The prototype hypothesis and the origins of attachment working models: adult relationships with parents and romantic partners.
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Biomedical subjects
Publications and source records attributed to H Pan.
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PURPOSE: To investigate the occurrence, outcome and influencial factors of the peripheral anterior synechia (PAS) following implantation of posterior chamber intraocular lenses for finding a way to reduce the PAS. SUBJECTS: 40 eyes of 38 senile cataract patients with normal chamber angle and intraocular pressure (IOP) preoperatively were examined. METHODS: Extracapsular cataract extraction was performed under microscope with insertion of a posterior chamber lens implant vaulted anteriorly by 10 degrees. Gonioscopy and slit-lamp examination and photography of the operated eyes were performed 3 to 6 months postoperatively. RESULTS: PAS were found in 20 (50%) of the 40 eyes. Among the 20 eyes with PAS the locations of 23 haptics in 17 eyes corresponded with those of the PAS. PAS were seen more frequently with vertically sulcus-fixated haptics than with the horizontally capsular-fixated haptics, showing a significant difference (P < 0.05). 88% of the eyes with PAS had pupillary deformation, but their visual acuities and IOP were not affected. CONCLUSIONS: PAS is more likely to occur with vertically sulcus-fixated IOL. Rotating the capsular-fixated haptics to the horizontal position may reduce the incidence of PAS. Gonioscopy should be a routine follow-up examination.
Colorectal cancer was induced by subcutaneous injection of 1,2-dimethylhydrazine (DMH) in mice, and the animals were administered orally with 0.4% of tea polyphenols (TP) simultaneously for 20 weeks to study its preventive effects. Results showed incidence of colorectal cancer in mice administered with TP was significantly lower than in positive controls (P < 0.05), and average number of tumor foci and proportion of adenocarcinoma were significantly fewer in TP group than in positive controls (P < 0.01). Level of cytochrome P450 (CP450) in liver microsome of the mice administered with TP was lower than that both in negative and positive controls (P < 0.01), and activities of superoxide dismutase (SOD) in liver tissue were higher than those in positive controls (P < 0.01), but lower than in negative controls (P < 0.01). Proliferative index of epithelial cells in mice was not obviously influenced by TP. It suggested that TP could have preventive effects on experimental colorectal cancer with a possible mechanism of lowering CP450 and increasing the activity of SOD in the liver.
Tumor suppressor proteins are believed to play a role in regulating cell cycle control during mammalian development. The E6 and E7 oncoproteins from human papillomavirus type 16 are known to affect cell growth control, at least in part, through their inactivation of cellular tumor suppressor gene products, p53 and Rb, respectively. Therefore, these viral proteins can serve as trans-dominant repressors of tumor suppressor gene function. To study the potential role of p53 and Rb in murine lens morphogenesis, we generated transgenic mice in which the expression of E6 or E7 was directed to the developing lens. Transgenic mice expressing E7 exhibited microphthalmia and cataracts, whereas transgenic mice expressing E6 exhibited cataracts without noticeable microphthalmia. Microscopic analysis of the lenses from neonatal and adult E7 transgenic mice revealed inhibition of lens fiber cell differentiation, induction of cell proliferation in spatially inappropriate regions of the lens, and apoptosis. Transgenic mice expressing a mutant E7 that is defective in Rb/p107 binding exhibited normal eyes, suggesting that the activity of Rb and/or Rb-like proteins is required for the perturbation of lens development and induction of apoptosis in E7 mice. Microscopic analysis of lenses from E6 neonatal and adult transgenic mice indicated the presence of nuclei in elongated fiber cells, suggesting that E6 inhibits lens fiber cell denucleation. Furthermore, expression of E6 inhibited the apoptotic-like DNA degradation observed in the lenses of nontransgenic 15.5-day embryos. In lenses from neonatal E6 x E7 double transgenic mice, the level of apoptosis was reduced compared with that seen in lenses from neonatal E7 mice. In adults E6 x E7 double transgenic mice, lens tumors developed, whereas in E6 or E7 only transgenic mice, tumors did not. Taken together, these results point to specific roles in lens morphogenesis for Rb and p53 and to the necessity of these tumor suppressor gene products in regulating exit from the normal cell division cycle in differentiating lens fiber cells.
