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Biomedical subjects

D Lin

Publications and source records attributed to D Lin.

At least 127 records · Page 7Linked to original sources
PubMed1996

Hypertension and outcomes research. From clinical trials to clinical epidemiology.

Outcomes research seeks to identify effective evidence-based methods of providing the best medical care. While randomized clinical trials (RCT) usually provide the clearest answers, they are often not done or not practicable. More than a decade after the introduction of calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors, clinical trial data about their effect on major disease endpoints in patients with hypertension are still not available. The primary alternatives are the use of randomized trials that include surrogate endpoints, such as level of blood pressure or extent of carotid atherosclerosis, and the use of observational studies that include major disease endpoints. Both approaches, their strengths and limitations, are discussed in detail. The possibility of residual confounding limits the strength of inferences that can be drawn from observational studies. Similarly, the possibility of important drug effects, other than those involving the surrogate endpoint, limits the inferences that can be drawn from randomized trials that rely solely on surrogate outcomes as guides to therapy. In the absence of evidence from large clinical trials that include major disease endpoints, treatment decisions and guidelines need to synthesize the best available information from a variety of sources. Consistency of findings across various study designs, outcomes, and populations is critical to the practice of evidence-based medicine and the effort to maximize the health benefits of antihypertensive therapies.

Clinical Trials as Topic↗
PubMed1996

Neonatal exposure to cocaine enhances the reward-potentiating properties of the drug in young adult animals.

Either cocaine (20 mg/kg) or saline vehicle was administered to rat pups once daily on postnatal days 1-8. The enhancement of brain stimulation reward (BSR) by acute administration of cocaine (2.5, 5, and 10 mg/kg i.p.) was assessed in adult offspring (70-90 days of age) using a rate-frequency curve-shift paradigm. Acute administration of cocaine produced orderly dose-related shifts of the rate-frequency function toward lower frequencies in all groups indicating a reward-enhancing effect of the drug on BSR. However, offspring neonatally exposed to cocaine displayed a greater drug-induced potentiation of BSR. Of particular note, the small but significant enhancement of the reward-potentiating properties of cocaine was more pronounced in female offspring neonatally exposed to the drug. These findings indicate that the rewarding properties of cocaine were altered by neonatal exposure to the drug in a sexually dimorphic fashion.

Age Factors↗
PubMed1996

Stimulation of cell elongation in teleost rod photoreceptors by distinct protein kinase inhibitors.

The rod photoreceptors of teleost retinas elongate in the light. To characterize the role of protein kinases in elongation, pharmacological studies were carried out with rod fragments consisting of the motile inner segment and photosensory outer segment (RIS-ROS). Isolated RIS-ROS were cultured in the presence of membrane-permeant inhibitors that exhibit selective activity toward specific serine/threonine protein kinases. We report that three distinct classes of protein kinase inhibitors stimulated elongation in darkness: (1) cyclic-AMP-dependent protein kinase (PKA)-selective inhibitors (H-89 and KT5720), (2) a protein kinase C (PKC)-selective inhibitor (GF 109203X) that affects most PKC isoforms, and (3) a kinase inhibitor (H-85) that does not affect PKC and PKA in vitro. Other kinase inhibitors tested neither stimulated elongation in darkness nor inhibited light-induced elongation; these include the myosin light chain kinase inhibitors ML-7 and ML-9, the calcium-calmodulin kinase II inhibitor KN-62, and inhibitors or activators of diacylglycerol-dependent PKCs (sphingosine, calphostin C, chelerythrine, and phorbol esters). The myosin light chain kinase inhibitors as well as the PKA and PKC inhibitors H-89 and GF 109203X all enhanced light-induced elongation. These observations suggest that light-induced RIS-ROS elongation is inhibited by both PKA and an unidentified kinase or kinases, possibly a diacylglycerol-independent form of PKC.

Animals↗
PubMed1996

Ultrasonic assessment of human and bovine trabecular bone: a comparison study.

