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Biomedical subjects

D Lin

Publications and source records attributed to D Lin.

At least 145 records · Page 8Linked to original sources
PubMed1994

Induction of WAF1/CIP1 by a p53-independent pathway.

The p53-inducible gene WAF1/CIP1 encodes a M(r) 21,000 protein (p21) that has been shown to arrest cell growth by inhibition of cyclin-dependent kinases. Induction of WAF1/CIP1 in cells undergoing p53-dependent G1 arrest or apoptosis supports the idea that WAF1/CIP1 is a critical downstream effector of p53. In the present study, we used embryonic fibroblasts from p53 "knock-out" mice to demonstrate p53-independent induction of WAF1/CIP1. We show that serum or individual growth factors such as platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor but not insulin are able to induce WAF1/CIP1 in quiescent p53-deficient cells as well as in normal cells. The kinetics of this transient induction, which is enhanced by cycloheximide, demonstrates that WAF1/CIP1 is an immediate-early gene the transcript of which reaches a peak at approximately 2 h following serum or growth factor stimulation. On the other hand, DNA damage elicited by gamma-irradiation induces WAF1/CIP1 in normal human and mouse fibroblasts but does not affect WAF1/CIP1 expression in p53-deficient cells. These results suggest the existence of two separate pathways for the induction of WAF1/CIP1, a p53-dependent one activated by DNA damage and a p53-independent one activated by mitogens at the entry into the cell cycle. The possible function of p21 at this early stage is discussed.

3T3 Cells↗
PubMed1994

Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase.

A homozygous mutation in the kinase domain of ZAP-70, a T cell receptor-associated protein tyrosine kinase, produced a distinctive form of human severe combined immunodeficiency. Manifestations of this disorder included profound immunodeficiency, absence of peripheral CD8+ T cells, and abundant peripheral CD4+ T cells that were refractory to T cell receptor-mediated activation. These findings demonstrate that ZAP-70 is essential for human T cell function and suggest that CD4+ and CD8+ T cells depend on different intracellular signaling pathways to support their development or survival.

Alleles↗
PubMed1994

Characterization of a polyepoxy compound fixed porcine heart valve bioprosthesis.

Concerns with the currently available bioprostheses are calcification, long-term durability, and suboptimal hemodynamic performance. It is well known that these concerns are all more or less related to the cross-linking reagent, glutaraldehyde or formaldehyde, used in fixing bioprostheses. To address these concerns, we undertook the development of a porcine bioprosthesis fixed with a polyepoxy compound. In the development of this polyepoxy compound valve, it was found that the porcine leaflets fixed with polyepoxy compound were softer and more pliable than those fixed with glutaraldehyde. In this study, a special microtoming technique was developed to section the biological tissue so that the fixation uniformity in distinct layers of porcine aortic wall could be characterized. The fixation index and the denaturation temperature measurements in distinct layers of aortic walls showed that the cross-linking density was uniform throughout the entire aortic wall for the polyepoxy compound fixed porcine valve. It was also noted that the fixation index of the polyepoxy compound fixed aortic wall (91.5 +/- 0.5, n = 3) was not significantly different from that of its valvular leaflet (90.6 +/- 0.8, n = 3). Similarly, the denaturation temperature of the polyepoxy compound fixed aortic wall (80.4 +/- 0.9 degrees C, n = 5) was statistically comparable to that of its valvular leaflet (79.0 +/- 0.5 degrees C, n = 5). The results of this study indicated that polyepoxy compound can adequately fix the entire porcine aortic wall as well as its valvular leaflets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Fixation of bioprosthetic tissues with monofunctional and multifunctional polyepoxy compounds.