To define the mechanisms of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced transcription of the ornithine decarboxylase (ODC) gene, we isolated a genomic clone (hODC41B) of ODC from a human leukocyte genomic DNA library. The restriction endonuclease map, in comparison with the previously published sequences of the human ODC gene, indicated that hODC41B contained a 15.7-kb sequence that extended from the sixth exon to about 10 kb upstream of the ODC gene. A 2.5-kb genomic fragment containing the 5' flanking region and the first exon was subcloned and sequenced. Sequence analysis revealed multiple putative promoter/enhancer elements (a TATA box, a CAAT box, 17 GC boxes, and a cAMP-responsive element) but no consensus AP-1 sequences (TGAGTCA) in the 2.5-kb 5' flanking region. However, three AP-1 sequences were located in introns 3, 5, and 11. We constructed a series of chimeric genes containing part of the first exon and increasingly longer 5' flanking sequences of the ODC gene fused to either bacterial chloramphenicol acetyltransferase (CAT) or luciferase reporter genes. TPA inducibility was determined by transient transfection and measurement of CAT or luciferase expression in HeLa cells. The induction of CAT activity by TPA decreased with decreasing lengths of the 5' flanking sequences up to nt -82. The TPA induction from the construct -72 ODC CAT was threefold to sevenfold, and the TPA inducibility of the same fragment was about ninefold to 30-fold with the luciferase reporter gene. Further deletion analysis revealed TPA-responsive sequences in ODC nt -42 to +54. Gel mobility shift assays using alpha-32P-end labeled ODC nt -42 to +60 revealed that nt -42 to +60 specifically bound HeLa cell nuclear proteins. HeLa cell nuclear protein binding to ODC nt -42 to +60 could not be completely competed by AP-1-, AP-2-, AP-3-, or SP1-responsive sequences.
Interferon-gamma (IFN-gamma) is known to inhibit the growth of Toxoplasma gondii both in vivo and in vitro. The IFN-gamma induced anti-toxoplasma activity in human cells is strongly correlated with the degradation of the essential amino acid L-tryptophan in vitro. Destruction of L-tryptophan is due to an increased activity of indoleamine 2,3-dioxygenase (IDO), which is transcriptionally activated by IFN-gamma. To determine if indoleamine 2,3-dioxygenase alone is sufficient to block the T. gondii growth, we transfected human fibroblast cells with an IDO cDNA expression plasmid using a metallothionein-inducible promoter. We showed that IDO mRNA and its enzymatic activity are inducible in fibroblast cells transfected with right-orientation IDO cDNA upon addition of CdCl2 to culture medium. The elevated IDO enzyme activity is strongly correlated with an inhibition of T. gondii growth. No IDO mRNA nor enzyme activity is induced by CdCl2 in reverse orientation transfected cells, and no adverse effects were observed on T. gondii growth in cells transfected with the reverse IDO-construct or in control parent cells with or without supplementation of CdCl2. Our observations along with the recent report by Habara-Ohkubo et al. (Infect. Immun. 61, 1810-1813, 1993) suggest that IFN-gamma-induced antitoxoplasma activity is due at least in part to the activation of IDO gene.
At all ages XXX girls had significantly smaller head circumferences than control girls. Their IQ deficit was 24 points and IQ at age seven correlated significantly with head circumference at birth. In XXY boys, head circumference was significantly reduced at birth and up to nine years of age. The XXY boys' IQ deficit was 22 points, but IQ did not correlate with head circumference, as reductions in the two parameters did not always occur in tandem. The ratio of height-to-head circumference differed most in this group and could be useful in clinical recognition of this condition. XYY boys' head size did not differ from controls, despite their greater height, lower IQ scores indicating an adverse effect of an additional Y chromosome on brain development. The major factor affecting IQ outcome in the cohort was abnormal karyotype, with smaller effects from social class and head growth.
