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Biomedical subjects

L L Wang

Publications and source records attributed to L L Wang.

At least 19 recordsLinked to original sources

QSPRs for the prediction of photodegradation half-life of PCBs in n-hexane.

By partial least squares (PLS) regression analysis, a quantitative structure-property relationship (QSPR) model was developed for photodegradation half-life (t1/2) of polychlorinated biphenyls (PCBs) in n-hexane solution under UV irradiation. Quantum chemical descriptors computed by PM3 Hamiltonian were used as predictor variables. The cross-validated value for the optimal QSPR model was 0.589, indicating good predictive capability for log t1/2 values of PCBs in n-hexane. The QSPR results show that standard heat of formation (DeltaHf), total energy (TE), and molecular weight (Mw) have dominant effect on t1/2 values of PCBs in n-hexane. Increasing DeltaHf and TE values or decreasing Mw values of the PCBs leads to decrease of log t1/2 values. In addition, increasing the largest negative atomic charge on a carbon atom and dipole moment of the PCBs leads to decrease of log t1/2 values.

Environmental Pollutants↗

Successful umbilical cord blood stem cell transplantation in a patient with Rothmund-Thomson syndrome and combined immunodeficiency.

The ATP-dependent DNA helicase Q4 (RECQL4) belongs to a family of conserved RECQ helicases that are felt to be important in maintaining chromosomal integrity (Kitao et al., 1998, Genomics: 54 (3): 443-452). Deletions in the RECQL4 gene located on chromosome 8 region q24.3 have been associated with Rothmund-Thomson syndrome (RTS, OMIM 268400), a condition characterized by poikiloderma, sparse hair, small stature, skeletal abnormalities, cataracts and an increased risk of malignancy. We present a patient with a molecularly confirmed diagnosis of RTS with two unique genetic alterations in RECQL4 (IVS16-2A>T and IVS2+27_51del25), who at the age of 7 months nearly succumbed to Pneumocystis carinii pneumonia. Evaluation of his immune system demonstrated a T- B+ NK- phenotype with agammaglobulinemia consistent with combined immunodeficiency (CID). Studies to evaluate for known genetic causes of CID were not revealing. The patient received an umbilical cord blood (UCB) transplant with complete immune reconstitution. This report represents the first description of a CID phenotype and UCB transplantation in a patient with RTS.

Agammaglobulinemia↗

Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold syndrome caused by mutations in the RECQL4 gene.

Baller-Gerold syndrome (BGS) is a rare autosomal recessive condition with radial aplasia/hypoplasia and craniosynostosis (OMIM 218600). Of >20 cases reported so far, a few appear atypical and have been reassigned to other nosologic entities, including Fanconi anaemia, Roberts SC phocomelia, and Pfeiffer syndromes after demonstration of corresponding cytogenetic or molecular abnormalities. Clinical overlap between BGS, Rothmund-Thomson syndrome (RTS), and RAPADILINO syndrome is noticeable. Because patients with RAPADILINO syndrome and a subset of patients with RTS have RECQL4 mutations, we reassessed two previously reported BGS families and found causal mutations in RECQL4 in both. In the first family, four affected offspring had craniosynostosis and radial defect and one of them developed poikiloderma. In this family, compound heterozygosity for a R1021W missense mutation and a g.2886delT frameshift mutation of exon 9 was found. In the second family, the affected male had craniosynostosis, radial ray defect, poikiloderma, and short stature. He had a homozygous splice site mutation (IVS17-2A>C). In both families, the affected offspring had craniosynostosis, radial defects, and growth retardation, and two developed poikiloderma. Our results confirm that BGS in a subgroup of patients is due to RECQL4 mutations and could be integrated into a clinical spectrum that encompasses RTS and RAPADILINO syndrome.

Abnormalities, Multiple↗

Ablation of canine prostate using two-stage intraprostatic hot agarose solution and enzyme injection.