Collagen from a native tissue is fixed with a polyepoxy compound (PC) for use as a new biologic prosthetic material. Prior studies have shown that this biomaterial has comparable properties with collagen fixed with glutaraldehyde (GA), and thus has great promise for biomedical applications. A prior kinetic study indicated that the reaction between the functional groups of collagen and the multifunctional epoxy EX-313 is a 2.5th-order reaction. The purpose of this study was to understand the mechanism of the amino acid-PC reactions in a fixation process. Bovine arteries were fixed with a monofunctional PC (EX-131) and a multifunctional PC (EX-313) as a function of fixation time. A sequential fixation with a second fixative was used to identify the available remaining reactive sites from a prior fixation. The denaturation temperature (Td) was measured on each sample. Because the denaturation temperature is a direct indication of crosslinking of individual amino acids with the fixative, the increase in Td of a subsequent fixation may be indicative of the available remaining amino acids. The fixation index was measured on each sample to reflect the increase of fixation completion in a sequential fixation process. The fixation index and crosslink data also revealed that the reactive amino acids for EX-131 and EX-313 may not be exactly the same. The data in this study suggest that a monofunctional fixative can pre-react with the amino acids of collagen to effectively block further fixation of collagen with a second fixative. This amino acid masking may be associated with collagen branching. Collagen branching and its effect on denaturation temperature are described.

Animals↗
PubMed1994

Blood pressure changes and hormonal contraceptives.

The effects of low-estrogen and progestogen-only contraceptives on blood pressure changes were investigated on 238 women taking 35 micrograms EE OC, 267 using Norplant implants and 259 adopting IUD. The mean increases in diastolic pressure at 12, 24, 36 and 48 weeks among pill users were significantly (p < 0.05) higher than those among IUD users by 1.8, 2.1, 2.3 and 1.9 mm Hg, respectively; the increases in systolic pressure were higher but not significant (p > 0.05) by 1.3, 1.7, 1.5 and 1.3 mm Hg. Neither systolic nor diastolic blood pressure was affected by use of Norplant implants. Regression analysis, including interaction terms, showed that women's age, obesity and family history of hypertension were associated with an increase of blood pressure during follow-up and were independent of contraceptive use and vice versa. After adjustment of some potential confounding variables, pill users showed a 1.0 mm Hg rise in diastolic pressure, which is statistically significant but clinically unimportant.

Adult↗
PubMed1994

The effect of sequential compression devices on intraoperative blood loss during radical prostatectomy.

We reviewed 109 consecutive patients undergoing radical retropubic prostatectomy to determine the effect of intermittent pneumatic compression devices on intraoperative blood loss. Sequential compression devices were used intraoperatively and perioperatively in 86 patients, while 23 underwent surgery without these devices. There were no identifiable selection factors between the 2 groups. Median intraoperative blood loss was 885 cc without sequential compression devices and 800 cc when they were used. These results are at odds with previous reports in the urological literature and suggest that anatomical control of the dorsal vein complex negates any potential influence of sequential compression devices on blood loss during radical prostatectomy.

Bandages↗
PubMed1994

Modeling and mutagenesis of the active site of human P450c17.

Cytochrome P450c17 is the single enzyme having steroid 17 alpha-hydroxylase and 17,20 lyase activities. We sought to model the active site of this enzyme to identify residues contributing to its catalytic activities, and to test the roles of the identified amino acids by altering them via site-directed mutagenesis. Using the MIDAS-plus program, we modeled P450c17 and the structurally related steroid 21-hydroxylase, P450c21, on the crystallographically determined structure of bacterial P450cam. By positioning the progesterone substrate into each model, we identified five residues that appeared crucial for determining whether progesterone would undergo 17 alpha-hydroxylation (by P450c17) or 21-hydroxylation (by P450c21). Each identified residue in the P450c17 sequence was changed to the corresponding residue in the P450c21 sequence, yielding the four P450c17 mutants L102Y, G111D, G301l, and M369L + l371L. The mutants were transfected into COS-1 cells and their 17 alpha-hydroxylase, 17,20 lyase, and 21-hydroxylase activities were assayed by incubation with [14C]pregnenolone, [3H]17OH-pregnenolone, and [3H]17OH-progesterone and TLC. The L102Y and M369L + l371L mutants retained 50-80% of 17 alpha-hydroxylase and 70-100% of 17,20 lyase activity, while the G111D and G301l mutants lost both activities, but no mutants acquired detectable 21-hydroxylase activity (0.1% of wild type P450c21). Combination of the two mutants that retained partial activity (L102Y and M369L + l371L) yielded a single protein that retained 40% of 17 alpha-hydroxylase and 50% of 17,20 lyase activity, but none of the seven possible vectors expressing two, three, or all four of the mutations in a single enzyme yielded detectable 21-hydroxylase activity. The mutations D298V and D298S were predicted to ablate 17,20 lyase activity while retaining 17 alpha-hydroxylase activity, but were both inactive. These studies indicate that models based on the crystal structure of P450cam correctly predict many gross architectural features of steroidogenic enzymes and that many of the predicted residues are in or near the active site of P450c17. However, because enzymatic activity requires interactions between the enzyme and substrate at distances of less than 1 A, and modeling cannot predict atomic loci to greater than 1.5-2.0 A, it was not possible to design mutants that would confer 21-hydroxylase activity to P450c17. Currently available data cannot predict the structural and amino acid sequence requirements for a specific P450 activity.