The actions of 5-hydroxtryptamine (5-HT)1A and 5-HT4 receptor agonists on fast excitatory postsynaptic potentials (EPSPs) in myenteric neurons of guinea pig ileum were studied in vitro. Intracellular electrophysiological methods were used to record EPSPs. 5-HT (0.1 microM), 5-carboxamidotryptamine (0.001-0.1 microM), 8-hydroxydipropylaminotetralin (0.003-0.3 microM), and 5-methoxytryptamine (5-MeOT; 0.3 microM) inhibited EPSPs. Agonist inhibition of EPSPs was blocked by the 5-HT1A receptor antagonists, spiperone and NAN-190. In the presence of NAN-190 (0.3 microM), 5-HT (0.001-0.1 microM) increased EPSP amplitude. 5-MeOT (0.001-0.1 microM), renzapride (0.01-0.3 microM), cisapride (0.01-1 microM), and BIMU 8 (0.003-0.1 microM) increased EPSP amplitude but did not change the membrane potential of any neuron. EPSP potentiation induced by each agonist was blocked by the 5-HT3/5-HT4 receptor antagonist, tropisetron (1 microM), but not by the 5-HT3 receptor antagonist, ondansetron (1 microM). Potentiation of fast EPSPs by 5-HT (0.1 microM) desensitized, whereas renzapride (0.1 microM) responses did not. Desensitization induced by BIMU 8 was variable. These data indicate that enteric 5-HT1A and 5-HT4 receptors function to inhibit and facilitate transmitter release, respectively. 5-HT4-mediated facilitation of ganglionic neurotransmission could contribute to the prokinetic effects of cisapride and renzapride.
It has been postulated that behavioural differences between normal males and those with an additional X or Y chromosome may be related to pre- or postnatal hormonal variations. The prenatal hormone status was investigated using amniotic fluid obtained at antenatal diagnosis between 16 and 20 weeks gestation from fetuses with sex chromosome abnormalities and from controls of the same gestational age. After log transformation, the (geometric) mean testosterone levels were XY 439.4 pmol/l, range 165-1,027 (n = 29), XYY 490.7 pmol/l, range 224-1,092 (n = 20); and XXY 419 pmol/l, range 87-1,021 (n = 20). There were no significant differences between the three male groups and all three were significantly higher than the XX fetuses at 147.0 pmol/l, range 41-474 (p < 0.001). These findings give no support to the hypothesis that prenatal testosterone levels contribute to later behavioural characteristics.
Using a combination of polymerase chain reaction and conventional cDNA library screening approaches, we have cloned and characterized a putative receptor tyrosine kinase termed tif. The extracellular domain of tif has an immunoglobulin-like loop and a fibronectin type III structure. The intracellular domain contains a tyrosine kinase domain. Compared with ryk, a ubiquitously expressed receptor tyrosine kinase, tif expression is tissue-specific with human ovary and testis containing the highest amount of tif mRNA. Many other tested human tissues such as heart, liver, pancreas and thymus do not contain detectable levels of tif mRNA. The molecular cloning and characterization of tif cDNA will facilitate the identification of a potential ligand(s) for the putative receptor and the study of its biological role.
Certain "high-risk" anogenital human papillomaviruses (HPVs) have been associated with the majority of human cervical carcinomas. In these cancers, two papillomaviral genes, E6 and E7, are commonly expressed. In this study we provide evidence that expression of the E6 and E7 genes from the high-risk HPV-16 in the skin of transgenic mice potentiated the development of preneoplastic lesions, and a high percentage of these epidermal lesions subsequently developed into locally invasive cancers. High levels of E6/E7 expression were found in these tumors relative to the preneoplastic lesions, and expression was localized to the proliferating, poorly differentiated epidermal cells. Also, the p53 and Rb genes were found to be intact, not mutationally inactivated, in representative skin tumors. These findings demonstrate that the E6 and E7 genes from a papillomavirus etiologically associated with human cervical cancer can contribute to the development of epidermal cancers in an animal model.
