Biomedical subjects

S C Lin

Publications and source records attributed to S C Lin.

At least 91 records · Page 5Linked to original sources

PubMed1998

The ability of CD40L, but not lipopolysaccharide, to initiate immunoglobulin switching to immunoglobulin G1 is explained by differential induction of NF-kappaB/Rel proteins.

Antibodies of the immunoglobulin G1 class are induced in mice by T-cell-dependent antigens but not by lipopolysaccharide (LPS). CD40 engagement contributes to this preferential isotype production by activating NF-kappaB/Rel to induce germ line gamma1 transcripts, which are essential for class switch recombination. Although LPS also activates NF-kappaB, it poorly induces germ line gamma1 transcripts. Western blot analyses show that CD40 ligand (CD40L) induces all NF-kappaB/Rel proteins, whereas LPS activates predominantly p50 and c-Rel. Electrophoretic mobility shift assays show that in CD40L-treated cells, p50-RelA and p50-RelB dimers are the major NF-kappaB complexes binding to the germ line gamma1 promoter, whereas in LPS-treated cells, p50-c-Rel and p50-p50 dimers are the major binding complexes. Transfection of expression plasmids for NF-kappaB/Rel fusion proteins (forced dimers) indicates that p50-RelA and p50-RelB dimers activate the germ line gamma1 promoter and that p50-c-Rel and p50-p50 dimers inhibit this activation by competitively binding to the promoter without activating the promoter. Therefore, germ line gamma1 transcription depends on the composition of NF-kappaB/Rel proteins.

Animals↗

PubMed1998

Effect of pramipexole in treatment of resistant restless legs syndrome.

OBJECTIVE: To report the results of an open-label trial with a dopaminergic agent, pramipexole, in patients with treatment-resistant restless legs syndrome (RLS). MATERIAL AND METHODS: We studied the response to pramipexole in a consecutive series of 16 patients with symptomatic RLS who had previously experienced failure with other dopaminergic therapies. Patients assessed their posttreatment change in symptoms of RLS on a visual analog scale and indicated drug-related side effects with use of a checklist. RESULTS: With a mean dose of pramipexole of 0.3 mg, most patients reported clinically significant improvement. From 2 to 3 months after initiation of pramipexole therapy, nocturnal leg restlessness, involuntary leg movements, and insomnia had decreased in 12, 10, and 11 patients, respectively. The most frequent adverse effects were fatigue and stiffness, which occurred in a third of the patients. Overall, the drug was well tolerated. CONCLUSION: On the basis of these findings, we propose that pramipexole, a D2 subgroup receptor agonist, is an effective agent for treatment of RLS.

Adult↗

PubMed1998

A patient with familial Takayasu's arteritis presenting with fever of unknown origin.

Takayasu's arteritis rarely presents with fever of unknown origin. We describe a 14-year-old girl who was admitted with a 2-month history of fever of unknown origin associated with vague pain in her left upper arm. The constitutional symptoms responded to a trial of steroid therapy for suspected collagen-vascular disease, but flared up when the dose was tapered. An asymmetric radial pulse was recognized incidentally during follow-up examination; diagnosis of Takayasu's arteritis was confirmed by Duplex ultrasonography and angiography. Takayasu's arteritis must be considered when evaluating children with fever of unknown origin, especially those with a positive family history. Careful assessment of the peripheral vascular system with better interpretation of limb symptoms should allow early, appropriate treatment to prevent irreversible vascular damage.

Adolescent↗

PubMed1997

Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow.

