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Biomedical subjects

S Li

Publications and source records attributed to S Li.

At least 1,315 records · Page 73Linked to original sources

Inhibitory effect of a steroidal antiestrogen (EM-170) on estrone-stimulated growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat.

Recently, compounds having pure antiestrogenic activity have become available. In this study, we examined the activity of the new steroidal antiestrogen EM-170 (N-n-butyl, N-methyl-11-(16' alpha-chloro-3',17' alpha-dihydroxy-estra-1',3',5'-(10')-trien-7' alpha-yl) undecanamide) on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma stimulated by treatment with estrone (E1), a steroid known to play an important role as precursor of 17 beta-estradiol (E2), especially in postmenopausal women. Twenty-five days after ovariectomy (OVX), tumor volume in control OVX animals decreased to 51.4 +/- 11% of the initial volume; treatment with E1, administered by Silastic implants, stimulated tumor growth to 179 +/- 21%. Treatment with the antiestrogen EM-170 at a dose of 200 micrograms (twice daily) not only completely reversed the stimulatory effect of E1, but also inhibited tumor growth to 30.5 +/- 9.6%, an effect that is 41% (P < 0.01 vs OVX control) greater than that of ovariectomy alone. At a relatively low dose of 40 micrograms (twice daily), 20 days of treatment with EM-170 reversed by 55% the stimulatory effect of E1 (1.0 micrograms, subcutaneously, twice daily) on tumor growth in OVX animals. On the other hand, the antiestrogen also induced a significant inhibitory effect on 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity in the DMBA-induced mammary tumors, an effect that is in agreement with the marked reduction caused by the same treatment on tumor estradiol (E2) levels in E1-treated OVX animals.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxysteroid Dehydrogenases↗

Vascular barrier-enhancing effect of an endogenous beta-adrenergic agonist.

Exogenous catecholamines have been proved to be active in the reduction of vascular permeability induced by various inflammatory mediators via beta-adrenoceptor activation, but it is not known whether an endogenous beta-adrenergic agonist has any effect. We studied it in skin and lung vessels. The results revealed that an intravenous bolus of isoproterenol (10 micrograms/kg) attenuated platelet-activating factor- and histamine-induced Evans blue dye extravasation in rat dorsal skin, while intraperitoneal administration of beta-adrenoceptor blocker propranolol (0.1 mg/kg) significantly increased the dye extravasation. Blockade of beta-adrenoceptor by propranolol for 12 h noticeably increased wet/dry lung weight ratio, lung water content, bronchoalveolar lavage (BAL) protein concentration, leukocyte count, and lipoperoxide degradation product malondialdehyde (MDA) content. In isolated perfused lung in vitro, propranolol (2.5 micrograms/ml) had no obvious effects on lung weight gain, fluid filtration coefficient, and pulmonary vascular pressure during the 20-min perfusion compared with control. The results suggested that endogenous beta-adrenergic agonist is an important factor in the maintenance of vascular integrity and the quiescent state of leukocytes, indicating the antiinflammatory role of catecholamines in physiological states and critical illnesses.

Adrenergic beta-Agonists↗

Side-chain oxysterol regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.

Side-chain oxysterols are known to be potent inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, a key regulatory enzyme in the biosynthesis of sterols. Structural variations in the side-chain oxysterols influence enzyme inhibition. Under certain conditions, biological systems have been induced to produce side-chain oxysterols, adding support to the hypothesis that oxysterols may be natural regulators of sterol biosynthesis in the intact cell. Specific inhibition of sterol biosynthesis is of interest as it may prove useful in the prevention or reversal of various cardiovascular disease states, as well as in the control of normal and abnormal cell growth.

Animals↗

Limitations of the standard linear solid model of intervertebral discs subject to prolonged loading and low-frequency vibration in axial compression.

