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Biomedical subjects

T Tang

Publications and source records attributed to T Tang.

At least 55 records · Page 3Linked to original sources

The effect of thyrotropin receptor antibodies on the proliferation of FRTL-5 cells and the expression of protooncogene c-fos mRNA.

OBJECTIVE: Hyperthyroidism and a diffuse goiter are the main symptoms of Graves' disease (GD) associated with autoantibodies to thyroid-stimulating hormone (TSH) receptor (TRAb). The present study was conducted to evaluate effects of autoantibodies in patients with GD (TRAb-IgG) on induction of the proliferation and c-fos mRNA expression in FRTL-5 cells (Fisher rat thyroid cell line). METHODS: Highly purified IgG fractions were isolated from 11 patients with GD, TRAb-IgG and 15 normal individuals (normal controls) with Protein A Sepharose CL-4B affinity column chromatograph. FRTL-5 cells, which had been grown to subconfluency and deprived of TSH for a few days. Then, these cells were used for measuring cAMP content, 3H-thymidine incorporation in cells and the expression of c-fos mRNA respectively. RESULTS: After stimulation of TRAb-IgG, the cAMP production and 3H-thymidine incorporation in FRTL-5 cells were much higher than those from normal controls (P < 0.05 respectively). Using 32P labelled v-fos probe by the Northern Blot method, the expression of c-fos mRNA could be induced by IgGs from patients with GD. CONCLUSIONS: These data suggest that the stimulation of TRAb-IgG followed by cAMP production and 3H-thymidine incorporation is related to the induction of c-fos mRNA and, thus, to the growth of FRTL-5 cells.

Animals↗

[Diagnosis and treatment of tuberculous appendicitis].

OBJECTIVE: To study the diagnosis and treatment of tuberculous appendicitis. METHOD: 12 cases (0.26%) with tuberculous appendicitis diagnosed by histopathological examination selected from 4,652 patients during 1968 to 1997 were analysed retrospectively. RESULT: The mean age of the patients with tuberculous appendicitis was 35 years, the disease occurred 2 times more frequently in women than in men and was usually secondary to tuberculosis elsewhere in the body (7 cases). There were 7 cases with proliferative lesions, 3 cases with ulcerative lesions and 2 cases with two kinds of lesions. 12 cases were all misdiagnosed preoperatively, 2 cases were diagnosed definitely in the operation. In 12 cases, 7 cases underwent simple appendectomy, 2 cases partial celectomy and 1 case right hemicolectomy, appendectomy and resection of regional lymph nodes were performed on 2 cases, treatment of anti-TB was given postoperatively to 9 patients. All the patients recovered without complications. CONCLUSION: It's hard to get definite diagnosis of tuberculous appendicitis before operation because of low incidence and non-specific clinical manifestations, so careful observation in the operation and routine histopathological examination must be emphasized. Early operation and postoperative treatment of anti-TB should be advocated in order to prevent from complications.

Adult↗

[Incorporation of cortical allograft: a biomechanical study].

OBJECTIVE: To explore the changes of biomechanical properties of cortical allograft in different mechanical environments. METHOD: Cortical allograft was transplanted to each side of the midshaft diaphyseal ulnar of 40 rabbits. The left transplanted allograft underwent normal physiological load, while the right underwent lower load. Animals were killed and specimens taken for examination of bone mineral density, bone porosity and maximal three-point-bend breaking load. RESULT: The union strength of allograft-host bone junction increased constantly, while the internal creeping substitution led to an initial greater weakening of the cortical allograft itself and the later recovery of its strength. In comparison, the union strength of the normally loaded graft-host surface was significantly higher than that of the lower loaded side at eight and sixteen weeks after transplantation. At the sixteenth week, there was greater bone strength in normally loaded graft than that in less loaded graft. CONCLUSION: The internal repair would lead to initial greater weakening of cortical allograft and the later gradual recovery of its strength. The effect of physiological load can accelerate the improvement of the biomechanical properties of allograft.

Animals↗

Care of elderly patients with DNR orders in Singapore--a descriptive study.

