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Biomedical subjects

S Li

Publications and source records attributed to S Li.

At least 1,207 records · Page 67Linked to original sources

Clinicohistopathological findings of gelatinous droplike corneal dystrophy among Asians.

We describe the findings in nine Asian-Indian patients with gelatinous droplike corneal dystrophy (GDCD). Most patients showed initial signs of bilateral decreased vision and photophobia at an early age. The siblings were affected in four cases, and parental consanguinity was recorded in seven cases. We classified the disease into three forms based on clinicopathologic findings. Clinically, the mild form of the disease was evidence by central subepithelial, whitish-yellow, nodular lesions that corresponded to the subepithelial nodular deposits seen histologically. In the moderate form, the lesions coalesced, forming central, diffuse subepithelial lesions with superficial vascularization. On histology, the amyloid deposits assumed a sheetlike distribution in the subepithelial regions and in the superficial stroma. Aggregates of chronic inflammatory cells and stromal neovascularization were seen in the adjacent stroma. The severe form presented as diffuse, whitish opacification of the cornea with extensive neovascularization and scarring. Histologically this form was characterized by a visible plaque of vascularized scar tissue that partly replaced the stroma and enveloped the amyloid deposits. Frequent, early recurrence of the disease was noted in the grafts. This study provides a detailed clinicopathologic description of GDCD from the Indian subcontinent. We also discuss previously unreported findings from the most advanced stage of the disease.

Adolescent↗

Mesenchymal regulation of differentiation of intestinal epithelial cells.

Intestinal epithelial differentiation requires the presence of mesenchyme, but the exact nature of this epithelial-mesenchymal interaction is unknown. The role of humoral and extracellular matrix factors in determining intestinal epithelial differentiation was examined by exposing a nontransformed, immature, rat small-intestinal cell line (IEC-6) to intestinal fibroblast-conditioned media or by growing the cells on matrix deposited by intestinal fibroblasts. Differentiation was assessed morphologically and by induction of the disaccharidase sucrase, which is a marker of intestinal epithelial maturation. When exposed to fetal intestinal fibroblast-conditioned medium or grown on extracellular matrix prepared from fetal intestinal fibroblasts, IEC-6 cells showed a significant increase in sucrase activity. The addition of cortisol to IEC-6 cells cultured on intestinal matrix also led to increased sucrase expression, as measured by enzyme activity and protein and messenger RNA levels. Ultrastructurally, cells cultured on intestinal fibroblast matrix in the presence of cortisol displayed a more differentiated phenotype. In contrast, there was no induction of sucrase activity in cells exposed to lung-conditioned media or grown on lung fibroblast matrix. These studies suggest that both humoral and matrix factors from intestinal mesenchyme are involved in intestinal epithelial differentiation and that these factors appear to be organ specific.

Animals↗

Injury to vascular endothelial cells and the change of plasma endothelin level in dogs with gunshot wounds.

The purpose of this study was to evaluate the relationship between injury to endothelial cells and the plasma endothelin level after gunshot wounds. Forty dogs were divided into four groups. The dogs in group 1 served as a control. The dogs in groups 2,3, and 4, respectively, were shot in both hind legs, in the hypogastric part of the abdomen, or in the right chest by military bullets (5.56 mm or 7.62 mm). After wounding, blood samples were taken at different intervals and the number of circulating endothelial cells (CEC), an indicator of injury to vascular endothelial cells (VEC), and the level of plasma endothelin were measured. Results showed that the CEC number increased in all groups immediately after wounding and showed a peak value at 10 minutes and at 6 hours. The change in plasma endothelin level paralleled that of the change of CEC number, and a linear relationship was found between them. These results suggest that, in gunshot wounds, extensive injury to VEC may be the result of the temporary cavity and shock waves produced by high velocity missiles striking the body and causing secretions of endothelin. The mechanism of injury to VEC after a gunshot wound in discussed in this paper.