Both estrogen and androgen exert their antiosteoporotic effects, at least in part, by inhibiting IL-6 production, thereby suppressing osteoclastogenesis. Several observations, however, suggest that besides increased IL-6 production, sensitivity of the osteoclastogenic process to this cytokine is altered after ovariectomy. Based on this and evidence that the ligand-binding subunit of the IL-6 receptor (gp80) is a limiting factor for the actions of IL-6 on bone, we hypothesized that sex steroids regulate expression of the IL-6 receptor as well. We report that 17beta-estradiol or dihydrotestosterone in vitro decreased the abundance of the gp80 mRNA as well as the mRNA of the signal-transducing subunit of the IL-6 receptor (gp130) in cells of the bone marrow stromal/osteoblastic lineage, and also decreased gp130 protein levels. These effects did not require new protein synthesis. In contrast to sex steroids, parathyroid hormone stimulated gp130 expression; this effect was opposed by sex steroids. Consistent with these findings, ovariectomy in mice caused an increase in expression of gp80, gp130, and IL-6 mRNAs in ex vivo bone marrow cell cultures as determined by quantitative reverse transcription (RT)-PCR, and confirmed on an individual cell basis using in situ RT-PCR. The demonstration of increased expression of the IL-6 receptor after loss of sex steroids provides an explanation for why IL-6 is important for skeletal homeostasis in the sex steroid-deficient, but not replete, state.

Animals↗

PubMed1997

Molecular characterization of the cyclin-dependent kinase inhibitor p27 promoter.

p27Kip1 is a member of the family of cyclin-dependent kinase inhibitors (CKIs), which play critical roles in the regulation of cell cycle. To study the transcriptional regulation that controls the expression of p27, we have isolated the p27 promoter, defined its transcription initiation site, and performed various analyses for sequences upstream to 3 kb. Transient transfection assays using fusion reporters containing progressively truncated p27 promoter fragments showed that a region of 170 bp upstream of the start site is sufficient for maximal transcription activity. Detailed sequence analysis of this 170 bp region identified several GC-rich segments, putative sites of the transcription factor Sp1. Footprinting experiments revealed two Sp1-protected boxes, named BoxI and BoxII, which are located at positions -133 to -117 and -87 to -72, respectively. Binding of Sp1 to the two boxes was further demonstrated by gel mobility shift assays and supershift assays. Co-transfection studies in Drosophila Schneider line 2 cells showed that Sp1 indeed activates the p27 promoter constructs that harbor one or both of the GC-rich sequences. Furthermore, the GC-rich sequences could confer Sp1-dependent transactivation to a heterologous prolactin minimal promoter. Mutations in the GC-rich sequences abolished both binding and transactivation by Sp1. Taken together, our data strongly show that the p27 promoter is activated by the ubiquitously expressed transcription factor Sp1, which may provide a molecular mechanism for the constitutive nature of p27 transcription.

Animals↗

PubMed1997

Characterization of a novel mammalian RGS protein that binds to Galpha proteins and inhibits pheromone signaling in yeast.

Genetic studies of molecules that negatively regulate G-coupled receptor functions have led to the identification of a large gene family with an evolutionarily conserved domain, termed the RGS domain. It is now understood that RGS proteins serve as GTPase-activating proteins for subfamilies of the heterotrimeric G-proteins. We have isolated from mouse pituitary a full-length cDNA clone encoding a novel member of the RGS protein family, termed RGS16, as well as the full-length cDNA of mRGS5 and mRGS2. Tissue distribution analysis shows that the novel RGS16 is predominantly expressed in liver and pituitary, and that RGS5 is preferentially expressed in heart and skeletal muscle. In contrast, RGS2 is widely expressed. Genetic analysis using the pheromone response halo assay and FUS1 gene induction assay show that overexpression of the RGS16 gene dramatically inhibits yeast response to alpha-factor, whereas neither RGS2 nor RGS5 has any discernible effect on pheromone sensitivity, pointing to a possible functional diversity among RGS proteins. In vitro binding assays reveal that RGS5 and RGS16 bind to Galphai and Galphao subunits of heterotrimeric G-proteins, but not to Galphas. Based on mutational analysis of the conserved residues in the RGS domain, we suggest that the G-protein binding and GTPase-activating protein activity may involve distinct functional structures of the RGS proteins, indicating that RGS proteins may exert a dual function in the attenuation of signaling via G-coupled receptors.

Amino Acid Sequence↗

PubMed1997

Protein kinase C inhibits adenylyl cyclase type VI activity during desensitization of the A2a-adenosine receptor-mediated cAMP response.