A comparison study is reported on the ultrasonic assessment of human trabecular and bovine trabecular bone samples. Both ultrasonic velocity and ultrasonic attenuation were evaluated through a transmission insertion technique and correlated with bone mineral density as determined with single photon absorptiometry. For a 1-MHz ultrasonic transducer pair and the human cancellous bone samples the correlations were 0.91 and 0.89 between density and velocity and attenuation, respectively. For a 500-kHz ultrasonic transducer pair the correlations were 0.89 and 0.81 between density and velocity and attenuation, respectively. For the bovine bone samples, the correlations were 0.90 and -0.31 for the velocity and attenuation, respectively, for the 1 MHz transducer pair. For the 500-kHz transducers, the correlations were 0.85 and -0.17 for the velocity and attenuation, respectively. By combining both velocity and attenuation in a multivariate regression, an improvement was achieved in the estimation of bone density in the human samples for both the 500-kHz and 1-MHz transducer pairs. No significant improvement was achieved in the multivariate regressions for the bovine bone samples. In conclusion, the results indicate that ultrasonic measurements are in general highly correlated with bone mineral density in trabecular bone samples. This correlation is more consistent and strong in relatively low density human samples compared with the higher density bovine samples.

Adult↗
PubMed1996

Development of techniques for the genetic manipulation of the gliding bacteria Lysobacter enzymogenes and Lysobacter brunescens.

Lysobacter enzymogenes and Lysobacter brunescens are Gram-negative gliding bacteria that belong to the gamma subgroup of the proteobacteria. As a first step toward a molecular analysis of Lysobacter gliding motility, we developed techniques to genetically manipulate these bacteria. Cosmid pSUP106 of the broad host range incompatibility group Q (Inc Q) was introduced into L. enzymogenes and L. brunescens by conjugation and electroporation. pSUP106 replicated stably in both organisms and conferred antibiotic resistance. We also identified several other plasmids (pKT210, pH1JI) that functioned in L. enzymogenes and a transposon (mini-Tn5Sp) that functioned in L. brunescens. The identification of these tools allows genetic analysis of Lysobacter gliding motility, exoenzyme production, and production of antibiotics and other secondary metabolites.

Anti-Bacterial Agents↗
PubMed1996

[Correction of the secondary deformity of reduction mammaplasty--the inframammary fold advancement].

The high position of the nipple-areola is one of the complications of reduction mammaplasty. The technique of lower thoracic advancement flap reestablishes a new inframammary fold. The edge of the advanced inferior flap is sutured to the chest wall and the rib cage. The advantages of the technique is that the scar is hidden in the depth of the inframammary fold and is usually fairly in-conspicuous. The technique gives an increasingly natural looking of the breast. The operation is appealingly easy and safe. Figures illustrate the effectiveness of this technique.

Adult↗
PubMed1996

[The diagnostic value of thoracoscopy in pleural mesothelioma].

OBJECTIVE: To analyse the diagnostic value of thoracoscopy in pleural mesothelioma. METHODS: The image features under thoracoscopy and the histology of 32 patients with pleural mesothelioma were reported. And the diagnostic rate of thoracoscopy was compared with those of chest X-ray, CT, effusion fluid cytology, tomography and the percutaneous needle pleural biopsy. RESULTS: The diagnostic rate of thoracoscopy in pleural mesothelioma was 100%, and the histologic subtypes were the benign fibrous (5 cases), epithelial (9 cases), fibrosarcoma (12 cases) and the mixed (6 cases). The positive rates of chest X-ray, tomography, pleurography, CT, effusion fluid cytology and the percutaneous needle pleural biopsy were 13%, 33%, 38%, 61%, 15% and 24% respectively. CONCLUSION: Thoracoscopy was found to be the best method for diagnosing pleural mesothelioma, by which all pleural lesions could be observed and biopsied directly.

Adolescent↗
PubMed1996

[Study of electrophysiological properties of large conductance K(+)-channels in outer hair cells from the guinea pig with patch-clamp technique].