The oxygen transfer rates were investigated systematically in the CellCul-20A bioreactor with the device of cage aeration in this paper. The temperature, rotating speed, aeration rate and foam breaker, which affected the rate of oxygen transfer were studied, respectively. The mass transfer rate increased significantly with the aeration while the foam breaker had a negative effect on kLa, especially in a cell culture medium with 5% (v/v) calf serum. The oxygen transfer coefficients of surface and deep aerations were correlated, based on the experimental data.
The disposition of a single 20-mg oral dose of pravastatin was assessed in subjects with various degrees of renal function. Sixteen subjects (13 males, 3 females) with creatinine clearance values ranging from 15 to 112 mL/min/1.73 m2 completed the study. Area under the serum concentration-time curve, maximum serum concentration, time to maximum serum concentration, terminal serum elimination half-life, apparent clearance, and apparent volume of distribution for pravastatin were not affected by renal impairment, whereas the renal clearance of pravastatin decreased as creatinine clearance decreased (r2 = 0.697, P less than .001). The area under the serum concentration-time curve and time to maximum serum concentration of SQ 31,945 (a hepatic metabolite) increased in patients with renal impairment, whereas the terminal elimination rate constant and renal clearance of SQ 31,945 significantly decreased as a function of creatinine clearance. The renal clearance of another metabolite (SQ 31,906) also significantly declined with decreasing renal function. This single-dose study demonstrates that pravastatin pharmacokinetics were not affected in patients with renal impairment, probably because of its dual route of elimination.
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We have subjected the FLP protein of the 2-micron plasmid to partial proteolysis by proteinase K and have found that FLP can be digested into two major proteinase K-resistant peptides of 21 and 13 kDa, respectively. The 21-kDa peptide contains a site-specific DNA-binding domain that binds to the FLP recognition target (FRT) site with an affinity similar to that observed for the native FLP protein. This peptide can induce DNA bending upon binding to a DNA fragment containing the FRT site, but the angle of the bend (approximately 24 degrees) is smaller in magnitude than that induced by the native FLP protein (60 degrees). The additional DNA bending induced by the interaction between two native FLP molecules bound to the FRT site is not observed with the 21-kDa DNA-binding peptide. Amino-terminal sequencing has been used to map this peptide to an internal region of FLP that begins at residue Leu-148. It is likely that the DNA-binding peptide includes the catalytic site of the FLP protein.
Red blood cells from patients with paroxysmal nocturnal hemoglobinuria (PNH) were found to be liable to vesiculate, as demonstrated by both DMPC liposome- and CaCl2-induced vesiculation and measured in terms of acetylcholinesterase activity and 3H-inositol radioactivity in the supernatant. Membrane proteins released from the cells during vesiculation included several constituents with molecular weights identical to those of some complement regulating factors (e.g. DAF) which play an essential role in complement-mediated hemolysis. Red blood cells from both normal and PNH patients showed decreased deformability after vesiculation. Liability to vesiculate and the consequential loss of certain essential membrane proteins and decreased deformability might be a factor contributing to the mechanism of hemolysis in PNH.
H2O2 and hydroxyl free radical active oxygen generation systems were utilized to define the antioxidant activities of simple phenolic compounds derived from Chinese herbs. Although the antioxidant activities of compounds differed when assessed in the two systems, all compounds tested were found to be effective at preventing red blood cell membrane lipid peroxidation, with the propyl and butyl esters of gallic acid being especially potent. No compound was able to prevent hemoglobin oxidation. All compounds but salicylic acid were found to interact dose-dependently with H2O2 and hydroxyl free radical as determined by a chemiluminescence method.