The purpose of this study was to answer the following questions: (1) Can the standard linear solid model for viscoelastic material simulate the influence of disc level and degeneration on the ability of a disc to withstand prolonged loading and low-frequency vibration? (2) How well does the SLS model explain the relationship between the ability of a disc to resist prolonged loading and its ability to resist dynamic loads and dissipate energy when subjected to low-frequency vibration? Responses of human thoracic and lumbar discs were measured in axial compression under a constant load, and for cyclic deformations at three frequencies. Parameters of the SLS model for each disc were determined by a least-squares fit to the experimental creep response. The model was subsequently used to predict the disc's response to cyclic deformations. The SLS model was able to qualitatively simulate the effects of disc level and degeneration on the ability of an intervertebral disc to resist both prolonged loading and low-frequency vibration. However, the model underestimated the stress relaxation, dynamic modulus and hysteresis of thoracic and lumbar discs subjected to low-frequency vibration. The SLS model was unable to explain the relationship between the ability of a disc to resist prolonged loading and its ability to resist dynamic loads and dissipate energy when subjected to low-frequency vibration. Although in the lumbar discs the steady-state predictions of the SLS model were significantly correlated to the experimental response, the strength of model predictions decreased with increasing frequency, particularly for hysteresis.

Adult↗

Polymerase chain reaction determination of RhD blood type: an evaluation of accuracy.

OBJECTIVE: To evaluate the accuracy of polymerase chain reaction (PCR) amplification of a portion of the RhD gene by testing a large number of DNA samples derived from individuals whose RhD status was established by the standard serologic method. METHODS: Seven hundred sixty-five samples were obtained from two sources: subjects taking part in studies at the University of Iowa Hospitals and Clinics (n = 107), and Centre d'Etude du Polymorphisme Humain (CEPH) families used for studies of genetic variation (n = 658). Deoxyribonucleic acid was extracted from blood samples of University of Iowa volunteers and from CEPH families by standard techniques. With few modifications, published primers, reaction and electrophoresis conditions, which yield a 1200-bp fragment in all individuals and a 600-bp fragment in RhD-positive individuals, were used. RESULTS: By standard serologic techniques, we identified samples from 632 RhD-positive and 133 RhD-negative individuals. Two (both from CEPH) of the 632 RhD-positive individuals were characterized as RhD-negative by PCR. Seven of the 133 RhD-negative samples were judged to be RhD-positive by PCR because of the presence of a light 600-bp band. Despite repeated attempts, no bands or DNA were identified in one RhD-negative sample. Thus, the sensitivity of RhD typing by PCR was 99.7%, the specificity 94.0%. CONCLUSION: Based on our data, it would appear that the use of PCR to establish RhD type can be introduced cautiously into current management schemes in the evaluation of RhD sensitization.

Blood Grouping and Crossmatching↗

Hydrolytic degradation of devices based on poly(DL-lactic acid) size-dependence.

The hydrolytic degradation of aliphatic polyesters derived from lactic and glycolic acids (PLA/GA polymers) has been previously shown to proceed heterogeneously in the case of large size devices, the rate of degradation being greater inside than at the surface. A qualitative model based on diffusion-reaction phenomena was proposed which accounts for the formation of the more stable outer layer. However, this model also suggested that devices with dimensions smaller than the thickness of the outer layer should degrade less rapidly than larger ones. In an attempt to check this hypothesis, 15 x 10 x 2 mm compression moulded plates, millimetric beads and submillimetric microspheres and cast films, derived from the same batch of poly (DL-lactic acid) polymer were allowed to age comparatively in isoosmolar 0.13 M phosphate buffer, pH 7.4, at 37 degrees C. Ageing of the various devices was monitored by measuring water absorption, weight loss, L-lactic acid formation, pH and molar mass changes. As expected, large size plates and millimetric beads degraded heterogeneously and much faster than homogeneously degraded submillimetric films and particles.

Absorption↗

Involvement of serotonin in the regulation of GnRH gene expression in the male rat brain.