We have previously reported that phosphorylation of adenylyl cyclase type VI (AC6) may result in the suppression of adenylyl cyclase activity during desensitization of the A2a-adenosine receptor-mediated cAMP response (A2a desensitization) in rat pheochromocytoma PC12 cells. In the present study, we demonstrate that protein kinase C (PKC) is responsible for the phosphorylation and inhibition of AC6 during A2a desensitization. Inhibition of PKC by several independent methods markedly blocked the suppression of AC6 during A2a desensitization. Purified PKC from rat brain directly phosphorylated and inhibited recombinant AC6 expressed in Sf21 cells. Substantially lower AC6 activities were also observed in PC12 cells overexpressing PKCdelta or PKCepsilon. Stimulation of A2a-R in PC12 cells under the same conditions as those required for A2a desensitization resulted in an increase in Ca2+-independent PKC activity. Most importantly, exogenous PKC did not further suppress AC6 activity in A2a-desensitized membranes. In vitro PKC phosphorylation of AC6 isolated from A2a-desensitized cells was also profoundly lower than that from control cells, suggesting a specific role for PKC in regulating AC6 during A2a desensitization in PC12 cells. Taken together, our data demonstrate that a calcium-independent, novel PKC inhibits AC6 activity during A2a desensitization in PC12 cells. Independent regulation of AC6 by calcium-independent PKC and by Ca2+ provides an exquisite mechanism for integrating signaling pathways to fine-tune cAMP synthesis.

Adenylyl Cyclases↗

PubMed1997

Developmental regulation of the Drosophila Tropomyosin I (TmI) gene is controlled by a muscle activator enhancer region that contains multiple cis-elements and binding sites for multiple proteins.

Developmental gene regulation in vertebrate somatic muscles involves the cooperative interaction of MEF2 (myocyte-specific enhancer-binding factor 2) and members of the b-HLH (basic helix-loop-helix) family of myogenic factors. Until recently, however, nothing was know about the factors that control the developmental regulation of muscle genes during embryogenesis in Drosophila. The Drosophila Tropomyosin I (TmI) gene contains a proximal and distal muscle enhancer within the first intron that regulates its expression in embryonic/larval and adult muscles. We have recently shown that the 355-bp proximal enhancer contains a binding site for the Drosophila homologue of vertebrate MEF2 and that MEF2 acts cooperatively with a basal level muscle activator region to direct high level muscle expression in transgenic flies. The 92-bp muscle activator region, however, does not contain any consensus E-box (CANNTG) binding site sequences for b-HLH myogenic factors, suggesting the MEF2 may interact with other factors to regulate muscle genes in Drosophila. In this study we have used mutation analysis and germ-line transformation to analyze cis-acting elements within the muscle activator region that regulate its expression in transgenic flies. We have identified a 71-bp region that is sufficient for low basal level temporal- and muscle-specific expression in the embryo, larva, and adult. Substitution mutations within the muscle activator region have identified several cis-element regions spanning 60-bp that are required for either full or partial muscle activator function. An analysis of proteins that bind to this region by gel mobility shift assay and copper nuclease footprinting has allowed us to identify the sites in this region at which multiple proteins complex and interact. We propose that these cis-elements and the proteins that they bind regulate muscle activator function and together with MEF2 are capable of regulating high level muscle expression.

Animals↗

PubMed1997

Endoscopic photocoagulation of the ciliary body for treatment of refractory glaucomas.