Animals↗

Role of nitric oxide in sepsis-induced hyporeactivity in isolated rat lungs.

The aim of the present study was to test the hypothesis that pulmonary microvascular reactivity is depressed in sepsis and that inducible nitric oxide synthase (iNOS) contributes to the vascular hyporeactivity. Rats were made septic by cecal ligation and puncture. After 16 h, pulmonary vascular reactivity was evaluated by measurement of perfusion pressures while the vasculature was challenged with angiotensin II and KCl. The results showed that vascular reactivity was significantly depressed in lungs from septic rats in comparison to sham-operated controls. Pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) restored the depressed vasoreactivity while the nitric oxide (NO) synthase substrate L-arginine (1 mM) reversed the contraction-restoring effect of L-NAME. NO production in lungs from septic rats increased about 4-fold in comparison to sham-operated controls. iNOS protein was expressed in lung tissues, mainly the resistance vessels, from septic rats but not from sham-operated controls. Reverse transcription and polymerase chain reaction also showed a strong induction of iNOS mRNA in lung tissues from septic rats. These results suggest that increased iNOS expression and NO production may contribute to depressed pulmonary vascular reactivity in sepsis.

Animals↗

Alkaline unfolding and salt-induced folding of yeast alcohol dehydrogenase under high pH conditions.

The conformational changes of yeast alcohol dehydrogenase during unfolding at alkaline pH have been followed by fluorescence emission and circular dichroism spectra. A result of comparison of inactivation and conformational changes shows that much lower values of alkaline pH are required to bring about inactivation than significant conformational change of the enzyme molecule. At pH 9.5, although the enzyme has been completely inactivated, no marked conformational changes can be observed. Even at pH 12, the apparently fully unfolded enzyme retains some ordered secondary structure. After removal of Zn2+ from the enzyme molecule, the conformational stability decreased. At pH 12 by adding the salt, the relatively unfolded state of denatured enzyme changes into a compact conformational state by hydrophobic collapsing. Folded states induced by salt bound ANS strongly, indicating the existence of increased hydrophobic surface. More extensive studies showed that although apo-YADH and holo-YADH exhibited similar behavior, the folding cooperative ability of apo-enzyme was lower than that of holo-enzyme. The above results suggest that the zinc ion plays an important role in helping the folding of YADH and in stabilizing its native conformation.

Alcohol Dehydrogenase↗

A new source localization algorithm with no requirement of one-to-one source correspondence between biplane radiographs.

Conventional source localization algorithms require a one-to-one source correspondence between films. This requirement makes source localization cumbersome and error prone because multiple sources must be carefully digitized and some sources can be obscured or missed. A new source localization algorithm is described in this paper. The algorithm fits a ribbon or needle image on film to a linear-quadratic equation, then analytically determines the 3-D ribbon locus by its image on the other projection, and finally localizes the sources in the ribbon by tracing along the ribbon image. Only three points per ribbon per film are required, and corresponding points need not be identified on the other film. Phantom experiments and tests on clinical cases demonstrate that the source localization algorithm can increase the efficiency by a factor of up to 5, improve accuracy to about 1 mm, and reconstruct obscured or shifted sources without decreased accuracy and efficiency. The simplicity and minimal entry of data make this technique desirable for clinical use.

Algorithms↗

Development of an oligonucleotide probe for Aureobasidium pullulans based on the small-subunit rRNA gene.

Aureobasidium pullulans, a cosmopolitan yeast-like fungus, colonizes leaf surfaces and has potential as a biocontrol agent of pathogens. To assess the feasibility of rRNA as a target for A. pullulans-specific oligonucleotide probes, we compared the nucleotide sequences of the small-subunit rRNA (18S) genes of 12 geographically diverse A. pullulans strains. Extreme sequence conservation was observed. The consensus A. pullulans sequence was compared with other fungal sequences to identify potential probes. A 21-mer probe which hybridized to the 12 A. pullulans strains but not to 98 other fungi, including 82 isolates from the phylloplane, was identified. A 17-mer highly specific for Cladosporium herbarum was also identified. These probes have potential in monitoring and quantifying fungi in leaf surface and other microbial communities.