The role of serotonin (5-HT) in the regulation of the hypothalamo-pituitary-gonadal axis is still controversial. In order to evaluate the influence of 5-HT on gonadotropin-releasing hormone (GnRH) neurons, we have investigated the effects of repeated administration (during 2 days) of 5-HT, the 5-HT1+2 receptor antagonist methysergide, the 5-HT2 receptor antagonist ketanserin, and the 5-HT3 receptor antagonist ondansetron on GnRH mRNA levels in the male rat medial preoptic area (MPOA), as measured by quantitative in situ hybridization. The treatment with 5-HT decreased by 32% the number of silver grains overlying labelled neurons. The administration of methysergide and ketanserin increased the hybridization signal by 32% and 29%, respectively. On the other hand, the 5-HT3 receptor antagonist did not modify GnRH mRNA levels. The present results clearly indicate that the serotoninergic system exerts a negative tonic influence on the biosynthesis of GnRH as evaluated by mRNA level measurements. They also strongly suggest that the influence of 5-HT in the regulation of GnRH neuronal activity is mediated via activation of 5-HT2 receptor, although an involvement of 5-HT1 receptors cannot be totally excluded.

Animals↗

Efficacy of a live Cryptobia salmositica vaccine, and the mechanism of protection in vaccinated rainbow trout, Oncorhynchus mykiss, against cryptobiosis.

An attenuated strain of Cryptobia salmositica was used as a live vaccine to protect rainbow trout, Oncorhynchus mykiss, against cryptobiosis. Fish immunized with 1.0 x 10(4) or 5.5 x 10(4) attenuated C. salmositica per fish were protected 3 weeks after immunization; however, this period was reduced to 2 weeks if fish were vaccinated with 1.0 x 10(5) attenuated parasites per fish. Fish were still protected at 6, 12 and 24 months after vaccination. Complement fixing antibodies in the blood of immunized fish lysed C. salmositica under in vitro conditions. The titre of complement fixing antibodies in vaccinated fish increased rapidly 1-2 weeks post-challenge. In vitro phagocytosis was enhanced by antiserum and by activated macrophages from vaccinated fish. There was also evidence of antibody independent and antibody dependent cell-mediated cytotoxicity in vaccinated fish.

Animals↗

Hepatitis C virus RNA detection and HCV genotype in patients with chronic non-A, non-B hepatitis in Jakarta.

Antibody response in HCV infection may be variable and the variability of the serological response could be due to the differences in HCV strains. Since the distribution of hepatitis C virus genotype has been found to be geographically dependent, it is important to determine the distribution of HCV genotype in various countries with high prevalence of chronic non-A, non-B hepatitis. In this study, serum HCV RNA was examined in 53 patients suspected of chronic non-A, non-B hepatitis with an anti-HCV test as determined by currently available assay. HCV viremia was detected in 48 patients (90.6%). These patients had elevated serum ALT level at the time of HCV RNA determination. Using specific genotype probes, all isolates were classified into three different genotypes. Double and triple infections were also noted. HCV genotype 1b is the predominant genotype found in chronic hepatitis C patients in Jakarta.

Adult↗

Electroporation of influenza virus ribonucleoprotein complexes for rescue of the nucleoprotein and matrix genes.

Reverse genetics has been successfully used for the generation of recombinant influenza virus with altered biological properties. The standard method is based on DEAE-dextran transfection of in vitro reconstituted influenza virus ribonucleoprotein complex (RNP) into helper virus infected cells with subsequent selection of the recombinant viruses. Here we report the utilization of electroporation for reverse genetics of influenza virus as an improvement over the standard method. In a neuraminidase (NA) gene rescue system, we were able to demonstrate that electroporation of in vitro reconstituted NA RNP of influenza A/WSN/33 (H1N1) virus into WSN/HK virus infected cells allows the rescue of the transfectant WSN virus. The titer of transfectant virus obtained using electroporation is comparable to that generated using the DEAE-dextran transfection method. More significantly, the ratio of transfectant virus to helper virus is as much as 20-fold greater than that achieved using the DEAE-dextran system. We have also used electroporation to generate recombinant influenza virus carrying cDNA-derived matrix (M) gene or nucleoprotein (NP) gene of the WSN virus by using the temperature-sensitive (ts) mutants ts51 and ts56 as helper viruses. In the case of electroporation of M gene RNP, 88% of the viruses isolated after selection at 39 degrees C were transfectants. In contrast, the majority of viruses obtained using the DEAE-dextran transfection method were revertants of the helper virus. The NP-gene transfectant was only generated by the electroporation method. Our results suggest that electroporation of influenza virus RNP may be a useful method for generation of recombinant influenza viruses, especially in a system in which a ts mutant is used as helper virus.