OBJECTIVE: To describe the demographic profile of a cohort of elderly patients with a 'do-not-resuscitate' (DNR) order at death and to study the specific supportive measures instituted or withdrawn during the DNR period and those in force at the time of death. METHODS: The case notes of patients who died between October 1996 and March 1997 in the Department of Geriatrics, Alexandra Hospital were studied retrospectively by a single observer. RESULTS: Only 95 out of an eligible 102 patients' case notes could be retrieved. Seventy-two (75.8%) patients had a DNR status at death. The racial distribution was as follows: 90.3% Chinese, 5.6% Indians, 2.8% Malays and 1.4% Others while their pre-admission domicile were: own home 79.2%, nursing home 19.4% others 1.4%. Those bedbound constituted 48.6% of the cohort while 29.2% had dementia and 43.1% were totally dependent for their activities of daily living. The commonest cause of death was pneumonia while the average duration patients were on the DNR status was 5.1 days before death. The commonest measures instituted during DNR period were as follows: oxygen therapy (38.9%), nasogastric tube insertion and feeding (30.6% and 33.3% respectively), intravenous fluid administration (33.3%), blood investigations (33.3%), opioid use (33.3%) and antibiotic use (29.2%). Measures withdrawn were intravenous fluid administration (36.1%), hourly monitoring of parameters (22.2%), antibiotics (13.9%), high dependency care (12.5%) and nasogastric tube feeding (6.9%). CONCLUSION: The DNR status is decided late in the course of a patient's illness when he may have been too ill to partake in the decision making process. Even if a DNR status was ordered, a patient might still be subjected to CPR at death.

Aged↗

A role for Mac-1 (CDIIb/CD18) in immune complex-stimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fcgamma receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis.

Mac-1 (alphambeta2), a leukocyte adhesion receptor, has been shown in vitro to functionally interact with Fcgamma receptors to facilitate immune complex (IC)-stimulated polymorphonuclear neutrophil (PMN) functions. To investigate the relevance of Mac-1-FcgammaR interactions in IC-mediated injury in vivo, we induced a model of Fc-dependent anti-glomerular basement membrane (GBM) nephritis in wild-type and Mac-1-deficient mice by the intravenous injection of anti-GBM antibody. The initial glomerular PMN accumulation was equivalent in Mac-1 null and wild-type mice, but thereafter increased in wild-type and decreased in mutant mice. The absence of Mac-1 interactions with obvious ligands, intercellular adhesion molecule 1 (ICAM-1), and C3 complement, is not responsible for the decrease in neutrophil accumulation in Mac-1- deficient mice since glomerular PMN accumulation in mice deficient in these ligands was comparable to those in wild-type mice. In vitro studies showed that spreading of Mac-1-null PMNs to IC-coated dishes was equivalent to that of wild-type PMNs at 5-12 min but was markedly reduced thereafter, and was associated with an inability of mutant neutrophils to redistribute filamentous actin. This suggests that in vivo, Mac-1 is not required for the initiation of Fc-mediated PMN recruitment but that Mac-1-FcgammaR interactions are required for filamentous actin reorganization leading to sustained PMN adhesion, and this represents the first demonstration of the relevance of Mac-1-FcgammaR interactions in vivo. PMN-dependent proteinuria, maximal in wild-type mice at 8 h, was absent in Mac-1 mutant mice at all time points. Complement C3-deficient mice also had significantly decreased proteinuria compared to wild-type mice. Since Mac-1 on PMNs is the principal ligand for ic3b, an absence of Mac-1 interaction with C3 probably contributed to the abrogation of proteinuria in Mac-1-null mice.

Actins↗

Clinical potential of microchip capillary electrophoresis systems.

Clinical interest in the use of capillary electrophoresis (CE) has recently been extended to the microchip environment. Clinical analyses demand careful handling of complex samples that are often limited in quantity and in concentration. The integrated sample handling and analysis capabilities of microchip substrates thus seem ideally suited to clinical applications. This review surveys the development of sample handling (injection, mixing, and reaction) and separation elements on-chip. The integration of these elements to create a variety of clinical analyzers has been demonstrated. The application of microchip CE systems to human serum protein analysis, immunoassay, and DNA studies is reviewed, along with various other clinical applications. In addition, the clinical potential of the lab-on-a-chip concept is discussed.

Blood Proteins↗

Diversity associated with the second expressed HLA-DRB locus in the human population.

Although diversity within the HLA-DRB region is predominantly focused in the DRB1 gene, the second expressed DRB loci, DRB3, DRB4, and DRB5, also exhibit variation. Within DRB1(*)15 or DRB1(*)16 haplotypes, four new variants were identified: 1) two new DRB5 alleles, DRB5*0104 and DRB5*0204, 2) a haplotype carrying a DRB1(*)15 or *16 allele without the usual accompanying DRB5 allele, and 3) a haplotype carrying a DRB5(*)0101 allele without a DRB1(*)15 or *16 allele. The evolutionary origins of these haplotypes were postulated based on their associations with the DRB6 pseudogene. Within HLA haplotypes which carry DRB3, a new DRB3(*)0205 allele and one unusual DRB3 association were identified. Finally, two new null DRB4 alleles are described: DRB4(*)0201N, which exhibits a deletion in the second exon, and a second allele, DRB4(*)null, which lacks the second exon completely. Gene conversion-like events and variation in the number of functional genes through reciprocal recombination and inactivation contribute to the diversity observed in the second expressed HLA-DRB loci.