Base Sequence↗

Twin studies demonstrate a host cell genetic effect on productive human immunodeficiency virus infection of human monocytes and macrophages in vitro.

Biological and genetic variability is a prominent feature of human immunodeficiency virus (HIV) strains, especially in tropism, syncytium formation, and replicative capacity. To determine whether there were variable host cell effects on HIV replication in monocytes, three different strains of low-passage-number monocytotropic blood isolates of HIV and the laboratory-adapted strain Ba-L were inoculated into panels of adherent monocytes drawn from 44 different donors, and peak extracellular HIV p24 antigen titers were compared. The clinical HIV strains showed patterns of either moderate or low-level replication in most donor monocytes (20 to 4,000 pg/ml). However, within this range there was marked variation in peak titers in most donors. HIV type 1 Ba-L replicated in all donor monocytes to much higher levels with less variability (30 to 40 ng/ml). Furthermore, replication of 21 clinical blood-derived strains of HIV in blood monocytes and monocyte-derived macrophages (MDM) from pairs of identical twins and age-matched unrelated donors (URD) of the same sex were compared. In all of the seven pairs of identical twins, the kinetics of replication (measured by extracellular HIV p24 antigen) of panels of four clinical HIV type 1 isolates in monocytes were similar within pairs. However, marked and significant differences in kinetics of HIV production occurred within 10 of the 12 unrelated donor pairs (P = 0.0007). The remaining two URD pairs showed similar kinetic patterns, but only one pair had the same HLA-DR genotype. Similar results were observed with monocytes/MDMs obtained from a second bleed of the same donor. Hence, discordant patterns of HIV replication kinetics between URD monocyte pairs contrasted with concordant patterns in identical twin monocytes. These data strongly suggest a host cell genetic effect on productive viral replication in monocytes and MDMs. So far, no consistent genetic linkage of HIV replication pattern with HLA-DR genotype has been observed.

Adult↗

The Ras-JNK pathway is involved in shear-induced gene expression.

Hemodynamic forces play a key role in inducing atherosclerosis-implicated gene expression in vascular endothelial cells. To elucidate the signal transduction pathway leading to such gene expression, we studied the effects of fluid shearing on the activities of upstream signaling molecules. Fluid shearing (shear stress, 12 dynes/cm2 [1 dyne = 10(-5)N]) induced a transient and rapid activation of p21ras and preferentially activated c-Jun NH2 terminal kinases (JNK1 and JNK2) over extracellular signal-regulated kinases (ERK-1 and ERK-2). Cotransfection of RasN17, a dominant negative mutant of Ha-Ras, attenuated the shear-activated JNK and luciferase reporters driven by 12-O-tetradecanoylphorbol-13-acetate-responsive elements. JNK(K-R) and MEKK(K-M), the respective catalytically inactive mutants of JNK1 and MEKK, also partially inhibited the shear-induced luciferase reporters. In contrast, Raf301, ERK(K71R), and ERK(K52R), the dominant negative mutants of Raf-1, ERK-1, and ERK-2, respectively, had little effect on the activities of these reporters. The activation of JNK was also correlated with increased c-Jun transcriptional activity, which was attenuated by a negative mutant of Son of sevenless. Thus, mechanical stimulation exerted by fluid shearing activates primarily the Ras-MEKK-JNK pathway in inducing endothelial gene expression.

Animals↗

The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases.

