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Biomedical subjects

E Chen

Publications and source records attributed to E Chen.

At least 163 records · Page 9Linked to original sources
PubMed1994

Population-wide mortality trends among patients hospitalized for acute myocardial infarction: the Ontario experience, 1981 to 1991.

OBJECTIVES: This study attempted to determine population-based trends in in-hospital patient fatality from acute myocardial infarction. BACKGROUND: The in-hospital prognosis for patients with acute myocardial infarction should be improving as a result of adoption of treatments proved in randomized trials (e.g., thrombolytic, beta-adrenergic blocking and anticoagulant agents and aspirin). However, all trials are subject to selection biases, eligibility is limited for some therapies, and proved therapies may be underused even among eligible patients. METHODS: Using administrative data from all general hospitals in Ontario, Canada, we analyzed 17,489, 17,839, 18,393, 18,794, 18,716 and 19,748 records of patients with a primary discharge diagnosis of myocardial infarction for fiscal years 1981, 1983, 1985, 1987, 1989 and 1991, respectively. RESULTS: After age and gender adjustment, the overall relative reduction in in-hospital case fatality rates for the 10-year period was 26.9% (99% confidence interval [CI] 26.8% to 26.9%), corresponding to an absolute reduction of 6% (99% CI 5.6% to 6.4%). Age- and gender-standardized case fatality rate decreased from 22.3% in 1981 to 21.4% in 1985, followed by a highly significant decline to 16.3% in 1991. On the basis of the relation of comparative mortality to days of hospital stay, declining mortality was not an artifact of decreasing length of stay. CONCLUSIONS: There have been encouraging improvements in survival after acute myocardial infarction over the past 6 years. Further improvements may require development of new therapies that can be more widely applied to this patient population.

Age Distribution↗
PubMed1994

Crystal structure at 1.9-A resolution of human immunodeficiency virus (HIV) II protease complexed with L-735,524, an orally bioavailable inhibitor of the HIV proteases.

L-735,524 is a potent, orally bioavailable inhibitor of human immunodeficiency virus (HIV) protease currently in a Phase II clinical trial. We report here the three-dimensional structure of L-735,524 complexed to HIV-2 protease at 1.9-A resolution, as well as the structure of the native HIV-2 protease at 2.5-A resolution. The structure of HIV-2 protease is found to be essentially identical to that of HIV-1 protease. In the crystal lattice of the HIV-2 protease complexed with L-735,524, the inhibitor is chelated to the active site of the homodimeric enzyme in one orientation. This feature allows an unambiguous assignment of protein-ligand interactions from the electron density map. Both Fourier and difference Fourier maps reveal clearly the closure of the flap domains of the protease upon L-735,524 binding. Specific interactions between the enzyme and the inhibitor include the hydroxy group of the hydroxyaminopentane amide moiety of L-735,524 ligating to the carboxyl groups of the essential Asp-25 and Asp-25' enzymic residues and the amide oxygens of the inhibitor hydrogen bonding to the backbone amide nitrogen of Ile-50 and Ile-50' via an intervening water molecule. A second bridging water molecule is found between the amide nitrogen N2 of L-735,524 and the carboxyl oxygen of Asp-29'. Although other hydrogen bonds also add to binding, an equally significant contribution to affinity arises from hydrophobic interactions between the protease and the inhibitor throughout the pseudo-symmetric S1/S1', S2/S2', and S3/S3' regions of the enzyme. Except for its pyridine ring, all lipophilic moieties (t-butyl, indanyl, benzyl, and piperidyl) of L-735,524 are rigidly defined in the active site.

Aspartic Acid Endopeptidases↗
PubMed1994

NF-kappa B/Rel family members are physically associated phosphoproteins.