Animals↗

Mutated K-ras gene analysis in a randomized trial of preoperative chemotherapy plus surgery versus surgery in stage IIIA non-small cell lung cancer.

The observation that the proteins encoded by ras genes play a central role in the signalling pathways used by cells to respond to growth factors and the fact that mutated ras proteins are constantly promoting cell division have led to a PCR-based hunt for additional clinical information. In the present study, K-ras analysis draws the following conclusions: (1) K-ras point mutation frequency was higher in the surgery group (10 of 24 patients) than in the chemotherapy-surgery group (3 of 20 patients). (2) Mutated K-ras was predominantly observed at codon 12 but five mutations appeared at codon 61. (3) Mutations were identified in the squamous cell carcinoma histological NSCLC subtype except in four cases corresponding to adenocarcinoma. (4) A multifarious pattern of substitutions, especially at codon 12, were noted with aspartic K 12 substitutions more prone to develop bone metastases. (5) Although a genotypic K-ras classification of NSCLC may not yet be formulated, our accumulated data (unpublished) suggest a trend toward it. (6) Patients with mutated K-ras tumors in the surgery group had no different survival than those with normal K-ras. However our pooled data as well as other authors' results assert that mutated K-ras constitute an additional prognostic datum that deserves to be included together with TNM classification. In the design of new preoperative (neoadjuvant) chemotherapy trials, stratification of tumors by K-ras status deserves to be further investigated in order to correlate with response, relapse and survival. Mutated K-ras genotype merits further research. Finally, the paradigm of uneven histological distribution and mutated K-ras spectra among researchers should serve as a stimulus to search for further contributions in this field.

Antineoplastic Combined Chemotherapy Protocols↗

Effects of dehydroepiandrosterone (DHEA) on GnRH gene expression in the rat brain as studied by in situ hybridization.

Dehydroepiandrosterone (DHEA) is an adrenal androgen that is converted into potent androgens and/or estrogens in peripheral tissues. To further investigate the potential role of DHEA in reproductive functions in the rat, we have studied the effect of 2-day administration of DHEA on GnRH gene expression in brain of sham-operated and castrated animals of both sexes. In the male rat, orchiectomy induced an increase in the hybridization signal. In sham-operated animals, DHEA decreased GnRH mRNA levels induced by orchiectomy. In orchiectomized rats, DHEA also depressed the amount of mRNA levels and then reversed the increase in mRNA levels induced by orchiectomy. In female animals, as observed in the male, castration produced an increase in the hybridization signal. In both sham-operated and ovariectomized animals, DHEA administration increased mRNA levels. These data clearly indicate that DHEA administration can modify neuronal GnRH gene expression in adult rats of both sexes, the effect being inhibitory in the male and stimulating in the female. This modulation of GnRH neuronal activity, which is probably exerted following the conversion of DHEA into active sex steroids, might be at least partly responsible for modifications of the activity of the hypothalamo-pituitary-gonadal axis induced by DHEA.

Animals↗

Failure of intrathymic inoculation of donor-specific splenocytes to prolong cardiac or renal allograft survival in dogs.

The intrathymic inoculation (ITI) of donor splenocytes into potential organ transplant recipients has been demonstrated to result in donor-specific unresponsiveness and greatly prolonged survival of subsequent organ allografts in rodents without the need for long-term pharmacological immunosuppressive therapy. We have studied the effect of the ITI of saline (controls) (groups 1 (n = 6) and 3 (n = 6)) or donor splenocytes (groups 2 (n = 10) and 4 (n = 8)) in dogs that received either pharmacological immunosuppression (with cyclosporine and prednisone, +/- azathioprine/cyclophosphamide) (groups 1 and 2) or rabbit anti-dog antithymocyte globulin (groups 3 and 4) at the time of ITI. Kidney or heart allografting (from the donor of the splenocytes) was carried out 16-74 days after ITI; all but four transplants were performed within 16-22 days after ITI. Mean kidney allograft survival was 6, 10, 9, and 9 days, respectively, in groups 1-4. Mean cardiac allograft survival was 7, 14, 8, and 7 days, respectively. There was no statistical difference in allograft survival between those dogs that received ITI of saline and those that received donor splenocytes. These results would suggest that the protocols developed to date using ITI in rodent species may not be successful in dogs.

