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Biomedical subjects

T Tang

Publications and source records attributed to T Tang.

At least 91 records · Page 5Linked to original sources

Opioids acting through delta receptors elicit a transient increase in the intracellular free calcium concentration in dorsal root ganglion-neuroblastoma hybrid ND8-47 cells.

The neuronal cell line ND8-47 (neuroblastoma x dorsal root ganglion neuron hybrid) expressed opioid delta-type receptors. We report opioid-induced changes in cytosolic intracellular free calcium ([Ca++]i) in differentiated ND8-47 cells. Delta-opioid receptor agonists induced a transient (< 2 min) increase in [Ca++]i in a concentration-dependent fashion with the potency order: [D-Ser2,Leu5]enkephalin-Thr (DSLET) > or = deltorphin II > [D-Pen2,5] enkephalin. Their effects were blocked by naloxone (IC50 = 20 nM) and naltrindole (IC50 = 2.5 nM). Selective mu and kappa receptor agonists had no effect on [Ca++]i. The subtype specific delta receptor antagonists, 7-benzylidene naltrexone (delta-1) and naltriben (delta-2), were used to characterize further the subtype of delta receptors mediated by this response. Naltriben was more potent than 7-benzylidene naltrexone in antagonizing the DSLET-induced increase in [Ca++]i. The increase in [Ca++]i induced by DSLET was blocked by nifedipine (1 microM) or verapamil (1 microM), and was not observed in the absence of external calcium. Changes in [Ca++]i also were measured in single ND8-47 cells. The percentage of cells responding to DSLET (1 microM), deltorphin-II (1 microM) and [D-Pen2,5]enkephalin (1 microM) were 86, 84 and 37%, respectively. The results suggest that an increase in [Ca++]i induced by opioids is mediated through opioid delta receptors which can activate dihydropyridine-sensitive Ca++ channels.

Analgesics↗

ZNC(C)PR affects developmental changes of P46 phosphorylation in rat hippocampus.

Protein phosphorylation has been suggested to be correlated with brain development and with the molecular mechanism of behavioral effects of neuropeptides. The present study reports in vitro endogenous phosphorylation of P46, a membrane-associated protein that is changed during development of the rat hippocampus. This study indicated that the degree of endogenous phosphorylation may be correlated with the establishment of synaptic connections. Interestingly, P46 was proved to be identical to a well-known growth-associated protein B-50/GAP-43 in its identical apparent molecular weight, isoelectric point, phosphorylation dependence, and the cross immunoreaction of monoclonal anti-B-50/GAP-43 antibody and P46. Moreover, neonatal administration of neuropeptide ZNC(C)PR could facilitate the developmental progress of P46 endogenous phosphorylation. It is suggested that the changes in P46 phosphorylation could be involved in the cellular mechanism of ZNC(C)PR behavioral effects on learning.

Animals↗

Retinoic acid induction of major histocompatibility complex class I genes in NTera-2 embryonal carcinoma cells involves induction of NF-kappa B (p50-p65) and retinoic acid receptor beta-retinoid X receptor beta heterodimers.

Retinoic acid (RA) treatment of human embryonal carcinoma (EC) NTera-2 (NT2) cells induces expression of major histocompatibility complex (MHC) class I and beta-2 microglobulin surface molecules. We found that this induction was accompanied by increased levels of MHC class I mRNA, which was attributable to the activation of the two conserved upstream enhancers, region I (NF-kappa B like) and region II. This activation coincided with the induction of nuclear factor binding activities specific for the two enhancers. Region I binding activity was not present in undifferentiated NT2 cells, but binding of an NF-kappa B heterodimer, p50-p65, was induced following RA treatment. The p50-p65 heterodimer was produced as a result of de novo induction of p50 and p65 mRNAs. Region II binding activity was present in undifferentiated cells at low levels but was greatly augmented by RA treatment because of activation of a nuclear hormone receptor heterodimer composed of the retinoid X receptor (RXR beta) and the RA receptor (RAR beta). The RXR beta-RAR beta heterodimer also bound RA responsive elements present in other genes which are likely to be involved in RA triggering of EC cell differentiation. Furthermore, transfection of p50 and p65 into undifferentiated NT2 cells synergistically activated region I-dependent MHC class I reporter activity. A similar increase in MHC class I reporter activity was demonstrated by cotransfection of RXR beta and RAR beta. These data show that following RA treatment, heterodimers of two transcription factor families are induced to bind to the MHC enhancers, which at least partly accounts for RA induction of MHC class I expression in NT2 EC cells.

Animals↗

Möbius syndrome: evidence for a vascular etiology.