UNLABELLED: Enzyme ablation of the hyperplastic prostate may be an ideal method of management of BPH. However, the unsatisfactory ablation affects in vivo contrast with successful in vitro results limiting the enthusiasm for further research. In this study, we make efforts to solve the problems in the use of enzyme ablation of BPH in vivo and to measure satisfactory effect. MATERIAL AND METHODS: A total of 18 hybrid dogs between the ages of 7 and 11 y underwent this experiment. Eight dogs were divided into four groups according to the injection formula: enzyme solution, hot D-Hanks' plus enzyme solution, hot agarose plus enzyme solution, and hot agarose solution alone. After selecting the agarose plus enzyme solution group in the first month, the remainder 10 dogs were treated with this two-stage method. Intravenous or oral antibiotics were administered perioperatively. All operations were performed directly by way of laparotomy. The prostates were observed and harvested with surrounding tissue at 24 hrs, 7 days, 14 days, 1 month and 3-5 months after treatment. Gross and microscopic examinations were performed. RESULTS: Only agarose plus enzyme group shows obvious cavity formation with concomitant size reduction and softening of the prostate ablation effect in the four groups. At 24 h after injection, the prostates demonstrated cavity formation containing liquefied necrotic tissue. The liquefied tissue was absorbed in 7-14 days. At 1 month, the size of most prostates decreased with a corresponding decrease in the size of the cavities. The cavities nearly disappeared within 3-5 months, and the size of prostates decreased to between 1/2 and 1/4 of the pretreatment sizes. All prostates had intact urethral mucosa and capsule. No complications directly related to enzyme ablation were identified. In the control groups there were no significant cavities or decrease in prostate size. CONCLUSIONS: This two-stage thermal and enzyme ablative method can significantly ablate prostate tissue without identifiable complications, and would be possibly applied to treating human BPH in the future.

Administration, Oral↗

Effect of distraction rate and consolidation period on bone density following mandibular osteodistraction in rats.

The high cost of large animal protocols has limited the study of distraction osteogenesis (DO) in the craniofacial region. This study was designed to characterise a rat model for DO with regard to distraction rate and consolidation period. Unilateral mandibular distraction was performed on 129 male Sprague-Dawley rats using an osteotomy from the sigmoid notch to the inferior border of mandible. After a 3-day latency, 12 groups of 8-9 rats underwent distraction for 5 days at four different rates (0, 0.2, 0.4, 0.6mm per day), with three different post-osteotomy sacrifice times (10, 24, and 38 days) and four final predicted distraction lengths (0, 1, 2, and 3mm). Another four groups of rats (N=8 per group) were sacrificed 6 days post-osteotomy, resulting in distraction for 3 days with a predicted distraction length of 0, 0.6, 1.2, 1.8mm. Changes in mandibular morphology were measured from radiographs of disarticluated hemimandibles. The bone density of the regenerate and control sites was measured using microdensitometry calibrated with an epoxy stepwedge. Distraction linearly increased mandibular length, distraction gap width and the area of the distraction gap (P<0.00005). Mandibular length increased by 0.394 mm per distraction rate. Gap width and area increased by 0.67 and 5.8mm(2) per distraction rate, respectively. The increase in length represents only 39.4% of what was predicted, suggesting that compensatory alteration in condylar or mandibular morphology may have occurred. This speculation was further supported by the finding that mandibular length, measured without the condylar landmark, was 53.8% of predicted. During DO and early consolidation, the measures of bone density in the regenerates decreased compared to control for all groups. Thereafter, bone density in the regenerates generally increased in all groups until day 24 (P<0.01), obtaining levels that were comparable to the unoperated side. At both rostral and caudal sites adjacent to the osteotomies, measures of bone density were enhanced over control in all groups, with the rostral site also showing significant increases over time in the sham and the highest distraction groups (P<0.008 and P<0.014). We conclude that this rat model for mandibular distraction osteogenesis provides bone density changes that are consistent with those reported using larger animal protocols.

Analysis of Variance↗

New organosilicon maxillofacial prosthetic materials.