PURPOSE: To evaluate the safety and efficacy of endoscopic cyclophotocoagulation in the treatment of refractory glaucomas. METHODS: The preoperative and postoperative courses of 68 eyes of 68 patients who underwent endoscopic cyclophotocoagulation at our institution were retrospectively reviewed. Study patients had diverse forms of glaucoma, and most had failed maximal medical therapy as well as failed filtration or transscleral cyclodestructive procedures, or both. Endoscopic cyclophotocoagulation treatment encompassed 180 to 360 degrees of the ciliary body circumference and was performed through a limbal incision (56 eyes, 12 of which underwent concurrent cataract extraction) or pars plana incision (12 eyes). A second laser treatment was required in five eyes (7%). RESULTS: During the mean follow-up period of 12.9 months, mean +/- SD intraocular pressure decreased from 27.7 +/- 10.3 mm Hg preoperatively to 17.0 +/- 6.7 mm Hg at the final postoperative visit (P < .0001), for a mean reduction of 10.7 mm Hg and a mean percent decrease of 34%. Sixty-one eyes (90%) achieved an intraocular pressure < or = 21 mm Hg. Using this definition of success, Kaplan-Meier analysis predicted a successful outcome in 94% of patients after 1 year and 82% after 2 years. The mean number of glaucoma medications used by each patient was reduced from 3.0 +/- 1.3 preoperatively to 2.0 +/- 1.3 postoperatively (P < .0001). Best-corrected visual acuity was stable or improved in 64 eyes (94%), with four (6%) losing 2 or more lines of Snellen acuity. No case of hypotony (intraocular pressure < 5 mm Hg) or phthisis was observed. CONCLUSION: These early results suggest that endoscopic cyclophotocoagulation is a safe and effective therapeutic modality for refractory glaucomas.

Adolescent↗

PubMed1997

Replantation of part of an ear as an open fan composite graft.

A total amputation of the superior part of an ear with associated avulsion of adjacent scalp was treated successfully with a 'fan' technique, in which we unfolded the posterior skin envelope from the amputated ear segment and spread it onto part of the scalp defect of the temporal region. This resulted in a large area of contact between the composite graft and its recipient bed, with the added bonus of covering up some of the scalp defect. The remaining defect of the scalp was grafted with part of the avulsed scalp.

Adult↗

PubMed1997

Male/female differences in drug-induced emesis and motion sickness in Suncus murinus.

In order to elucidate possible male/female differences in emesis, the effects of various emetogenic drugs (cisplatin, copper sulfate, veratrine, nicotine, serotonin) and motion stimulus were compared between male and female Suncus murinus. Cisplatin (IP), nicotine (SC), veratrine (SC) and copper sulfate (PO) induced dose-dependent emesis in either sex, and there was no apparent difference in estimated ED50 values. However, male animals tended to be more susceptible to serotonin-induced emesis. The ID50 values for tropisetron, a 5-HT3 receptor antagonist, to block serotonin-induced emesis were also similar between male and female animals. However, tropisetron was less effective against cisplatin-induced emesis in females. Therefore, cisplatin may release more serotonin to induce emesis in females. Reciprocal shaking (horizontal oscillation 40 mm, frequency 0.5 to 2.0 Hz, duration 5 min) induced more frequent emesis in male animals, and the latency to the first vomit was shorter in males than in females. These results suggest that there is substantial sex-dependent difference in the emetic responses and male animals are in general more susceptible. These results are discussed in the light of similar studies in man.

Animals↗

PubMed1997

Assessing sleep in psychiatric inpatients: nurse and patient reports versus wrist actigraphy.

This study was designed to evaluate the conventional techniques of assessing sleep, nursing and patient report, of inpatients on a clinical psychiatric unit. Nurses assessed sleep/wake status at hourly checks and patients completed a sleep diary. For three nights patients wore a wrist actigraph, a portable instrument which provides objective data about sleep/wake activity. The nursing and patient data obtained were compared with actigraphy data. Nursing staff evaluated sleep with satisfactory agreement (76.5% night 1 and 81.6% night 3) that improved over the first three nights of hospitalization (p < 0.03). When the nurses' report did not agree with the actigraph, they tended to overestimate sleep. Patients tended to underestimate their total sleep time and total time awake after sleep onset. Time in bed and initial sleep latency were overestimated. There was great intersubject variability, making determination of agreement impossible. This data suggest that treatment teams on psychiatric units should in general consider nursing reports of sleep more accurate than patient self-report. However, since nursing staff and patients observe different aspects of sleep, both sources of data are important to inpatient treatment teams on clinical units.