Alleles↗

Mechanisms of action of anti-GM1 and anti-GQ1b ganglioside antibodies in Guillain-Barré syndrome.

Anti-GM1 and anti-GQ1b ganglioside antibodies are found in association with acute and chronic peripheral neuropathies, including Guillain-Barré syndrome. They are believed to arise as a result of molecular mimicry with immunogenic microbial polysaccharides. Although anti-ganglioside antibodies are suspected to play a causal role in neuropathy pathogenesis, the details of this have yet to be proven. The approach in this laboratory to solving this issue has been to generate anti-GM1 and anti-GQ1b monoclonal antibodies from peripheral blood lymphocytes of affected patients and to study their immunolocalization in peripheral nerve and their electrophysiologic effects in animal models in which peripheral nerve sites are exposed to anti-ganglioside antibodies. These data show that anti-ganglioside antibody-reactive epitopes are widely distributed in peripheral nerve and can cause electrophysiologic abnormalities in a variety of model systems; thus, these data support the view that anti-ganglioside antibody-reactive epitopes may directly contribute to neuropathy pathogenesis.

Animals↗

Identification of four new DR52-associated DRB1 alleles: DRB1*1424, *1425, *1323 and *1324.

Four previously unreported DR52-associated DRB1 alleles have been characterized through DNA sequencing, contributing to the diversity of the HLA system. DRB1*1424 is nearly identical to DRB1*1402 in the second exon, except that it contains the "I---A" motif found at codons 67-71 common to the DRB1*15 alleles. DRB1*1425 contains the "A--H" motif, found in DRB1*1401 at codons 57-60, in a sequence otherwise identical with the second exon of DRB1*1307. Compared with DRB1*11012, DRB1*1323 contains three predicted amino acid changes at codons 58 (ala-->glu), 67 (phe-->ile), and 71 (arg-->glu). The sequence of DRB1*1324 is identical to exon 2 of DRB1*1103, except that DRB1*1324 does not contain the GAG at codon 58 characteristic of the DRB1*11 alleles. These new alleles may have arisen through gene conversion, and they contribute to the complexity of the DR6 family.

Alleles↗

[Operative treatment of displaced acetabular fractures through the ilioinguinal approach].

To reduce the incidence of ectopic ossification and improve hip joint function after the operative treatment of displaced acetabulum fractures. We surgically treated 12 acetabular fractures which involved anterior column or both anterior and posterior column fractures through the ilioinguinal approach. 10 patients were judged postoperatively to have an anatomic reduction, and 2 had a satisfactory reduction. An average of 3-year follow-up showed excellent results in 8 patients (67%) and good in 4 (33%). Radiographic results indicated excellent results in 8 (67%), patients good in 3 (25%), fair in 1 (8%). The results suggested that the ilioinguinal approach appears to diminish many of the problems associated with utilization of an extrapelvic approach, including the disturbances of the hip abductor system, heterotopic ossification, sciatic palsy, the slow recovery of hip mobility. We conclude that it is not only good for an operative treatment of anterior column fractures but also good for some of posterior column fractures.

Acetabulum↗

[Investigation on matrix degrading enzymes of lumbar intervertebral discs].

Changes in the macromolecular matrix of the intervertebral disc may predispose to biomechanical failure of the disc. Such changes would involve extracellular enzymes capable of altering the collagen and proteoglycan of the disc matrix. In this study, tritium-labeled type I collagen was used as a substrate to estimate the activity of collagenase in the discs of 41 cases of lumbar disc protrusion (LDP) patients by surgical intervention. The annulus fibrous (AF) and nucleus pulposus (NP) were measured separately. 34 normal discs harvested by autopsy acted as controls. For estimation of relative neutral proteinase content of 6 normal and 16 degenerated lumbar discs, polyacrylamide gelelectrophoresis (PAGE), heat-denatured collagen as a substrate, and photo-density scanning with peak area autocalculating system were adopted. The results presented that both AF and NP of the normal discs had a similar lower collagenolytic activity and a very limited activity of neutral proteinase, while the degenerated discs showed a higher activity, especially in the degenerated NP. The extruded type of LDP got a higher collagenolytic activity in NP than that of the prolapsed LDP. The fact showed that the matrix degrading enzymes play a very important role in the process of lumbar disc degeneration. The difference of disc degeneration is the biochemical basis of different clinical types of LDP. Matrix degrading enzyme system is a very complexed multienzymatic system. Other neutral proteinases may join this system besides the collagenase.