OBJECTIVES: The silicone elastomer A-2186 is a widely used maxillofacial prosthetic material. It is a pourable two-component silicone rubber cured by a platinum catalyst. Used as a prosthetic material, A-2186 has short working time and because of its hydrophobic nature, poor adhesion to non-silicone based adhesives. The purpose of this study is to evaluate the physical properties of new prosthetic materials based on methacryloxypropyl-terminated polydimethylsiloxane (MPDS-MF), and to compare the properties with those of A-2186. METHODS: Hardness, tensile strength, ultimate elongation, tear strength and adhesive bonding strength of MPDS-MF and A-2186 with and without additives were determined and compared. The bonding strengths of the extrinsic colorant carrier with the prosthetic materials were also determined. Statistical analyses were done using a two-way analysis of variance (ANOVA). For significant effects, post-hoc tests were done using the Bonferroni correction. RESULTS: The hardness of MPDS-MF is similar to A-2186. However, tensile strength, tear strength, ultimate elongation, and adhesive bonding strength of MPDS-MF are higher than those of A-2186. SIGNIFICANCE: MPDS-MF is cured by free radical thermal polymerization and crosslinking. The working time of MPDS-MF, unlike A-2186, is long. The presence of methacrylate groups in MPDS-MF enhances its adhesion to non-silicone based adhesive. Based on the present study, it appears that MPDS-MF is suitable for use in fabricating of clinical prostheses.

Adhesives↗

Reduced functional expression and molecular synthesis of inducible nitric oxide synthase in rostral ventrolateral medulla of spontaneously hypertensive rats.

BACKGROUND: We demonstrated recently that the prevalence of neuronal (nNOS) over inducible (iNOS) nitric oxide synthase activity at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic neurogenic vasomotor tone, and the associated dominance of sympathoexcitation over sympathoinhibition underlie the maintenance of sympathetic vasomotor outflow by the endogenous NO. Here, we evaluated the hypothesis that a significant downregulation of iNOS at the RVLM may play a crucial role in the genesis of augmented sympathetic vasomotor tone during hypertension. METHODS AND RESULTS: Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats anesthetized with propofol were used. Compared with SHR, the hypotension, bradycardia, or depression in sympathetic vasomotor tone induced by bilateral microinjection of lipopolysaccharide (5 or 10 ng) into the RVLM of WKY rats exhibited significantly shorter-onset latency, appreciably steeper slope, and a greater incidence of mortality. All these effects of lipopolysaccharide (10 ng) were significantly blunted by coadministration of the selective iNOS inhibitor S-methylisothiourea (250 pmol). Reverse transcription-polymerase chain reaction and Western blot analyses further revealed significantly lower iNOS mRNA and protein levels at the ventrolateral medulla in SHR under basal conditions or on activation by lipopolysaccharide (10 ng). Conversely, nNOS mRNA and protein levels remained constant in the RVLM and were comparable in both strains of rats. CONCLUSIONS: We conclude that a significant downregulation in both functional expression and molecular synthesis of iNOS at the RVLM may underlie the augmented sympathetic vasomotor tone during hypertension.

Animals↗

Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients.

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis characterized by a poikilodermatous rash starting in infancy, small stature, skeletal abnormalities, juvenile cataracts, and predisposition to specific cancers. We have identified a contemporary cohort of 41 patients to better define the clinical profile, diagnostic criteria, and management of patients with RTS. Patients with the diagnosis of RTS were ascertained by referrals from dermatology, ophthalmology, genetics, and oncology or from direct contact with the patient's family. Medical information was obtained from interviews with physicians, patients, and their parents and a review of medical records. The age range at ascertainment was 9 months to 42 years (28 males and 13 females; M:F, 2:1). All subjects displayed a characteristic rash. Thirteen subjects had osteosarcoma (OS) (32%), eight had radial defects (20%), seven had gastrointestinal findings (17%), two had cataracts (6%), and one had skin cancer (2%). Twenty-two of 28 patients without OS were less than 15 years old and thus remain at significant risk for this tumor. This case-series study reveals a clinical profile of RTS that includes a higher prevalence of OS and fewer cataracts, compared with historical reports. These differences may reflect either allelic or genetic heterogeneity. This study documents the frequency of clinical anomalies in a contemporary cohort of RTS patients and revises guidelines for diagnosis and management of RTS.

