TGF-beta 1, but at lower specific activities. Binding of the renatured TGF-B1-F2 fusion protein to collagen was demonstrated by stable binding on a collagen-conjugated Sephadex-G15 column. The high affinity binding was also demonstrated by the binding of 3H-collagen to the TGF-B1-F2 protein immobilized on a Ni-NTA column. The TGF-B1-F2 fusion protein bound to collagen coated surfaces with high affinity but exhibited comparatively lower biological activity than the fusion protein in solution, suggesting a potentially latent configuration. Taken together, these results demonstrate that biologically active TGF-beta 1 fusion proteins can be recovered from transformed bacteria by oxidative refolding; thus, providing a means for its high-yield production, purification, and renaturation from microorganisms. Furthermore, these results support the concept that auxiliary domains may be used to modulate and/or target TGF-beta 1 for specific applications.

3T3 Cells↗

[The role of urokinase type plasminogen activator in invasion of bile duct carcinoma].

OBJECTIVE: To study the role of urokinase type plasminogen activator (u-PA) in the invasive process of bile duct carcinoma. METHODS: The secretion of u-PA and the invasive potential of tumor cell in vitro in a newly established cell line of bile duct carcinoma, QBC939, were observed by using an amnion invasion culture system. RESULTS: QBC939 cells secreted u-PA with high invasive potential. The inhibitors of u-PA and plasmin, tranexamic acid and 6-aminocaproic acid, obviously inhibited the u-PA activity and the invasive potential of QBC939 cells. CONCLUSION: u-PA is one of the important enzymes in tumor invasion. Inhibiting u-PA or plasmin may be a prospective therapy for tumor treatment.

Bile Duct Neoplasms↗

[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↗

[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↗

[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↗

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↗

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↗

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↗