We performed radioimmunoprecipitation followed by serial immunoblots to show that, in the unstimulated Jurkat T cell line, the NF-kappa B/Rel family proteins, p80-c-Rel, p105-NF-kappa B, p65-NF-kappa B, p50-NF-kappa B and p36-I kappa B alpha, can be detected as complexes using antisera against c-Rel, p105-NF-kappa B or p65-NF-kappa B. p36-I kappa B alpha and p105, both known inhibitors of NF-kappa B function, can physically associate with NF-kappa B/Rel family members, but not with each other. In vivo and in vitro phosphorylation experiments demonstrated that NF-kappa B/Rel family members, including p105, c-Rel, p50, p65 (for the first time for p50 and p65) and p36-I kappa B alpha are also phosphoproteins. Phosphoserine and phosphothreonine residues were identified in these proteins isolated from unstimulated Jurkat cells. Both unphosphorylated and hyperphosphorylated forms of p36-I kappa B alpha were found in the complexes, suggesting that hyperphosphorylated I kappa B alpha is still capable of associating with the NF-kappa B/Rel family members. After stimulation with phorbol 12-myristate 13-acetate and phytohaemagglutinin for 10 min, p105-NF-kappa B and p50-NF-kappa B, but not p36-I kappa B, were highly phosphorylated. Phosphopeptide mapping of p105 showed that phorbol ester/phytohaemagglutinin stimulation may change p105 phosphorylation qualitatively.

Animals↗
PubMed1994

Purification of active herpes simplex virus-1 protease expressed in Escherichia coli.

Assembly of viral capsids for replication of herpes simplex virus requires the proteolytic processing of the assembly protein ICP35. The protease responsible for this process is encoded within the 635-amino acid open reading frame of the UL26 gene of the virus. A simple purification scheme is given in this report for the native, mature form of the protease expressed in Escherichia coli. The scheme allows the preparation of milligram quantities of purified enzyme for elucidation of kinetic mechanism as well as for structural studies. Utilizing a 13-residue peptide substrate representing the natural cleavage site that releases the protease, kcat and Km values of the purified native enzyme are 2.0 min-1 and 0.88 mM, respectively. Thus, peptide cleavage is less efficient than reported for other viral proteases. The possibility exists that viral or cellular factors are involved in vivo for activation of the protease for herpes capsid maturation.

Amino Acid Sequence↗
PubMed1994

Regulation of amelogenin gene expression during tooth development.

The amelogenins are the predominant matrix proteins in developing enamel and are crucial for proper enamel mineralization. Transgenic mice were constructed in order to identify the segment of the amelogenin gene required for specific expression in enamel organ cells. A 3.5 kb fragment of the bovine X-chromosomal amelogenin gene that includes a TATA box, the transcription initiation site, and 32 bp of exon 1 was linked to the beta galactosidase gene and injected into fertilized mouse eggs. Newborn transgene positive mice expressed beta galactosidase activity in developing teeth treated with the chromogenic substrate Xgal. Foci of ameloblasts were positive in newborn mice; stain intensity and number of positive ameloblasts increased in 1-day and 2-day postnatal mice. Some of the adjacent stratum intermedium cells also were positive in the later stages. Targeting of the transgene to the enamel organ was specific; the only other cells observed to be positive were macrophages, which have endogenous beta galactosidase activity.

Ameloblasts↗
PubMed1994

Revascularization after acute myocardial infarction: impact of hospital teaching status and on-site invasive facilities.

OBJECTIVE: To investigate the influence of hospital teaching status and service availability on rates of revascularization following myocardial infarction. DESIGN: Retrospective cohort study based on province-wide hospital discharge abstracts. SETTING: All acute care hospitals in Ontario, Canada's most populous province (9.7 million). PATIENTS: Patients admitted to hospital between April 1, 1991, and September 30, 1991, with a principal diagnosis of acute myocardial infarction. MEASUREMENTS: The odds of a patient's having been referred for revascularization (angioplasty or bypass surgery) within six months of a myocardial infarction were calculated based on the type of hospital to which he or she had initially presented, defined as "teaching" or "nonteaching" or as having or not having interventional facilities on-site (cardiac catheterization and/or revascularization). Odds ratios were adjusted for potential confounding variables, and for possible joint effects of teaching status and on-site interventional capabilities. RESULTS: The patients were more likely to have had revascularization (OR 1.79; 95% CI 1.47-2.14, p = 0.0001) when they had been admitted to a teaching hospital, and independently were more likely to have been referred for revascularization (OR 1.34; 95% CI 1.09-1.66, p = 0.0067) when they had been admitted to a hospital with on-site interventional facilities. There was no interaction between teaching status and service availability regarding referral for revascularization. CONCLUSION: Teaching status is an important determinant of revascularization following acute myocardial infarction and is independent of service availability, which also influences revascularization rates.