Adolescent↗

Uterine macrophages express the gp49B inhibitory receptor in midgestation.

Mouse gp49B is an immunoreceptor tyrosine-based inhibitory motif-bearing receptor identified on mast cells and NK cells. In this report, however, we show that this receptor is expressed on macrophages accumulating in the uterine metrial gland in midgestation, along with gp49A that has a very homologous extracellular domain with gp49B but has a short cytoplasmic domain without ITIM. Culture of bone marrow cells in the conditioned medium of the metrial gland resulted in the selective proliferation of macrophages expressing both Fcgamma-activating receptors and gp49B inhibitory receptor. Stimulation of macrophages with immobilized IgG, but not with anti-FcgammaRII/III, induced a considerable amount of TNF-alpha and IL-10 production, suggesting that the high-affinity receptor for IgG (FcgammaRI) can transmit activating signals in cytokine production of macrophages. Furthermore, coligation of gp49B with FcgammaRI resulted in the inhibition of TNF-alpha production. Thus, our data provide evidence that gp49B is an endogenous negative regulator of macrophage activation and may regulate the function of macrophages during pregnancy.

Animals↗

Fos protein is required for the re-expression of angiotensin II type 1 receptors in the nucleus tractus solitarii after baroreceptor activation in the rat.

We evaluated in Sprague--Dawley rats the hypothesis that Fos protein induced by baroreceptor activation in the nucleus tractus solitarii participates in transcriptional regulation of the expression of angiotensin receptor genes. Reverse transcription-polymerase chain reaction revealed that baroreceptor activation elicited by sustained hypertension resulted in a transient decrease in angiotensin II subtype 1, but not subtype 2, receptor messenger RNA, in the dorsomedial medulla, including the nucleus tractus solitarii. There was subsequently a transitory reduction in the pressor response elicited by microinjection bilaterally of angiotensin II (40 pmol) into the nucleus tractus solitarii, followed by an increase in c-fos messenger RNA and Fos immunoreactivity at the same nucleus. Both the re-expression of angiotensin II subtype 1 receptor messenger RNA and restoration of pressor response to angiotensin II after baroreceptor activation were significantly blunted by bilateral application into the nucleus tractus solitarii of an antisense oligonucleotide (50 pmol) that targets against the initiation codon of c-fos messenger RNA. Control pretreatment with the corresponding sense oligonucleotide (50 pmol), or an antisense c-fos oligonucleotide that targets against a different portion of the coding sequence of the c-fos messenger RNA (50 pmol), was ineffective. At the receptor level, the angiotensin II-induced pressor response was antagonized by the subtype 1 receptor antagonist losartan (1.6 nmol), but not by the subtype 2 receptor antagonist PD-123319 (1.6 nmol). These findings suggest that sustained hypertension down-regulates angiotensin II subtype 1 receptors at both messenger RNA and functional expression levels in the nucleus tractus solitarii. Furthermore, Fos protein induced in the nucleus tractus solitarii by baroreceptor activation may play a permissive role in the transcriptional regulation of the re-expression of this subtype of angiotensin receptors.

Angiotensin II↗

Differential cardiovascular responses to blockade of nNOS or iNOS in rostral ventrolateral medulla of the rat.