We previously described IQGAP1 as a human protein related to a putative Ras GTPase-activating protein (RasGAP) from the fission yeast Schizosaccharomyces pombe. Here we report the identification of a liver-specific human protein that is 62% identical to IQGAP1. Like IQGAP1, the novel IQGAP2 protein harbors an N-terminal calponin homology motif which functions as an F-actin binding domain in members of the spectrin, filamin, and fimbrin families. Both IQGAPs also harbor several copies of a novel 50- to 55-amino-acid repeat, a single WW domain, and four IQ motifs and have 25% sequence identity with almost the entire S. pombe sar1 RasGAP homolog. As predicted by the presence of IQ motifs, IQGAP2 binds calmodulin. However, neither full-length nor truncated IQGAP2 stimulated the GTPase activity of Ras or its close relatives. Instead, IQGAP2 binds Cdc42 and Racl but not RhoA. This interaction involves the C-terminal half of IQGAP2 and appears to be independent of the nucleotide binding status of the GTPases. Although IQGAP2 shows no GAP activity towards Cdc42 and Rac1, the protein did inhibit both the intrinsic and RhoGAP-stimulated GTP hydrolysis rates of Cdc42 and Rac1, suggesting an alternative mechanism via which IQGAPs might modulate signaling by these GTPases. Since IQGAPs harbor a potential actin binding domain, they could play roles in the Cdc42 and Rac1 controlled generation of specific actin structures.

Actins↗

Fluid shear stress induces the phosphorylation of small heat shock proteins in vascular endothelial cells.

The small molecular mass heat shock protein of 27 kDa (HSP27) has been shown to influence actin filament dynamics and endothelial cell behavior in ways similar to those observed during laminar flow. We have employed human umbilical vein endothelial cells to determine whether fluid shear stress affects HSP27 expression or phosphorylation. After a shear stress of 16 dyn/cm2, HSP27 became more highly phosphorylated, with maximum increase in phosphorylation levels (3-fold) attained by 30 min and sustained for at least 20 h. HSP27 antigen levels did not change; however, HSP27 mRNA levels decreased by 20% after 16 h. In bovine aortic endothelial cells stably transfected with the wild-type human HSP27 gene, shear stress induced the phosphorylation of both the exogenous human HSP27 and the endogenous bovine HSP25. The product of a transfected mutant HSP27 gene in which the putative phosphorylation sites Ser-15, Ser-78, and Ser-82 had been replaced with Gly was not phosphorylated. Thus the modulation of HSP27 and its activity by shear stress is mediated through a posttranslational mechanism and differs from the shear stress induction of immediate early genes at the level of transcription.

Animals↗

Transforming growth factor-beta modulation of the alpha 1(IV) collagen gene in murine proximal tubular cells.

We have examined the expression of the alpha 1(IV) collagen gene in murine proximal tubular cells (MCT) to better understand how it is regulated in parenchymal cells. Transcriptional activity was examined using luciferase reporters driven by the alpha 1(IV) promoter and varying lengths of 5'-flanking sequences. The minimal bidirectional promoter showed low intrinsic activity in MCT cells, but addition of upstream sequences increased luciferase expression. Maximal activity resided within the first 1,200 bp upstream. A minigene construct was generated by placing a portion of the alpha 1(IV) first intron downstream from the promoter region. The intronic sequences significantly decreased activity of the promoter in MCT cells and 3T3 fibroblasts but greatly enhanced expression in murine parietal yolk sac (PYS) endodermal cells. Addition of transforming growth factor-beta (TGF-beta) to MCT cultures elevated the levels of secreted type IV collagen. Treatment of either transiently or stably transfected MCT cells with TGF-beta produced an increase in the levels of expression of all of the reporters tested. These data support the hypothesis that cell-specific regulation of alpha 1(IV) collagen is dependent upon downstream sequences, which act to decrease the expression of type IV collagen in tubular epithelium. The activity of the alpha 1(IV) collagen gene in proximal tubular cells is increased by TGF-beta, which acts on the domain(s) embedded within the intergenic bidirectional promoter.

3T3 Cells↗

Further studies on the mechanism of action of the endogenous benzodiazepine receptor ligand octadecaneuropeptide on gonadotropin-releasing hormone gene expression in the rat brain.