Adult↗
PubMed1994

Determinants of low systemic vascular resistance during cardiopulmonary bypass.

Although low systemic vascular resistance occurs during normothermic and hypothermic cardiopulmonary bypass, the determinants of depressed systemic vascular resistance and its effect on outcomes are unknown. To assess the predictors and clinical effects of low systemic vascular resistance, 555 patients undergoing isolated coronary artery bypass grafting were evaluated prospectively. The extent of low systemic vascular resistance during bypass was estimated by the amount of the vasoconstrictor phenylephrine administered: group 1, 0 to 160 micrograms; group 2, 161 to 800 micrograms; group 3, more than 800 micrograms. Multivariate analysis identified bypass temperature, bypass time, and ventricular function as determinants of low systemic vascular resistance. Patients on normothermic bypass accounted for 65% of the patients in group 3 and only 34% of the patients in group 1 (p < 0.0001). The bypass time was longer in the patients in group 3 (97 +/- 28 minutes) than in the patients in group 1 (89 +/- 24 minutes; p < 0.006). Patients with a preoperative left ventricular ejection fraction of 0.40 or less required less phenylephrine during cardiopulmonary bypass (498 +/- 68 micrograms) than did patients with a fraction exceeding 0.40 (1,087 +/- 88 micrograms; p < 0.001). By multivariate analysis, advanced age and the presence of peripheral vascular disease were found to decrease the likelihood of low systemic vascular resistance during normothermic bypass. Diabetes, the left ventricular ejection fraction, the bypass time, and the total cardioplegia infused were found to influence the likelihood of low systemic vascular resistance during hypothermic bypass. Patients in group 3 had a higher cardiac index and lower-mean arterial pressure and systemic vascular resistance postoperatively. In those patients who received a left internal mammary artery graft, the incidences of the low-output syndrome (group 1, 4.9%; group 3, 2.7%; p = not significant) and myocardial infarction (group 1, 1.4%; group 3, 1.8%; p = not significant) were not influenced by the amount of phenylephrine infused during cardiopulmonary bypass. In those patients who were at high risk of suffering a stroke preoperatively, the hypotension induced by the low systemic vascular resistance and its treatment with phenylephrine was not associated with an increased incidence of stroke (group 1, 5.8%; group 3, 2.8%; p = not significant).

Aged↗
PubMed1994

Effects of pulsed ultrasound on the mouse neonate: hind limb paralysis and lung hemorrhage.

Exposure conditions were determined for hind limb paralysis and lung hemorrhage of neonatal mice due to pulsed exposure (10 microsecond pulse duration) to 1 MHz focused ultrasound. Spatial peak pulse average intensity and peak rarefactional pressure levels for paralysis in 50% of specimens sonicated were determined for pulse repetition frequencies of 1, 5 and 50 kHz at 10 degrees C and 2.4 s exposure duration. The results suggest that cavitation was involved in the paralysis at a pulse repetition frequency (PRF) of 50 kHz, but that cavitation took place in the coupling medium and probably not within the specimen during exposures at a PRF of 5 kHz. The results show an inverse relation between spatial peak pulse average intensity, or peak rarefactional pressure and sound on-time. Exposure conditions for lung hemorrhage were determined for a pulse duration of 10 microseconds at 10 degrees C and exposure durations of 2.4 and 180 s. The results show that the threshold exposure conditions for lung hemorrhage are much less than the conditions for cavitational or other effects reported for tissues that do not contain well defined gas bodies. In addition, the results show an inverse relation between exposure level and either exposure duration or sound on-time, suggesting that time is an important parameter associated with bubble effects.