We investigated the contribution of neuronal or inducible nitric oxide synthase (nNOS or iNOS) at the rostral ventrolateral medulla (RVLM) to central cardiovascular regulation by endogenous nitric oxide (NO), using Sprague-Dawley rats anaesthetized and maintained with propofol. Microinjection bilaterally into the RVLM of a NO trapping agent, carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-l-oxy-l-3-oxide (10, 50 or 100 nmoles) resulted in significant hypotension and bradycardia. Similar application of a selective antagonist of nNOS, 7-nitroindazole (1, 2.5 or 5 pmoles), or selective antagonists of iNOS, aminoguanidine (125, 250 or 500 pmoles), N(6)-(l-iminoethyl)-L-lysine (250 pmoles) or S-methylisothiourea (250 pmoles), induced respectively a reduction or an enhancement in systemic arterial pressure, heart rate and power density of the vasomotor components in the spectrum of arterial blood pressure signals, the experimental index for sympathetic neurogenic vasomotor tone. Both hypotension and bradycardia induced by the NO precursor, L-arginine (100 nmoles), were significantly blunted when aminoguanidine (250 pmoles) was co-microinjected bilaterally into the RVLM. On the other hand, co-administered 7-nitroindazole (2.5 pmoles) was ineffective. Whereas low doses of S-nitro-N-acetylpenicillamine (0.25 or 0.5 nmoles) elicited hypertension and tachycardia, high doses of this non-nitrate NO donor (5 nmoles) induced hypotension and bradycardia. Reverse transcription - polymerase chain reaction analysis revealed that both iNOS and nNOS mRNA were expressed in the ventrolateral medulla. We conclude that the prevalence of nNOS over iNOS activity at the RVLM and the associated dominance of sympathoexcitation over sympathoinhibition may underlie the maintenance of sympathetic vasomotor outflow and stable systemic arterial pressure by the endogenous NO.

Animals↗

[Analysis of main chemical composition in hydrogenated rosin from Zhuzhou].

The acid fraction, the main part of the hydrogenated rosin produced by Zhuzhou Forest Chemicals Plant of China, was separated from neutral fraction by modified DEAE-Sephadex ion exchange chromatography and analyzed with GC-MS-DS technique by using DB-5 capillary column. Six dihydroabietic-type resin acids, four dihydropimaric/isopimaric-type resin acids and four tetrahydroabietic-type resin acids were identified. The hydrogenated rosin is composed mainly of 8-abietenoic acid, 18-abietanoic acid, 13-abietenoic acid, 8 alpha, 13 beta-abietanoic acid, 13 beta-8-abietenoic acid and 8-isopimarenoic acid etc.

Carboxylic Acids↗

[Effects of interleukin-2 on the isolated rat heart and the mechanism].

The purpose of the present study was to explore the biological effects and mechanism of interleukin-2 (IL-2) on the isolated rat heart. The results showed that hrIL-2 increased the number of premature ventricular contraction, heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow in the isolated perfused rat heart. Heat inactivated hrIL-2 had no effect on the heart. Pretreatment with ryanodine canceled the positive effects of hrIL-2 on left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow but had no effects on arrhythmogenesis and tachycardia by hrIL-2. Pretreatment with nifedipine or low extracellular calcium abolished the arrhythmogenic effect of hrIL-2 and attenuated partially the augment of heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow. It suggests that the cardiac activity of hrIL-2 depended on the integrity of its spatial structure and transmembrane influx Ca2+ and intracellularly stored Ca2+ were involved in the cardiac activity of hrIL-2.

Animals↗

[Effect of shenqi fuzheng injection on immune function in gastric carcinoma patients in post-operational and chemotherapeutic period].

OBJECTIVE: To investigate the effect of Shenqi Fuzheng injection (SQFZI) on immune function in gastric carcinoma patients in post-operational and chemotherapeutic period. METHODS: One hundred and twenty-three gastric carcinoma post-operational patients and 36 cases of gastric carcinoma patients on chemotherapy, according to their using SQFZI or not, parameters of immune function, including red blood cell C3b receptor rosette (RBC-C3bRR) and immune complex rosette (RBC-ICR), T-lymphocyte subsets and NK cell activity were determined. RESULTS: RBC-C3bRR, CD3, CD4 and NK cell activity were significantly higher, but RBC-ICR was lower in patients of post-operational period treated with SQFZI than those in patients untreated with SQFZI (P < 0.01). The same difference also revealed between the patients in chemotherapeutic period treated and untreated with SQFZI (P < 0.01). CONCLUSION: The immune function of gastric carcinoma patients in post-operational or chemotherapeutic period could be effectively improved by addition of SQFZI.