The basic electrophysiological characteristics of large conductance K(+)-channels in the basolateral cell membrane of outer hair cells (OHC) from the guinea pig cochlea were studied with patch-clamp technique. Acutely isolated OHC preparations were obtained by enzymatic digestion and excised patches were made in cell-attached configuration to record single-channel currents led by patch-clamp micropipette and fed to patch-clamp amplifier. Data were sampled and analyzed on-line with a computer. The result showed that the typical properties of single channels of large conductance K(+)-channels were: 1. The channel was activated by depolarization of membrane and it showed a marked voltage-dependence. The channel had a unitary conductance of about 133 pS and the channel current reversed at about -30mV under asymmetrical K+ concentration gradient. 2. Tetraethylammonium (TEA, > 10 mmol/L), a potassium channel blocker, dose-dependently abolished the outward current. 3. The open probability (Po) and mean open time of this channel was markedly increased with elevation of cytoplasmic Ca2+ concentration. These results suggest that a population of voltage-dependent and Ca(2+)-activated K+ channel exists in the basolateral membrane of OHC of the guinea pig; it is characterized by a very high unitary conductance and high sensitivity to Ca2+ and is blocked by K+ channel blocker. This work provided valuable basic materials for further study on the regulation and drug influence of the type of single channels.

Animals↗
PubMed1995

Structure of the human steroidogenic acute regulatory protein (StAR) gene: StAR stimulates mitochondrial cholesterol 27-hydroxylase activity.

Steroidogenic acute regulatory protein (StAR) plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. We determined the organization of the StAR structural gene, mapped to 8p11.2. The gene spans 8 kb and consists of seven exons interrupted by six introns. The 1.3 kb of DNA upstream from the transcription start site directed expression of a luciferase reporter gene in mouse Y-1 adrenal cortical tumor cells but not in BeWo choriocarcinoma cells. Reporter gene expression in the Y-1 cells was increased more than 2-fold by 8-Br-cAMP, indicating that the 1.3 kb DNA fragment contains sequences that confer tissue-specific expression and cAMP regulation. The sequence of a related StAR pseudogene, mapped to chromosome 13, lacks introns and has an insertion, numerous substitutions, and deletions. Expression of StAR in COS-1 cells cotransfected with cholesterol 27-hydroxylase (P450c27) and adrenodoxin resulted in a 6-fold increase in formation of 3 beta-hydroxy-5-cholestenoic acid, demonstrating that StAR's actions are not specific to steroidogenesis but extend to other mitochondrial cholesterol-metabolizing enzymes.

Animals↗
PubMed1995

Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13.

Steroidogenic acute regulatory protein (StAR) appears to mediate the rapid increase in pregnenolone synthesis stimulated by tropic hormones. cDNAs encoding StAR were isolated from a human adrenal cortex library. Human StAR, coexpressed in COS-1 cells with cytochrome P450scc and adrenodoxin, increased pregnenolone synthesis > 4-fold. A major StAR transcript of 1.6 kb and less abundant transcripts of 4.4 and 7.5 kb were detected in ovary and testis. Kidney had a lower amount of the 1.6-kb message. StAR mRNA was not detected in other tissues including placenta. Treatment of granulosa cells with 8-bromo-adenosine 3',5'-cyclic monophosphate for 24 hr increased StAR mRNA 3-fold or more. The structural gene encoding StAR was mapped using somatic cell hybrid mapping panels to chromosome 8p. Fluorescence in situ hybridization placed the StAR locus in the region 8p11.2. A StAR pseudogene was mapped to chromosome 13. We conclude that StAR expression is restricted to tissues that carry out mitochondrial sterol oxidations subject to acute regulation by cAMP and that StAR mRNA levels are regulated by cAMP.

Animals↗
PubMed1995

The expression of prostatic acid phosphatase is transcriptionally regulated in human prostate carcinoma cells.