Animals↗
PubMed1994

Who wants to eliminate heart disease?

Twenty-seven physicians and nine pharmacists at one University teaching hospital identified their preferred way of dying after attaining average life expectancy. Respondents' ranking of modes of dying showed high agreement (for physicians, W = 0.65, p < 10(-16)). Disease category, rapidity of death, and their interaction (ANOVA, all p < 0.0001) influenced choice. "Rapidly fatal cardiac death" was overwhelmingly preferred. Cancer and slowly fatal central nervous system disorders were rated last. Eliminating cardiovascular disease would necessarily increase the likelihood of other modes of death. If these respondents represent "informed consumers", then reducing cardiac death at normal life expectancy may be contrary to Western society's preferences.

Adult↗
PubMed1994

Spatial distribution of back scattering in the nuclear area of the non-cataractous human lens.

The spatial distribution of back scattering from a vertical cross-section of the nuclear area in non-cataractous human lens was investigated. The cross-section was centred on the pupil. There is no significant difference in average nuclear back scattering between sides. The distribution of back scattering along an axis perpendicular to the anatomical axis can be modelled as a second-order polynomial. It is believed that the increase of back scattering in the central region corresponds to the peak protein concentration in the centre of the nucleus. This information was obtained by imaging back scattering with Scheimpflug photography. The back scattering was measured photometrically in a 3 x 10 matrix of measuring areas within the lens nucleus. Each measuring area was 0.20 x 0.20 mm in size. It is anticipated that the established model will allow detection of nuclear cataract with high sensitivity, especially in early stages.

Aged↗
PubMed1994

A beta-galactosidase expression vector for promoter analysis.

An expression vector plasmid, designated pMCS beta gal, was constructed to contain a multiple cloning site for insertion of gene fragments with potential regulatory function. This plasmid was designed to test promoter activity in transgenic mice, since digestion with Pst I will release all vector sequences, which could inhibit transgene expression in vivo (Jaenisch, 1988). When this vector, containing the amelogenin promoter, was used to make transgenic mice, expression was tissue specific and developmentally regulated similar to the endogenous gene (Chen et al., 1994). In addition, the herpes simplex virus (HSV) thymidine kinase (TK) minimal promoter was inserted into pMCS beta gal to produce pTK beta gal, leaving an Sph I upstream site available for insertion of gene fragments with potential enhancer or silencer function, which can be assayed following transfection into cultured cells.

Animals↗
PubMed1994

Variation in hospital length of stay for acute myocardial infarction in Ontario, Canada.

Unexplained variation in length of stay (LOS) following acute myocardial infarction (AMI) has been observed among American hospitals. We explored this phenomenon in the universal hospital care system of Ontario, Canada's largest province, analyzing general hospital discharge abstracts for all patients with a primary diagnosis of AMI. Case homogeneity was increased by excluding inter-hospital transfers, in-hospital deaths, patients with revascularization during the index admission and patients with severe comorbid conditions. This left 11,411 records of patients in 187 hospitals from April 1, 1990 to March 31, 1991. The mean length of stay was 9.9 days with standard deviation of 3.8. Available patient and hospital characteristics explained only 12% of the individual variation in LOS. Interinstitutional variation remained highly significant after controlling for patients' characteristics within the 87 hospitals admitting more than 50 cases per annum; these hospitals accounted for 84% of the eligible provincial admissions. The grand mean length of stay for 87 hospitals was 10 days, ranging from 6.6 to 12.9 days. Stepwise multiple linear regression analyses showed that lower caseload was associated with an increased length of hospitalization. Thus, despite Ontario's uniform system of hospital funding and medical insurance, a large amount of unexplained variation in length of stay exists for patients hospitalized with AMI, affecting thousands of bed-days per annum.

Adult↗
PubMed1994

Trichothiodystrophy: clinical spectrum, central nervous system imaging, and biochemical characterization of two siblings.