We have recently reported that the intracerebroventricular injection of the endogenous benzodiazepine (BZD) receptor ligand octadecaneuropeptide (ODN) (30 micrograms/kg b.w.) could induce a decrease in gonadotropin-releasing hormone (GnRH) mRNA levels in the male rat brain. This inhibitory effect could be completely reversed by the concomitant administration of the GABAA antagonist picrotoxin. In order to further investigate the mechanism of action of ODN, we investigated the effects of intracerebroventricular injection of a smaller dose of ODN (3 micrograms/kg b.w.) and the influence of the GABAA receptor agonist muscimol and the antagonist to BZD receptors flumazenil on GnRH gene expression. Treatment with ODN induced a 40% decrease in mRNA levels, an effect which was potentiated by the concomitant administration of muscimol. The administration of flumazenil produced a small increase in GnRH mRNA while the inhibitory effect of ODN on GnRH mRNA levels was completely prevented by the administration of this BZD antagonist. Moreover, the intravenous administration of increasing doses of ODN also induced a marked decrease of 33, 32 and 38% for 75, 150 and 300 micrograms/kg b.w., an effect which was completely abolished by picrotoxin. These data clearly indicate that an endogenous neuropeptide can activate the GABAA BZD receptor complex to negatively modulate the activity of GnRH neurons. They also suggest that this peptide or other endogenous activators of the GABAA BZD receptors might exert a tonic inhibitory influence on GnRH gene expression.

Animals↗

Hydrolytic degradation of the coral/poly(DL-lactic acid) bioresorbable material.

A bioresorbable composite material composed of a high molecular weight poly(DL-lactic acid) and granules of natural coral (40/60 w/w) was made by blending in acetone with further evaporation of the solvent. The blend and the unfilled polymer matrix were compression moulded and machined to yield 12 x 12 mm plates of different thicknesses (1.4 mm for the blend vs 2.1 mm for the polymer). The resulting plates were allowed to age at 37 degrees C in a pH 7.4 isoosmolar phosphate buffer solution taken as a model of body fluids. Hydrolytic degradation of the blend was investigated comparatively with the unfilled polymer matrix. The fate of the specimens was monitored by weighing, enzymatic assay, size-exclusion chromatolography and differential scanning calorimetry. Data on water absorption, weight loss, release of L-lactic acid, molecular weight and morphology changes conclusively showed that the presence of coral dramatically modified the degradation characteristics of poly(DL-lactic acid). In particular, the faster internal degradation observed for the unfilled polymer matrix was not detected for the blend. This finding was assigned to the buffering effect of calcium carbonate which neutralized the carboxyl end groups of the degradation products and to the presence of coral/polymer interfaces which facilitated ion exchanges with the external solution, both contributing to eliminate autocatalysis.

Animals↗

Angiotensin-converting enzyme gene polymorphism in essential hypertensive patients in Japanese population.

Association between angiotensin-converting enzyme (ACE) gene polymorphism and essential hypertension in a Japanese population with the same socioeconomic background was investigated. Insertion-deletion (I/D) polymorphism of the ACE gene located on intron 16 was detected by polymerase chain reaction. Association between ACE gene polymorphism and family history of essential hypertension as well as the development of vascular damage in eye fundi were also investigated. Variation at ACE loci did not contribute to essential hypertension and the vascular damages in eye fundi. These results suggest that the ACE gene was not directly responsible for essential hypertension in this particular Japanese population with the same socioeconomic background.

Adult↗

Prolactin response to fenfluramine and suicide attempt lethality in major depression.