We report five infants with restricted lateral gaze, facial diplegia, feeding difficulty, and/or respiratory disorders without significant pulmonary disease. Viral studies were negative in all patients. Two children had radiologic findings that included brain-stem hypoplasia and symmetric calcification in the dorsal tectum at the junction of the midbrain and pons. Autopsy of one of these two children demonstrated capillary telangiectasia in the mesencephalon and pons. The other three children had normal computed tomographic (CT) scans. However, their autopsies revealed focal brain-stem necrosis with calcifications but without vascular malformation. We suggest that the capillary malformations in one of our patients directly resulted in a vascular-induced necrosis and the manifestation of Möbius sequence. The similarity of symmetric neuropathologic findings in the three other patients and the CT scan in the one surviving patient suggest focal hemodynamic changes restricted to the posterior circulation, indirectly supporting a vascular theory of embryopathogenesis.

Brain Diseases↗

Hyperselective posterior rhizotomy in treatment of spasticity of paralytic limbs.

One hundred and eight patients with spasticity of the paralytic limbs were treated successfully with hyperselective posterior rhizotomy (SPR). Of the 108 patients, 100 had cerebral palsy, 2 hemiplegia, 3 sequelae of cerebral injury, 2 paraplegia and 1 multiple sclerosis. Twelve patients received cervical SPR and 96 lumbosacral SPR. Laminectomy is performed to open the dura and to separate the posterior spinal root into several rootlets. The lower threshold rootlets were divided after electrical stimulation. Follow-up for 6 to 30 months showed that the effective rate of reducing spasticity was over 95% and functional improvement rate over 80%.

Adolescent↗

[3,4-Diaminopyridine-evoked norepinephrine release and B-50 (GAP-43) phosphorylation].

3,4-Diaminopyridine (3,4-DAP 100 mumol.L-1) evoked [3H]norepinephrine ([3H]NE) release in rat hippocampal slices preincubated with [3H]NE and superfused with medium with or without Ca2+. Phorbolester 4 beta-phorbol 12, 13, dibutyrate 1 mumol.L-1) enhanced and polymyxin B (100 mumol.L-1) inhibited the release of [3H]NE under both conditions. The neuron-specific protein B-50 is a major presynaptic substrate of protein kinase C and involved in exocytosis. Using in situ protein phosphorylation analyzed by SDS-PAGE and autoradiography, we observed that B-50 phosphorylation was significantly decreased by 3,4-DAP in the presence of extracellular Ca2+ and completely inhibited by removal of extracellular Ca2+. It was suggested that B-50 phosphorylation was not involved in 3,4-DAP-evoked [3H]NE release.

4-Aminopyridine↗

Differential role of endothelial function on vasodilator responses in series-arranged arterioles.

Both in vitro and in vivo studies have revealed that removal of vascular endothelial cells abolishes the vasodilation to acetylcholine (Ach) but not sodium nitroprusside (SNP). Differential properties of endothelial cells in the series-arranged arterioles to vasodilator responses have not been studied. In this study, the cheek pouch microcirculation from the golden syrian hamster anesthetized with sodium pentobarbital (6 mg/100 g body wt, ip) was prepared for intravital microscopy. Measurements of lumen diameters of small series-arranged arterioles (2nd- and 4th-order) were made before, during, and after topical microapplication of different doses of either Ach or SNP. After control measurements, a light-dye (L-D) technique utilizing sodium fluorescein (FITC-dextran(150K), 50 mg/100 g body wt, iv) and illuminating a discrete area of the arteriole with 490-nm-wavelength light for 3 (4th) or 10 (2nd) min was used to impair endothelial cell function without damaging vascular smooth muscle cells. Responses to vasoactive substances for both 4th-order (10-20 microns) and second-order (30-50 microns) arterioles were retested. Vasodilatory responses to 10(-7) M Ach and SNP also were tested with and without the presence of NG-monomethyl L-arginine (L-NMMA), an inhibitor of EDRF/NO formation. In the control state, Ach and SNP produced a focal, dose-dependent increase in diameter in all arterioles tested. Endothelial impairment by L-D treatment significantly suppressed the vasodilator response to Ach in 4th- but not 2nd-order arterioles, whereas the SNP response was not significantly affected. Consistent with these observations, L-NMMA treatment significantly attenuated Ach-induced vasodilation in 4th-order arterioles, but it had no effect on 2nd-order arterioles. These studies document further the role of the endothelium in local modulation of arteriolar diameter in response to acetylcholine and demonstrate a differential effect for this response in series-arranged microvessels. Thus, there may be a heterogeneous distribution of endothelial cell functions for modulating vasodilator activity in microvessels.