Animals↗

Chemical pathways of peptide degradation. VIII. Oxidation of methionine in small model peptides by prooxidant/transition metal ion systems: influence of selective scavengers for reactive oxygen intermediates.

In the presence of oxygen, Fe(III), and an appropriate electron donor (e.g. ascorbic acid, dithiothreitol), the oxidation of methionine residues to methionine sulfoxides in small model peptides can be induced. It is shown in this study that these oxidations can be retarded by catalase in a pH-dependent manner, by some hydroxyl radical scavengers, and by azide. In contrast, superoxide dismutase has only a minimal effect, indicating that the superoxide radical does not contribute significantly to the oxidation of the methionine residue. The experimental results can be interpreted by invoking hydrogen peroxide as the major oxidizing species at pH < or = 7, whereas the involvement of free hydroxyl radicals seems to be negligible. Other reactive oxygen intermediates such as iron-bound hydroperoxy, or site-specifically generated reactive oxygen species may be actively involved in the oxidation of methionine residues at pH > 7.

Chromatography, High Pressure Liquid↗

An exploratory study of arm-reach reaction time and eye-hand coordination.

The study examined the time taken to reach and touch keys positioned both within and just outside the traditional reach envelope, as well as within and just outside the region of easy visibility, defined as being within a 30 degrees cone centered on the line of sight. Movements were required from a start key positioned in front of the subject to a response key positioned at one of 140 positions, defined by seven heights (from 360 to 1080 mm above the seat reference point (SRP), five angles (in vertical planes positioned from 30 degrees across the body to 90 degrees ipsilaterally) and four radii (from 200 mm closer to the body than the normal reach boundary to 100 mm further away than the normal reach boundary). The time taken was divided into detection time (the time from illumination of response signal to release of start key), and movement time (the time from release of start key to contact with response key). Results suggested that the visual cone should be extended downwards, as detection time increased rapidly to keys positioned outside the visual cone upwards, but not in the downwards direction. In general, responses to keys positioned anywhere that was both within the reach envelope and also within the visual cone took approximately the same time, from 371 to 420 ms. Movement time increased with distance moved, but disproportionately so, up to 595 ms, when movement was required to positions that were at one or more of the extremes of height, angle or radius.

Adolescent↗

Production and characterization of monoclonal antibodies against the recombinant p50csk protein tyrosine kinase: a tool for signal transduction research.

p50csk is a protein tyrosine kinase (PTK) that has been reported to regulate the activity of other PTKs belonging to the src gene family. Several hybridoma clones that produce monoclonal antibodies (MAbs) directed against recombinant p50csk were established. Five of the clones were analyzed for their ability to recognize native and denatured p50csk protein after undergoing native and denaturing polyacrylamide gel electrophoresis followed by western blotting. In addition, the clones were tested for their ability to immunoprecipitate p50csk and yet maintain tyrosine kinase activity of antibody-bound p50csk. None of the clones cross-reacted with pp60c-src, a PTK that shares with p50csk the homologous SH1 catalytic domain and SH2 and SH3 regulatory domains. These MAbs can be used to study p50csk directly, and its role in regulating members of the src family.

Animals↗

Perspectives on menopause.

Specific assumptions about knowledge lead directly to particular conceptualizations of menopause. The authors analyze the assumptions about menopause from biomedical, sociocultural, and feminist perspectives. In the process, how each perspective shapes research questions, research methodology, and interpretation of findings are discussed. The purpose of this article is to raise nurses' consciousness of consequences of basic philosophical assumptions on studies of menopause and knowledge generation.

Attitude to Health↗