BACKGROUND: This study employed an alternative method for assessing serotonergic function to further evaluate our finding that cerebrospinal fluid (CSF) 5-hydroxyindole acetic acid (5-HIAA) in depressed suicide attempters with a lifetime history of higher lethality suicide attempts is significantly lower compared to depressed patients who have a history of low lethality suicide attempts. METHOD: We used dl-fenfluramine (60 mg) as a neuroendocrine probe to examine the serotonin system in 41 in-patients with a DSM-III-R major depressive episode, divided into two groups on the basis of a lifetime history of high or low lethality suicide attempts. Fenfluramine challenge test outcome was defined as the maximum prolactin response in the five hours following fenfluramine. RESULTS: Patients with a history of a higher lethality suicide attempt had a significantly lower prolactin response to fenfluramine, even when controlling for cortisol, age, sex, weight, comorbid cluster B personality disorder, pharmacokinetic and menstrual cycle effects. CONCLUSIONS: The data provide further support for the hypothesis that serotonin dysfunction is associated with more lethal suicide attempts, and suggests that higher lethality suicide attempters or failed suicides resemble completed suicides both behaviourally and biochemically.

Adult↗

The porous-coated anatomic total hip prosthesis: failure of the metal-backed acetabular component.

One hundred and ninety-nine total hip arthroplasties were performed, between 1983 and 1987, in 173 patients by three surgeons using the initial design of the porous-coated anatomic prosthesis. The acetabular component was a preassembled, metal-backed polyethylene device, with beads sintered to the metal backing to allow bone ingrowth and two pegs for initial fixation. Twenty-three acetabular components (12 percent) failed because of either migration or severe osteolysis. The radiographic appearance of osteolysis was positively associated with the duration that the implant had been in situ (p < 0.001). The prevalence of osteolysis was also significantly greater in acetabular components with an outer diameter of fifty-five millimeters or less (a polyethylene thickness of 8.5 millimeters or less) (p = 0.03). Thirteen hips were revised at a mean of 69.5 months (range, thirty-three to ninety-one months) after the index operation. Examination of the retrieved acetabular components revealed extensive polyethylene damage on the articular and back surfaces of the liners. Cracks in the polyethylene rim of the liner and deformation of the anti-rotation notch in the polyethylene rim were common findings. The density of the polyethylene was greater than expected, and more particles than anticipated had not fused with the surrounding polyethylene. The results of this study suggest that factors related to both the design and the material contributed to the failure of these porous-coated anatomic acetabular components.

Acetabulum↗

Effect of beta-glucanase supplementation to hulless barley- or wheat-soybean meal diets on the digestibilities of energy, protein, beta-glucans, and amino acids in young pigs.

Studies were carried out to determine the effect of beta-glucanase supplementation to hulless barley-soybean meal (HB+SBM) or wheat-soybean meal (W+SBM) diets on the digestibilities of GE, CP, beta-glucans, and amino acids. Twelve barrows, average BW 7.3 kg, were fitted with a simple T-cannula at the distal ileum, approximately 5 cm from the ileo-cecal sphincter. After a 7-d recuperation period, six pigs were allotted to each dietary treatment according to a two-period crossover design. Both diets were formulated to contain 20% CP without and with supplementation of .2% beta-glucanase. beta-glucanase refers to a mixture of enzymes with endo- and exo-beta-glucanase and beta-glucosidase activities. Chromic oxide was included as a digestibility marker. The pigs were fed three times daily at 0800, 1600, and 2400 and the daily allowance was offered at a rate of 5% of BW. Each experimental period lasted 9 d. Feces were collected for 48 h on d 6 and 7 and ileal digesta for a total of 24 h on d 8 and 9. beta-glucanase supplementation to the HB+SBM diet increased (P < .05 or P < .01) the ileal digestibilities of GE, CP, beta-glucans, and the majority of the amino acids and the fecal digestibilities of GE, CP, and all amino acids measured; the fecal digestibility of beta-glucans in the HB+SBM diet was not affected by beta-glucanase supplementation. There was no effect (P > .05) of beta-glucanase supplementation to the W+SBM diet on the ileal digestibilities of any criteria measured except for beta-glucans (P < .05). The supplementation of beta-glucanase to the W+SBM diet increased (P < .05) the fecal digestibility of energy but not (P > .05) the other criteria measured.

Amino Acids↗