Aldehyde-Lyases↗
PubMed1994

Analysis of 4-aminobiphenyl-DNA adducts in human urinary bladder and lung by alkaline hydrolysis and negative ion gas chromatography-mass spectrometry.

Analysis of carcinogen-DNA adducts has been regarded as a useful means of assessing human exposure to chemical carcinogens. We have established a method for quantitation of 4-aminobiphenyl (4-ABP)-DNA adducts by alkaline hydrolysis and gas chromatography with negative ion chemical ionization mass spectrometry (GC-NICI-MS). Aliquots of DNA (typically 100 micrograms/ml) were spiked with an internal standard, d9-4-ABP, and were hydrolyzed in 0.05 N NaOH at 130 degrees C overnight. The liberated 4-ABP was extracted with hexane and derivatized using pentafluoropropionic anhydride in trimethylamine for 30 min at room temperature prior to GC-NICI-MS. With in vitro [3H]N-hydroxy-4-ABP modified DNA standards, we observed 59 +/- 7% (n = 9) recovery of the 4-ABP and a linear correlation between hydrolyzed 4-ABP and the adduct levels ranging from about 1 in 10(8) to 1 in 10(4) nucleotides (r = 0.999, n = 9). The method was further validated by comparison of the results with that obtained by the 32P-postlabeling method. There was excellent agreement (r = 0.994, p < 0.001) between the two methods for quantitation of the adduct in eight samples of Salmonella typhimurium DNA treated with 4-ABP and rat liver S9, although the 32P-postlabeling method gave slightly higher values. The DNA adducts in 11 human lung and 8 urinary bladder mucosa specimens were then determined by our GC-NICI-MS method. The adduct levels were found to be < 0.32 to 49.5 adducts per 10(8) nucleotides in the lungs and < 0.32 to 3.94 adducts per 10(8) nucleotides in the bladder samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkalies↗
PubMed1994

A study on the discontinuation and failure of contraception among newly married couples in Shanghai.

The authors investigate contraceptive failure and discontinuation among newly married couples in Shanghai, China, with a focus on the questions, "What percentage of births is due to contraceptive failure? What socio-psychological and demographic characteristics of a couple are related to the discontinuation or failure of contraception? How do the continuation rate and failure rate of contraception among newly married couples reflect the acceptance and effectiveness of various forms of contraception?"

Asia↗
PubMed1994

[A method of measuring iris radius by computerized image analysis].

A new method of measuring the iris contour has been set up with a personal computer. The model of a parabolic curve, an approximate mimic iris contour curve, was traced to define the profile contour of the iris from a photograph. A radius measured from the apex of the curvature of the parabola, named iris radius (IR), was calculated by a computer to describe the degree of the curvature of the iris contour. The iris radius of 93 eyes of 68 cases with early pupillary block primary angle closure glaucoma were measured by this method. The results show that the mean iris radius of cases with glaucoma is shorter than that of the normal age matched controls (53 cases 106 eyes) and there is statistical significant difference (P < 0.01). This method of measurement can be an effective method to further study the early diagnosis and pathogenic mechanism of the pupillary block angle closure glaucoma.

Adult↗
PubMed1994

The carboxy-terminal serine 392 phosphorylation site of human p53 is not required for wild-type activities.