Adolescent↗

Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins.

Leukocyte accumulation in cerebrospinal fluid and disruption of the blood-brain barrier are central components of meningitis and are associated with a poor prognosis. Genetically engineered deficiencies or functional inhibition of endothelial leukocyte adhesion receptors P-, or P- plus E-selectins, lead to deficits in leukocyte rolling and extravasation. However, their impact on meningeal inflammation has not been tested previously. An acute cytokine-induced meningitis model associated with significant cerebrospinal fluid leukocyte accumulation (averaging 14,000 leukocytes/microl as early as 4 h) and blood-brain barrier permeability was developed in adult mice. This model was applied to mice deficient in P-selectin and mice doubly deficient in P- and E-selectins. Partial inhibition of cerebrospinal fluid leukocyte influx and permeability was noted in P-selectin-deficient mice. Mice doubly deficient in P- and E-selectins displayed a near complete inhibition of these parameters. Our results suggest that P- and E-selectins cooperatively contribute to meningitis and that functional blocking of both endothelial selectins in conjunction with antibiotics may provide a therapeutic approach for treatment of bacterial meningitis.

Animals↗

Opioid regulation of intracellular free calcium in cultured mouse dorsal root ganglion neurons.

Opioid agonists induced an increase in the intracellular free calcium concentration ([Ca2+]i) or an inhibition of K+ (25 mM)-stimulated increase in [Ca2+]i in different subsets of mouse dorsal root ganglion (DRG) neurons. The total neuronal population was grouped into three classes according to somatic diameter and defined as small ( < 16 microns), intermediate (16-25 microns), or large ( > 25 microns) neurons. Substance P-like immunoreactivity was detected mainly in the small and intermediate neurons. The delta, kappa, and mu opioid receptor agonists [D-Ser2,Leu5]enkephalin-Thr (DSLET), U69593, and [D-Ala2, MePhe4, Glyol5]enkephalin (DAMGO) each induced a transient increase in [Ca2+]i in a small fraction ( < 30%) of neurons. The increases in [Ca2+]i were blocked by the opioid antagonist naloxone. The dihydropyridine-sensitive calcium channel blocker nifedipine also blocked the increase in [Ca2+]i induced by 1 microM DSLET. The rank order of potency (percentage of cells responding to each opioid agonist) was DSLET > U69593 > DAMGO. The opioid-induced increase in [Ca2+]i was observed mainly in large neurons, with a low incidence in small and intermediate neurons. Opioid agonists also caused inhibition of K(+)-stimulated increases in [Ca2+]i, which were blocked by naloxone (1 microM). Inhibition of the K(+)-stimulated increase by 1 microM DSLET or U69593 was greater in small and intermediate neurons than in large neurons.

Analgesics↗

A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

IgM paraproteins associated with autoimmune peripheral neuropathy and anti-Pr cold agglutinins react with sialic acid epitopes present on disialylated gangliosides including GD1b, GT1b, GQ1b, and GD3. A causal relationship between the paraprotein and the neuropathy has never been proven experimentally. From peripheral blood B cells of an affected patient, we have cloned a human hybridoma secreting an antidisialosyl IgM mAb, termed Ha1, that shows identical structural and functional characteristics to its serum counterpart. Variable region analysis shows Ha1 is encoded by the same VH1 family heavy chain gene, V1-18, as the only other known anti-Pr antibody sequence and is somatically mutated, suggesting that it [correction of is] arose in vivo in response to antigenic stimulation. In the rodent peripheral nervous system, Ha1 immunolocalizes to dorsal root ganglia, motor nerve terminals, muscle spindles, myelinated axons, and nodes of Ranvier. After intraperitoneal injection of affinity-purified antibody into mice for 10 d, electrophysiological recordings from the phrenic nerve-hemidiaphragm preparation demonstrated impairment of nerve excitability and a reduction in quantal release of neurotransmitter. These data unequivocally establish that an antidisialosyl antibody can exert pathophysiological effects on the peripheral nervous system and strongly support the view that the antibody contributes to the associated human disease.

Amino Acid Sequence↗

Acute passive anti-glomerular basement membrane nephritis in P-selectin-deficient mice.