Acetylcholine↗

DRw11 haplotypes: continuum of DRB1 diversity augmented by unique DQ/DRw52 associations.

cDNA sequencing of the first domains of DRB1, DRB3, DQA1, and DQB1 alleles was used to examine the extent of diversity in American black individuals expressing several DRw11 haplotypes. In addition to previously described DRw11 alleles, DRB1*1102 and DRB1*1103, two new DRB1 alleles, DRB1*11012 and DRB1*11042, were identified which differ from previously described alleles at the nucleic acid but not at the protein level. Gene conversion-like events have likely generated the DRw11 microvariation resulting in the merging of DRw11 with the DRw13 allele family. The DRw11 alleles are associated with various DQ alleles: DQw1 (DQw5 and DQw6), DQw7, and a serologically undefined DQ allele. This undefined DQ molecule, comprised of a DQ alpha/beta combination encoded by a DQw7 alpha gene (DQA1*0301) and a DQw2 beta gene (DQB1*0201), was previously observed in some DR7 and DR9 haplotypes. DRw11 haplotype diversity is augmented by the association of one of the DRw11 alleles with the DRw52c allele in contrast to the more common DRw11, DRw52b association. The extensive diversity exhibited by the DRw11 and DRw13 family of haplotypes coupled with their high frequency in populations of African ancestry suggest that the DRw11/w13 allele family may be very old and/or that these haplotypes carry some selective advantage.

Amino Acid Sequence↗

Blocking type immunoglobulins in patients with nongoitrous primary hypothyroidism in area of iodine deficiency.

We have evaluated the role of circulating serum immunoglobulins (IgG) which inhibit the growth of thyroid in the etiology of thyroid atrophy in endemic cretinism. Twenty nongoitrous cretins (13 women and 7 men, age range: 9-33) were classified on the basis of clinical criteria for cretinism in China. They were born and living in an iodine deficient area, Xinjiang, northwest China. Antimicrosomal antibody titers were negative in all serum. Nine patients (seven women and two men; age range: 11-23) were biologically primary hypothyroid. Seven subjects were of a myxedematous form and two subjects were of a mixed form. We have studied thyroid-growth inhibiting immunoglobulin (TGII) activity that was measured as an inhibitory effect of 4 mg/ml IgG on TSH-induced [3H]-thymidine incorporation into the DNA of a rat thyroid follicular cell line, FRTL5 cells. Six (five women and one man) out of the nine patients with primary hypothyroidism (66.7 percent) had TGII. We also measured other growth-blocking IgG that inhibited [3H]-thymidine incorporation into DNA stimulated by insulin-like growth factor-I (IGF-I), a growth factor working through a cAMP-independent pathway. Five (three women and two men) out of nine patients (55.6 percent) with nongoitrous primary hypothyroidism had IGF-I-blocking IgG. These results indicate that TGII plays an important role in atrophy of the thyroid in spite of increased serum TSH concentrations, and IgG which inhibits thyroid growth stimulated by IGF-I also might play a role in thyroid atrophy in some endemic cretins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparative inhibitory and bactericidal activities of FCE 22101 against gram-positive cocci and anaerobes in vitro.

The inhibitory activity of penem FCE 22101 was compared with those of imipenem and other relevant antibiotics against over 500 clinical isolates of Gram-positive cocci and anaerobes. The relative bactericidal activities of FCE 22101 and imipenem were compared by a killing curve method. FCE 22101 showed good inhibitory activity against most aerobic Gram-positive cocci although generally less than imipenem. A substantial number of Staphylococcus aureus isolates (43%) were highly susceptible to imipenem (MIC less than 0.0015 mg/l); the mode MIC for FCE 22101 was 0.06 mg/l. Methicillin-resistant Staph. aureus (MRSA) were often slightly more susceptible to FCE 22101 than to imipenem. Streptococci were more susceptible to imipenem than to FCE 22101; mode MICs for group A streptococci were 0.003 and 0.03 mg/l and for enterococci 1 and 4 mg/l, respectively. The anaerobic organisms tested were equally susceptible to both FCE 22101 and imipenem. Imipenem and FCE 22101 showed similar bactericidal activity at a concentration equivalent to 4 x MIC. Fully susceptible staphylococci were killed rapidly by both compounds, whereas less susceptible isolates, especially MRSA, were killed slowly. Streptococci, other than Str. pneumoniae, were also killed relatively slowly. Bacteroides fragilis group organisms were rapidly killed by both FCE 22101 and imipenem.