The expression of prostatic acid phosphatase (PAcP) in three human prostate carcinoma cell lines including LNCaP, DU 145 and PC-3, was studied to explore its potential role as a marker in the progression of prostate cancer. Although Southern blot analysis suggested the presence of PAcP gene in all three prostate carcinoma cell lines, the Northern blot analysis and the reverse transcriptase-polymerase chain reaction (RT-PCR) assay showed that PAcP mRNA can be detected only in LNCaP cells. As one of the major differences between LNCaP cells and PC-3 as well as DU 145 cells is the androgen-sensitivity of LNCaP cells, we then focused on the influence of PAcP expression by the presence of androgen receptor (AR) in human AR cDNA-transfected PC-3 cells and high passages of LNCaP cells. The results demonstrated that the transfection of human AR cDNA into PC-3 cells did not have any detectable effect on the expression of PAcP. Further, in LNCaP cells, while the level of PAcP mRNA diminished upon passage, the AR mRNA level remained approximately the same. Together, these data suggested that the differential expression of PAcP in different prostate carcinoma cells including high passages of LNCaP cells may occur at the transcriptional level and may have little linkage to the expression of AR.

Acid Phosphatase↗
PubMed1995

Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis.

Congenital lipoid adrenal hyperplasia is an autosomal recessive disorder that is characterized by impaired synthesis of all adrenal and gonadal steroid hormones. In three unrelated individuals with this disorder, steroidogenic acute regulatory protein, which enhances the mitochondrial conversion of cholesterol into pregnenolone, was mutated and nonfunctional, providing genetic evidence that this protein is indispensable normal adrenal and gonadal steroidogenesis.

Adrenal Glands↗
PubMed1995

Developmental analysis of the Hba(th-J) mouse mutation: effects on mouse peri-implantation development and identification of two candidate genes.

The Hba(th-J) mouse mutation is a deletion on chromosome 11 that spans the alpha-globin complex and causes alpha-thalassemia in heterozygous animals and in utero death of embryos homozygous for the deletion. We hypothesised that one or more genes closely linked to the Hba locus are also deleted in these mutant mice and that deletion of these additional genes is responsible for the embryo lethality. We have analysed the developmental profile of mutant embryos using a PCR assay to distinguish homozygous embryos from wild-type and heterozygous embryos. No homozygous embryos are detectable on Day 6.5 of gestation and morphological analysis of embryos on Day 5.5 shows that both the embryonic and extraembryonic ectoderm of the egg cylinder are reduced in size and contain degenerate cells. Preimplantation homozygous embryos are morphologically normal with the same proportion developing to the blastocyst stage as control embryos. However, the cell number of homozygous embryos on Day 4.5 is significantly reduced due predominantly to a decrease in the cell number of the trophectoderm and not the inner cell mass. When homozygous blastocysts are plated in vitro, outgrowth of giant trophectoderm cells appears similar to that of wild-type embryos but outgrowth of the inner cell mass is affected. Cells from the inner cell mass of homozygous embryos appear to undergo necrosis and dissociate from the trophectoderm outgrowth after 3 to 4 days in culture. These studies demonstrate that the development of both the inner cell mass and the trophectoderm of embryos homozygous for the Hbath-J deletion is affected by the mutation. We have used quantitative Southern blotting to show that 3-methyladenine glycosylase (mpg) and dist1, two genes closely linked to the Hba locus on chromosome 11, are also deleted in this mutation. Reverse transcriptase-polymerase chain reaction analyses demonstrate that mpg and dist1 are normally expressed by preimplantation and early postimplantation embryos, whereas alpha-globin transcripts from the Hba locus are not detected until Day 7.5 of gestation. These studies demonstrate that deletion of the mpg or dist1 genes is likely to be responsible for the homozygote embryo lethality and the potential roles of these gene products in early embryogenesis are discussed.

Animals↗
PubMed1995

Use of the guinea pig flank flap in skin flap research.