Adjuvants, Immunologic↗

The SCAN domain mediates selective oligomerization.

The SCAN domain is described as a highly conserved, leucine-rich motif of approximately 60 amino acids found at the amino-terminal end of zinc finger transcription factors. Although no specific biological function has been attributed to the SCAN domain, its predicted amphipathic secondary structure led to the suggestion that this domain may mediate protein-protein associations. A yeast two-hybrid screen identified members of two SCAN domain protein families that interact with the SCAN domain of the zinc finger protein ZNF202. The interacting ZNF191 protein represents the family of SCAN domain-containing zinc finger proteins, whereas the novel SDP1 protein establishes a new family of genes that encode an isolated SCAN domain. Isolated SCAN domain proteins may form asymmetric homodimers in solution. Biochemical binding studies confirmed the associations of ZNF191 and SDP1 with ZNF202 and established the SCAN domain as a selective hetero- and homotypic oligomerization domain. SCAN mediated protein associations might therefore represent a new regulatory mechanism of transcriptional activity.

Amino Acid Sequence↗

Inducible expression of the gp49B inhibitory receptor on NK cells.

Murine NK cells express inhibitory receptors belonging to the C-type lectin-like (Ly-49, CD94/NKG2) and Ig superfamily-related (gp49) receptors. The murine gp49B receptor displays structural homology with human killer inhibitory receptors, and was previously identified to be a receptor on mast cells and activated NK cells. The gp49B receptor is highly related to gp49A, a receptor with unknown function. In this study, using a novel mAb produced against soluble gp49B molecules that cross-reacts with gp49A, we examined the cellular distribution and function of these receptors. gp49 is constitutively expressed on cells of the myeloid lineage throughout development, as well as on mature cells. Importantly, gp49 is not expressed on spleen- and liver-derived lymphocytes, including NK cells, but its expression is induced in vitro on NK cells following IL-2 stimulation, or in vivo by infection with murine CMV. Molecular studies revealed that both the immunoreceptor tyrosine-based inhibitory motif-containing gp49B as well as immunoreceptor tyrosine-based inhibitory motif-less gp49A receptors are up-regulated on NK cells following murine CMV infection. When co-cross-linked with NK1.1, gp49B can inhibit NK1.1-mediated cytokine release by NK cells. Taken together, these studies demonstrate that the expression of gp49B on NK cells is regulated, providing the first example of an in vivo activation-induced NK cell inhibitory receptor, in contrast to the constitutively expressed Ly49 family.

Amino Acid Motifs↗

Nonstochastic coexpression of activation receptors on murine natural killer cells.

Murine natural killer cells (NK) express lectin-like activation and inhibitory receptors, including the CD94/NKG2 family of receptors that bind Qa-1, and the Ly-49 family that recognizes major histocompatibility complex class I molecules. Here, we demonstrate that cross-linking of NK cells with a new specific anti-Ly-49H mAb induced NK cell cytotoxicity and cytokine production. Ly-49H is expressed on a subset of NK cells and can be coexpressed with Ly-49 inhibitory receptors. However, unlike Ly-49 inhibitory receptors, Ly-49H is not detectable on naive splenic CD3(+) T cells, indicating that Ly-49H may be an NK cell-specific activation receptor. In further contrast to the stochastically expressed Ly-49 inhibitory receptors, Ly-49H is preferentially expressed with the Ly-49D activation receptor, and expression of both Ly-49H and Ly-49D is augmented on NK cells that lack receptors for Qa-1 tetramers. On developing splenic NK1.1(+) cells, Ly-49D and Ly-49H are expressed later than the inhibitory receptors. These results directly demonstrate that Ly-49H activates primary NK cells, and suggest that expression of Ly-49 activation receptors by NK cells may be specifically regulated on NK cell subsets. The simultaneous expression of multiple activation receptors by individual NK cells contrasts with that of T cell antigen receptors and is relevant to the role of NK cells in innate immunity.

Animals↗