Anti-Bacterial Agents↗

Doxorubicin cardiomyopathy in children with left-sided Wilms tumor.

Two children with Wilms tumor of the left kidney experienced severe anthracycline cardiomyopathy after irradiation to the tumor bed and conventional dosage of doxorubicin. The cardiomyopathy is attributed 1) to the fact that radiation fields for left Wilms tumor include the lower portion of the heart and 2) to the interaction of doxorubicin and irradiation on cardiac muscle. It is recommended that doxorubicin dosage be sharply restricted in children with Wilms tumor of the left kidney who receive postoperative irradiation.

Cardiomyopathies↗

Host defense against opportunist microorganisms following trauma. I. Studies to determine the association between changes in humoral components of host defense and septicemia in burned patients.

Total hemolytic complement (CH(50)), conversion of C3 by inulin, and immunochemical levels of Clq, C4, C2, C3, C5, factor B, C3b inactivator (KAF), and properdin were measured in the sera of 15 patients with severe thermal injury during nine weeks postburn. Five of the 15 patients had multiple episodes of septicemia as documented by positive blood cultures and clinical findings. Decrease in CH(50), Clq, C4, C2, C3, and C5 occurred prior to and during septic episodes in these patients. Although conversion of C3 by inulin was often reduced during septic episodes, levels of factor B and KAF were generally normal or elevated. In only one patient did consumption of complement occurring during septicemia decrease the opsonic capacity of the patient's sera for the patient's infecting microorganism, an isolate of E. coli; sera from the same patient opsonized her infecting strain of S. aureus normally. The microorganisms isolated from the other septic patients, which were opsonized normally by the patients' sera despite complement consumption, were also with one exception strains of Staphylococci. In the nonseptic burned patients, decrease in properdin and C3 conversion by inulin, and increase in C3, factor B and KAF were demonstrated as we have previously reported. The results indicate that the classical complement pathway was activated during septicemia in burned patients and that activation of this pathway occurred preferentially due to inhibition of the alternative pathway. In addition, the data show that complement consumption may reduce the opsonic capacity of a patient's sera for certain microorganisms and not for others.

Adolescent↗

Carcinogen activation by human liver enzymes in the Ames mutagenicity test.

Liver post-mitochondrial supernatants derived from 10 individuals were used as the source of metabolic activation for carcinogens in the Ames quantitative mutagenicity test using Salmonella typhimurium TA 100. The liver samples were obtained from brain-dead donors and autopsy cases. The ability of human enzymes to activate aromatic amines ranged from the undetectable to highly active for 2-acetylaminofluorene. None of the samples exhibited any ability to activate benzidine. A generally low activity was observed in the capability of human enzymes to activate the polynuclear aromatic hydrocarbons, 3-methylcholanthrene and benzo(a)pyrene. Most samples were positive for activating 4-nitrobiphenyl. However, the highest mutagenic activity in the presence of human enzymes was consistently observed for aflatoxin B1 and sterigmatocystin. These results indicated that (a) human enzyme systems, like rodent systems, are more effective in inducing mutagenic activity from mycotoxins than aromatic amines and polynuclear aromatic hydrocarbons, and (b) samples derived from different individuals exhibited considerable variation in the ability to activate carcinogens belonging to a same class of compound.

Adult↗

Production of a sporulation pigment by Streptomyces venezuelae.

Streptomyces venezuelae S13 produced a pH-indicating sporulation pigment on a glucose-salts-agar medium consisting of glucose, KNO(3), MgSO(4), and Na(2)HPO(4), pH 7. Pigmentation on this medium appeared to be closely associated with sporulation, which normally required 5 to 7 days at 30 C. The pigment was soluble in water as well as in a number of organic solvents. Butanol-extracted pigment exhibited absorption maxima at 430 and 520 nm at pH 3 and 12, respectively. Although many salts of organic acids and amino acids could replace glucose as the sole carbon source in basal salts-agar medium for growth and pigmentation, most sugars that were tested supported good growth but negligible pigmentation. Among the nitrogenous substances tested, KNO(3) was most desirable for pigmentation. The organism did not exhibit any specific requirements for divalent cations with respect to growth and pigmentation. In the absence of MgSO(4), however, glucose-salts-agar prepared by autoclaving all components together failed to support growth. The production of the sporulation pigment on glucose-salts-agar was comparable to that obtained on tomato paste-oatmeal-agar medium. Incorporation of partially purified pigment material into broth medium that did not normally support sporulation induced sporulation, and amino acid-salts-agar medium could induce vegetative mycelia to pigment when transferred from medium that did not support either pigmentation or sporulation.

Agar↗