Adult↗

PubMed1997

Comorbidity of dementia and psychiatric disorders in older persons.

To further investigate the relationship between psychiatric disorders and dementia in elderly patients, the authors drew a population-based, age-stratified random sample from residents of Rochester, Minnesota, age 65 and older. A trained paramedic completed a 90-minute screening interview, including the Symptom Checklist-90, Mini-Mental State Exam, and Auditory-Verbal Learning Test. Persons failing the screens were interviewed by a psychiatrist and a neurologist. DSM-III-R diagnoses were assigned for dementia and other psychiatric disorders. Of 201 participants, 37 were evaluated further by both neurologist and psychiatrist. One received a psychiatric diagnosis alone. Dementia alone was present in four people. Concurrent psychiatric diagnoses and dementia were found in 17 subjects. Much of the psychopathology found in older persons occurs in people with cognitive impairment. Current diagnostic nosology may not be able to capture the interrelatedness of psychiatric syndromes and cognitive impairment in elderly patients.

Aged↗

PubMed1997

The hepatoprotective and therapeutic effects of propolis ethanol extract on chronic alcohol-induced liver injuries.

Propolis designates a mixture of gums, resins and balms, of viscous consistency, which are gathered on certain parts (buds and bark, mainly) of vegetables (especially coniferous trees) by honeybees. They bring this back to the hive, where it is modified and mixed with other substances (essentially their own wax and salivary secretions). In this study, the hepatoprotective and therapeutic effects of propolis ethanol extract on chronic alcohol-induced liver injuries were investigated in rats. 3.125 ml of 99.5% alcohol was added to animal's daily diet for four weeks to induce chronic alcohol liver injuries. After sacrifice, serum transaminases (GOT, GPT), triacylglyceride and hepatic triacylglyceride (HTG) concentration were assayed to observe liver injuries induced by chronic alcohol abuse. In addition, the phenomenon of alcohol induced fatty liver were also observed by histopathological changes. Different doses of propolis ethanol extract were p.o. administered three times per day for three days, after four weeks' alcohol administration. It was found that 10 mg/kg of propolis ethanol extract significantly decreased the elevations of serum GOT, GPT, TG and HTG. In histopathological examination, 30 mg/kg of propolis ethanol extract also remarkably decreased the hepatocellular fatty degeneration, apparent as vacuolization, induced by chronic alcohol abuse.

Alanine Transaminase↗

PubMed1997

PDP1, a novel Drosophila PAR domain bZIP transcription factor expressed in developing mesoderm, endoderm and ectoderm, is a transcriptional regulator of somatic muscle genes.

In vertebrates, transcriptional control of skeletal muscle genes during differentiation is regulated by enhancers that direct the combinatorial binding and/or interaction of MEF2 and the bHLH MyoD family of myogenic factors. We have shown that Drosophila MEF2 plays a role similar to its vertebrate counterpart in the regulation of the Tropomyosin I gene in the development of Drosophila somatic muscles, however, unlike vertebrates, Drosophila MEF2 interacts with a muscle activator region that does not have binding sites for myogenic bHLH-like factors or any other known Drosophila transcription factors. We describe here the isolation and characterization of a component of the muscle activator region that we have named PDP1 (PAR domain protein 1). PDP1 is a novel transcription factor that is highly homologous to the PAR subfamily of mammalian bZIP transcription factors HLF, DBP and VBP/TEF. This is the first member of the PAR subfamily of bZIP transcription factors to be identified in Drosophila. We show that PDP1 is involved in regulating expression of the Tropomyosin I gene in somatic body-wall and pharyngeal muscles by binding to DNA sequences within the muscle activator that are required for activator function. Mutations that eliminate PDP1 binding eliminate muscle activator function and severely reduce expression of a muscle activator plus MEF2 mini-enhancer. These and previous results suggest that PDP1 may function as part of a larger protein/DNA complex that interacts with MEF2 to regulate transcription of Drosophila muscle genes. Furthermore, in addition to being expressed in the mesoderm that gives rise to the somatic muscles, PDP1 is also expressed in the mesodermal fat body, the developing midgut endoderm, the hindgut and Malpighian tubules, and the epidermis and central nervous system, suggesting that PDP1 is also involved in the terminal differentiation of these tissues.