P-selectin present on surfaces of activated endothelium and platelets mediates neutrophil-endothelial and neutrophilplatelet interactions. The role of P-selectin in vivo was examined in a model of acute passive anti-GBM nephritis in P-selectin-deficient and wild-type mice which was induced by intravenous injection of anti-GBM serum. There were two major differences between P-selectin-deficient and wild-type mice. Firstly, mutant mice had approximately two fold more glomerular PMNs and albuminuria than wild-type animals at the peak of neutrophil influx and proteinuria. Secondly, Lipoxin A4 (LXA4), an eicosanoid which inhibits leukocyte-endothelial adhesion in vitro, and is generated primarily by transcellular biosynthetic routes during P-selectin-mediated platelet-PMN interaction [1], was approximately 60% of wild type levels in nephritic kidneys of P-selectin-deficient mice. Injection of wild-type platelets into P-selectin-null mice restored LXA4 to wild-type levels. The corresponding PMN influx approximated PMN levels in wild-type mice receiving platelets but urine albuminuria remained higher. Although these two P-selectin-dependent events cannot be directly linked, our results point to the importance of considering both platelet and endothelial P-selectin in determining the cellular events in inflammation.

Acute Disease↗

Nerve growth factor-stimulated nuclear S6 kinase in PC12 cells.

Previous work has shown that nerve growth factor (NGF) stimulates the phosphorylation of the ribosomal protein S6 in PC12 cells. In this study, we show that S6 kinase activity is also present in purified PC12 cell nuclei. This activity was increased by treatment of the cells with NGF and, to a lesser extent, by treatment with epidermal growth factor. The NGF-stimulated activity was obtained from nuclear extracts and some of its characteristics described. The increase in activity was prevented by treatment of the cells with rapamycin or with wortmannin, and the overall activity could be precipitated by antibodies directed against the p85SGK. These data indicate that p85SGK is the NGF-stimulated S6 kinase in PC12 cell nuclei. The presence of S6 protein in the nucleus of PC12 cells has been confirmed and evidence is presented that suggests that it is identical to a protein called SMP reported some years ago.

Amino Acid Sequence↗

Temporal differences in the phosphorylation state of pre- and postsynaptic protein kinase C substrates B-50/GAP-43 and neurogranin during long-term potentiation.

The phosphorylation state of two identified neuralspecific protein kinase C substrates (the presynaptic protein B-50 and the postsynaptic protein neurogranin) was monitored after the induction of long term potentiation in the CA1 field of rat hippocampus slices by quantitative immunoprecipitation following 32Pi labeling in the recording chamber. B-50 phosphorylation was increased from 10 to 60 min, but no longer at 90 min after long term potentiation had been induced, neurogranin phosphorylation only at 60 min. Increased phosphorylation was not found when long term potentiation was blocked with the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovalerate, when only low frequency stimulation was applied or tetanic stimulation failed to induce long term-potentiation. Our data show that both B-50 and neurogranin phosphorylation are increased following the induction of long term potentiation, thus providing strong evidence for pre- and postsynaptic protein kinase C activation during narrow, partially overlapping, time windows after the induction of long term potentiation.

Animals↗

Anaesthetic management of a patient with a descending thoracic aortic aneurysm and severe bilateral bullous pulmonary parenchymal disease.

The anaesthetic management of the surgical repair of a descending aortic aneurysm in a patient with large, bilateral, pulmonary bullae is described. Anaesthesia for descending aortic surgery normally involves unilateral, positive-pressure ventilation, an option which poses some risk of barotrauma in the presence of bilateral bullae. Patients with bullous disease commonly have severe lung disease and thorough preoperative assessment and preparation are necessary. Intraoperatively, bilateral rupture of the bullae could be catastrophic and preparations should be made for this possibility. In order to diminish this risk, a surgical technique including preemptive collapse of the bulla by minithoracotomy and tube drainage, with use of a bronchial blocker to the affected part of the lung may be used. If rupture occurs, then high frequency jet ventilation may be effective. Use of a double lumen endobronchial tube may be advantageous for patients with either unilateral and bilateral bullae. Anaesthesia for patients with bullae should avoid positive-pressure ventilation and nitrous oxide in order to limit the risk of barotrauma from a ball valve mechanism. In this case, the risk of barotrauma was reduced by performing an inhalational induction of anaesthesia and limiting peak inflation pressures during thoracotomy. It was elected to use positive-pressure ventilation through a double lumen endobronchial tube following chest incision. A high frequency jet ventilator was available but not employed. Anaesthetic management was complicated by the presence of pleural adhesions, surgical approach directly through a bulla, and the requirement for one lung ventilation.

Adult↗