Trichothiodystrophy (TTD), an autosomal recessive disorder characterized by sulfur-deficient brittle hair, identifies a group of genetic disorders with an altered synthesis of high-sulfur matrix proteins and a defect in excision repair of ultraviolet damage in fibroblasts of most TTD patients. In contrast to patients with xeroderma pigmentosum (XP), TTD patients do not have an increased frequency of skin cancers. TTD patients may be grouped into four categories: 1) those without photosensitivity and without a defect in excision repair of UV damage; 2) those without photosensitivity and with an excision-repair defect in the same gene as in XP-D (complementation group D); 3) those with photosensitivity and with the XP-D repair defect; 4) those with photosensitivity and with a repair defect distinct from that in XP-D. We present a brother and sister in the third category of TTD. Clinically, the patients have brittle hair, short stature, ichthyosis, photosensitivity, nail and dental dysplasias, cataracts, mental retardation, and pyramidal tract abnormalities. Diagnosis was made by hair mount, which shows the characteristic banding pattern with polarizing microscopy, and by hair amino acid analysis, which demonstrated decreased high-sulfur matrix proteins. Fibroblasts cultured from skin biopsies had a marked DNA excision repair defect similar to the repair defect seen in XP-D. We have documented a unique dysmyelinating disorder on magnetic resonance imaging of the brain that might explain their mental retardation, marked hyperactivity, and neurologic deficits. Following the discovery that the human excision repair cross complementing rodent ultraviolet group 2 (ERCC2) gene is able to correct the ultraviolet sensitivity of XP-D cell strains, the ERCC2 cDNA from previous TTD patients was sequenced and shows frameshifts, deletions and point mutations in the ERCC2 gene. Molecular analysis of our patients is in progress. Molecular analysis of the defects in ERCC2 in clinically distinct patients with XP,XP/Cockayne's syndrome, and TTD may provide insight into the molecular mechanisms of these genetically related but clinically distinct disorders.

Brain↗
PubMed1994

Hysterectomies. Where are the indications?

This article reviews the major reasons for hysterectomies and critiques some of the alternative practices, such as medical therapy to shrink fibroids, and new surgical techniques, such as laparoscopic-assisted hysterectomies. Perhaps in response to the increased attention and the new procedures and drugs that allow more conservative management, the rate of hysterectomies has actually decreased.

Demography↗
PubMed1993

Referral adherence in an inner city breast and cervical cancer screening program.

BACKGROUND: Early detection and immediate follow-up treatment for cancer of the breast and cervix can reduce morbidity and mortality. This report describes adherence to follow-up appointments for suspected breast and cervical malignancies in a population of low-income black women who participated in a community-based nurse-managed screening program. METHODS: Components of the program that were part of the intervention included the following: a consistent referral mechanism augmented by a computerized tickler system; education of women about the importance of follow-up; and active nurse assistance in the follow-up process. Referral for follow-up of suspected malignancies or for other questionable findings was made to the public sector hospital clinics (86%) or to other providers of the women's choice (14%). RESULTS: Follow-up rates for suspected malignancies of the breast were high (92%) in this population of women, sometimes described as less likely to adhere to recommendations for continued care. In contrast, adherence rates for gynecologic conditions were lower (70%). CONCLUSIONS: This screening program and follow-up system has relevance to systems that serve similar groups of low-income women.

Adult↗
PubMed1993

Simpson-Golabi-Behmel syndrome: congenital diaphragmatic hernia and radiologic findings in two patients and follow-up of a previously reported case.

This report suggests the association of congenital diaphragmatic hernia in Simpson-Golabi-Behmel syndrome by describing two unrelated males with this malformation. One male was the maternal half-nephew of our previously reported 8-year-old boy with this syndrome. Review of the skeletal roentgenograms of these 2 affected males, and those of the previously reported 8-year-old, documents flare of the iliac wings, narrow sacroiliac notches, and the presence of two carpal ossification centers as a newborn ("advanced bone age"). We also report the follow-up of the 8-year-old boy, now 16 years old, who continues to have significant overgrowth and speech, dental, developmental, and adjustment problems.

Abnormalities, Multiple↗