Amino Acid Sequence↗

PubMed1997

Tropicamide eyedrops cannot be used for reliable diagnosis of Alzheimer's disease.

OBJECTIVE: To evaluate the mydriatic effect of tropicamide eyedrops as a diagnostic test for Alzheimer's disease. MATERIAL AND METHODS: In a double-blind, placebo-controlled study, we assessed pupillary responses in 22 normal control subjects, 23 patients with probable Alzheimer's disease, 4 patients with isolated memory difficulty, and 6 patients with non-Alzheimer's dementia. Three separate studies were performed, the second and third on a subset of the original group. With use of infrared binocular pupillography, after 5 minutes of dark adaptation, we averaged pupil size during a 1-minute interval for baseline determinations. We then instilled 0.01% tropicamide into one eye. In the first two studies, we averaged pupil size for a 1-minute period at 5-minute intervals for 30 minutes, followed by a pupil light reflex test. In the third study, we measured pupil size every 5 minutes for 45 minutes and omitted the light reflex test. RESULTS: No significant difference was noted in pupil dilatation between normal subjects and patients with Alzheimer's disease and between patients with non-Alzheimer's dementias and the Alzheimer's disease group in all three studies. Furthermore, on reperformance of the test in the same patients, more than 50% changed from a group above or below 13% pupil dilatation (a cutoff reported to distinguish Alzheimer's disease from normal control subjects) to the opposite group. CONCLUSION: Results of this study indicate that pupil measurement after instillation of tropicamide cannot be used as a reliable diagnostic test for Alzheimer's disease. Moreover, test-retest reliability with use of dilute tropicamide eyedrops is questionable.

Aged↗

PubMed1997

Metacercariae in fishes of Sun Moon lake which is an endemic area for Clonorchis sinensis in Taiwan.

The Sun Moon lake in Central Taiwan is a known endemic area for clonorchiasis. Of the 45 fresh water fish, Hemiculter leucisculus, from the lake that were examined by artificial gastric juice digestion in October 1995, all were found to harbor metacercariae in their muscle. The number of metacercariae isolated from each fish ranged from 2 to 2,185, with an average of 254. A total of 11,443 metacercariae was collected from the 45 fish. Of the 4,223 metacercaria that were examined under light microscope, 4,064 (96.23%) were found to belong to Haplorchis taichui, 90(2.13%) to H. pumilio, 2(0.05%) to C. sinensis and 67 (1.59%) to unknown species due to the metacercariae being not yet developed or immature. The 2 C. sinensis metacercariae were obtained from 2 out of 45 fish examined. Our results contrast with reports of a decade ago which stated that all the fish of the Sun Moon lake examined were positive for C. sinensis. Possible reasons for the decrease of C. sinensis metacercariae are the disappearance of pig farms around the lake, increased awareness of the trematode by the lakeside inhabitants and probably the exclusive use of mammals as its definitive host by C. sinensis. In contrast, besides mammals, Haplorchis spp also use birds as their definitive hosts.

Animals↗

PubMed1997

A proposal for a transfer standard for validating pulse oximeter sensors.

One method for validating a biosensor is through comparative assessment of the test sensor with a control sensor when both sensors are presented with the same inputs. In the case of adult pulse oximeter (SpO2) sensors, both sensors should ideally be placed on the same digit of the subject. However, at present, one SpO2 sensor interferes with another so that the two sensors are applied to two different digits, which may not be identical in SpO2 level. This article proposes a ring-shaped SpO2 sensor transfer standard that can be used on the same digit as the test sensor, based on the idea of timing, SpO2 is a slowly varying signal, while the two sensors can be gated to measure the same digit's SpO2 value very quickly. Hardware and software requirements for the transfer standard, and a statistical method for analyzing the data will be discussed. A method for the direct comparison of two SpO2 sensors using a "switch over" trial design will also be presented.

Adult↗