A variety of flaps in laboratory animals have been designed that propose to parallel the behavior of human skin under different experimental conditions. In the search for a readily available and affordable island skin flap model that combines reliable anatomy with a pedicle of substantial size, we have designed in the guinea pig a cutaneous flap based on the superficial circumflex iliac artery and vein. In 22 adult female Hartley guinea pigs, an 8 x 4 cm flank flap based on the superficial circumflex iliac pedicle was raised, and its characteristics were evaluated for applications to skin flap research. Dermofluorometric studies were performed that confirm the vascularity of this flap, and 100% survival of the flap was seen 5 days after surgery in all animals. Of particular benefit was the demonstration that both afferent and efferent blood samples can be taken from the pedicle directly, which allows for the direct quantification of plasma markers after physiologic insults to the skin flap, such as burn or ischemia. This anatomically reliable and easily dissected flap lends itself well to preliminary skin flap research and may contribute to standardization of a model for further studies examining the behavior of skin microcirculation under adverse physiologic conditions.

Animals↗
PubMed1995

Evidence for D4 receptor regulation of retinomotor movement in isolated teleost cone inner-outer segments.

In the retinas of teleost fish, cone photoreceptors change shape in response to light and circadian signals. They elongate in the dark, contract in the light, and under conditions of constant darkness undergo appropriate movements at expected dusk and dawn. Dopamine induces cones to contract, thus mimicking the effect of light or expected dawn. To identify the receptor subtype responsible for mediating dopamine regulation of cone retinomotor movements, we have carried out pharmacological studies using isolated fragments of teleost cones consisting of cone inner segments-cone outer segments (CIS-COS). Isolated CIS-COS retain the ability to elongate in dark culture and contract when subsequently exposed to light or dopamine. We report that dark-induced elongation of CIS-COS was inhibited by dopamine and its agonists with an effectiveness ranking of dopamine = quinpirole > bromocriptine >>> SKF-38393. After 60 min of elongation in dark culture, CIS-COS myoids contracted when subsequently cultured in the dark with dopamine or quinpirole. Quinpirole-induced inhibition of elongation and quinpirole-induced contraction were completely blocked by clozapine at 1 microM or by sulpiride at 100 microM. These effectiveness profiles for dopamine agonists and antagonists suggest that dopamine regulation of cone retinomotor movement is mediated by a D4-like receptor.

Animals↗
PubMed1995

T-->A transversion 11 bp from a splice acceptor site in the human gene for steroidogenic acute regulatory protein causes congenital lipoid adrenal hyperplasia.

Congenial lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH. Affected individuals can make no adrenal or gonadal steroids. All affected individuals are phenotypic females irrespective of gonadal sex, and frequently die in infancy if mineralocorticoid and glucocorticoid replacements are not instituted. Recent data implicate the steroidogenic acute regulatory (StAR) protein in this disorder. We now describe a 46,XY patient of Vietnamese ancestry with lipoid CAH who had a somewhat milder form of the disease. Diagnosis was at 10 weeks of age, and low levels of plasma progesterone, corticosterone, 180H-corticosterone and androstenedione were detectable. Testicular RNA for StAR was reverse transcribed, amplified, cloned and sequenced, revealing a 185 bp deletion corresponding to all of exon 5. The corresponding mRNA did not encode active protein in transfected cells. Cloned genomic DNA from the patient revealed only a T-->A transversion in intron 4,11 bp from the splice acceptor site of exon 5. This transversion destroys an NcoI site; digestion of PCR-amplified genomic DNA from the patient and both parents confirmed that the patient was homozygous and the parents were heterozygous. Expression vectors for StAR minigenes were constructed containing all StAR exons plus introns 4, 5 and 6 either with or without the T-->A mutation in intron 4. RNase protection assays showed that expression of the vector with normal intron 4 yielded correctly spliced StAR mRNA in transfected COS-1 cells, while most, but not all StAR mRNA from the vector with the T-->A transversion in intron 4 was abnormally spliced. RNase protection of the patient's testicular RNA confirmed that most, but not all StAR mRNA was similarly spliced abnormally. Splicing errors appear to be a rare cause of genetic diseases, but subtle intronic mutations may be missed when genomic DNA is the only material available for study. The low level of normal StAR mRNA produced may account for the later clinical presentation and low levels of steroid hormones detected in this patient.

Adrenal Hyperplasia, Congenital↗