Wild-type p53 functions in the G1 DNA damage checkpoint pathway by activating gene transcription and preventing cell cycle progression. Others reported that mutation of the serine 386 codon in mouse p53 abolished its ability to suppress growth. Serine 386 of murine p53 and the homologous residue of human p53, serine 392, are phosphorylated in vivo and can be phosphorylated in vitro by casein kinase II (CKII). We constructed mutants that changed serine 392 of human p53 to alanine (p53-S392A) or aspartic acid (p53-S392D); cotransfection of both these mutants with a reporter gene carrying a p53-responsive element into the p53-null Saos-2 cell line activated transcription as well as did wild-type p53. Furthermore, both mutants blocked cell cycle progression after transient transfection in these cells. A stable derivative of the T98G human glioblastoma cell line was established that expressed p53-S392A in response to dexamethasone. Overexpression of this mutant activated transcription of the endogenous waf1 (also called cip1) and mdm2 genes to the same extent as wild-type p53 and also produced growth arrest. Finally, p53-S392A and p53-S392D suppressed foci formation by activated ras and adenovirus E1A oncogenes as efficiently as did wild-type p53. Thus, unlike mutants that altered the serine 15 phosphorylation site, elimination of the serine 392 phosphorylation site had no discernible effect on p53 function. We conclude that neither phosphorylation nor RNA attachment to serine 392 are required for human p53's ability to suppress cell growth or to activate transcription in vivo.

Adenovirus E1A Proteins↗
PubMed1994

[Facial nerve repairs: a comparative experimental study of epineural and perineural techniques].

This paper reports the comparative study results of perineural and epineural techniques in facial nerve (FN) transection injuries of 16 rabbits. We found little difference in recovery of FN function and histology between epineural and perineural repairs. Both epineural and perineural sutures on FN have not yet solved the problem of misdirection growth of nerve fibers. It is possible to cause the synkinesis movement by using epineural or perineural sutures in human FN. The epineural repair method should be used at the site of FN trunk which is present as a structure of mixed fasciolae giving out branches. The recovery degree of-eye-openings, ENoG and anastomotic pass-rate of regenerating myelinated axons could reflect the recovery degree of FN transection objectively. The three parameters show a parallel relationship. We suggest that either epineural suture or perineural suture should be carried out after FN transection injury.

Animals↗
PubMed1994

[Amplification of C-myc oncogene in squamous cell carcinoma of the larynx].

C-myc amplification in 22 squamous cell carcinomas and 10 normal tissues (control) from the larynx was assessed by dot hybridization technique. Significant amplification of C-myc oncogene was found in malignant tumours as compared with the normal tissues. The extent of amplification also correlated with advanced tumour stages. There was a significant increase in C-myc amplification in TNM stages III and IV when compared with the stages I and II. These data suggested that C-myc oncogene might be activated by gene amplification and it might have a key role in determining the aggressiveness of laryngeal carcinoma.

Carcinoma, Squamous Cell↗
PubMed1993

WAF1, a potential mediator of p53 tumor suppression.

The ability of p53 to activate transcription from specific sequences suggests that genes induced by p53 may mediate its biological role as a tumor suppressor. Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line. The WAF1 gene was localized to chromosome 6p21.2, and its sequence, structure, and activation by p53 was conserved in rodents. Introduction of WAF1 cDNA suppressed the growth of human brain, lung, and colon tumor cells in culture. Using a yeast enhancer trap, a p53-binding site was identified 2.4 kb upstream of WAF1 coding sequences. The WAF1 promoter, including this p53-binding site, conferred p53-dependent inducibility upon a heterologous reporter gene. These studies define a gene whose expression is directly induced by p53 and that could be an important mediator of p53-dependent tumor growth suppression.

Amino Acid Sequence↗
PubMed1993

Pulmonary function changes in children associated with fine particulate matter.

During winter months many neighborhoods in the Seattle metropolitan area are heavily affected by particulate matter from residential wood burning. A study was conducted to investigate the relationship between fine particulate matter and pulmonary function in young children. The subjects were 326 elementary school children, including 24 asthmatics, who lived in an area with high particulate concentrations predominantly from residential wood burning. FEV1 and FVC were measured before, during and after the 1988-1989 and 1989-1990 winter heating seasons. Fine particulate matter was assessed using a light-scattering instrument. Analysis of the relationship between light scattering and lung function indicated that an increase in particulate air pollution was associated with a decline in asthmatic children's pulmonary function. FEV1 and FVC in the asthmatic children dropped an average of 34 and 37 ml respectively for each 10(-4) m-1 increase in sigma sp. This sigma sp increase corresponds to an increase in PM2.5 of 20 micrograms/m3. It is concluded that fine particulate matter from wood burning is significantly associated with acute respiratory irritation in young asthmatic children.

Air Pollutants↗