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Biomedical subjects

J Tang

Publications and source records attributed to J Tang.

At least 343 records · Page 19Linked to original sources

NIDDM is associated with loss of pancreatic beta-cell L-type Ca2+ channel activity.

Development of non-insulin-dependent diabetes mellitus (NIDDM) is associated with defects in glucose-stimulated insulin secretion. We have investigated Zucker diabetic fatty rats (ZDF), an animal model of NIDDM, and found that, compared with control islets, the expression of mRNA encoding C- and D-isoforms of alpha 1-subunits of beta-cell L-type voltage-dependent Ca2+ channels (VDCC) was significantly reduced in islets isolated from ZDF rats. This correlated with a substantial reduction of L-type Ca2+ currents (ICa) in ZDF beta-cells. Intracellular Ca2+ concentration responses in ZDF islets after glucose, KCI, or BAY K 8644 stimulation were markedly attenuated, whereas responses evoked by carbachol were unimpaired, consistent with a specific decrease in ICa in the diabetic islets. This reduction was accompanied by loss of pulsatile insulin secretion from ZDF islets treated with oscillatory increases of external glucose concentration. Our findings suggest that the attenuation of ICa in diabetic islets may contribute to the abnormal glucose-dependent insulin secretory responses associated with NIDDM and indicate that this defect is caused by decreased expression of genes encoding beta-cell VDCC alpha 1-subunits.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Preservation of insulin secretory responses to P2 purinoceptor agonists in Zucker diabetic fatty rats.

The role of P2 purinoceptor agonists in regulatory insulin secretion in Zucker diabetic fatty (ZDF) rats was studied using the isolated perfused pancreas and intracellular Ca2+ concentration ([Ca2+]i) microfluorimetry. The relative potency of different purinoceptor agonists to stimulate the insulin secretory process was consistent with the conclusion that responses in [Ca2+]i and insulin secretion are mediated by the P2y subtype of purinoceptors. Additional studies using specific antagonists of the Ca2+ signaling pathway indicated that activation of P2y purinoceptor releases Ca2+ from intracellular stores and promotes Ca2+ entry through voltage-independent rather than voltage-dependent Ca2+ channels on the beta-cell membrane. Perfused pancreas and isolated islets from ZDF rats demonstrated markedly reduced or absent insulin secretion and [Ca2+]i responses to glucose and KCl. In contrast, responses to P2y purinoceptor agonists were normal, indicating that the secretion coupling pathway activated by these agonists is preserved in glucose-unresponsive islets from diabetic animals. These observations raise the possibility that the purinoceptor pathway may play an important role in regulating insulin secretion in hyperinsulinemic non-insulin-dependent diabetes mellitus.

Adenosine↗

Low mitochondrial glycerol phosphate dehydrogenase and pyruvate carboxylase in pancreatic islets of Zucker diabetic fatty rats.

The enzyme activities of mitochondrial glycerol phosphate dehydrogenase (mGPD) (EC 1.1.99.5) and pyruvate carboxylase (PC) (EC 6.4.1.1) have been reported to be low in the pancreatic islet of several rodent models of NIDDM. The present study was undertaken to discern whether mGPD is abnormal in the Zucker diabetic fatty (ZDF) rat (ZDF/Gmi-fa/fa), an animal model of NIDDM in which insulin secretion is unable to counteract the insulin resistance associated with the obesity that characterizes this model. Experiments were performed in prediabetic 6-week-old ZDF rats in comparison with 12-week-old overtly hyperglycemic animals and, as controls, Zucker lean (ZL) rats (ZDF/Gmi-+/fa or -+/+) and Wistar rats (+/+) of the same ages. The enzyme activity of mGPD was 32 and 18% of normal in islets of 6- and 12-week-old ZDF rats, respectively (P < 0.001 by analysis of variance). The activity of PC, which like mGPD is relatively abundant in the pancreatic islet, was 17 and 10% of normal in the islets of 6- and 12-week-old ZDF rats, respectively (P < 0.001). The activity of mGPD was normal in islets from ZL rats. However, PC activity was slightly lower in islets of 6- (51% of normal, P = 0.007) and 12-week-old (67% of normal, P = 0.01) ZL rats. The amounts of mGPD protein, as judged from Western analysis, and of PC protein, as judged from probing transblots with streptavidin that binds to biotin-containing enzymes, roughly correlated with the enzyme activities. This indicates that the decreased enzyme activities are caused by the decreased net synthesis of these enzymes rather than by the decreased activity of a normal amount of enzyme. The enzyme activity of succinate dehydrogenase, a control for mGPD, was normal in the ZL and ZDF rats. An incidental finding of the current study was the discovery of beta-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase in the islet. Levels of these enzymes were also normal. Although reductions in mGPD and PC may contribute to the abnormal insulin secretion present in overt diabetes, they are modest compared with the severe reductions seen in inherited inborn errors of metabolism. Because of this and because more than a single enzyme is affected and the enzymes in the islet are diminished in more than one rodent model of NIDDM, these reductions are unlikely to represent the primary genetic defect in the ZDF rat. Since ZDF rats are euglycemic at 6 weeks of age and ZL animals are euglycemic throughout life and since these animals demonstrate low enzyme activities, this evidence suggests that it is not hyperglycemia but rather some other component of the diabetic syndrome that is responsible for the reductions in these enzymes.

Aging↗

[Surgical treatment of primary mediastinal tumor: a report of 90 cases].

In the past 22 years 90 cases of pathologically confirmed primary mediastinal tumors (PMT) were surgically treated. Of these 90 cases, there were 38 thymomas (42.3%), 19 teratoblastomas (21.2%), 9 neurofibromas (10.0%) and 24 others (26.5%). Radical excision was performed in 70 (77.8%), palliative excision in 6 (6.7%), exploratory thoracotomy in 12 (13.3%). Postoperative death occurred in 2 (2.2%). No relapse was reported in patients who had received radical excision during the follow-up period of 3 months to 13 years. Besides careful history taking and physical examination, X-ray examinations of the chest, particularly CT scan were valuable in the diagnosis and differential diagnosis of PMT. Difficulties in diagnosis were due to unusual pathological changes and clinical manifestations. Due precautionary measures should be taken to avoid injury to the heart, major blood vessels and the spinal cord. Cord injury was the consequence of direct operative trauma, compression due to intraspinal hemorrhage, and/or operative interruption of blood supply.

Adolescent↗

Delisting of drugs in Ontario. How attitudes and prescribing strategies of family physicians in the Kingston area changed.

OBJECTIVE: To assess how attitudes and prescribing strategies of family physicians changed when drugs were delisted from the Ontario Drug Benefit formulary. DESIGN: Mailed, self-administered survey. SETTING: Family physicians' offices in Ontario. PARTICIPANTS: All family physicians practising in the Kingston, Frontenac, Lennox, and Addington Health District. MAIN OUTCOME MEASURES: Physicians were presented with six vignettes involving patients receiving a delisted drug. The choices were to recommend the patient pay for the medication, to substitute a drug still listed on the formulary, to make a special request that the medication be covered for this patient, or to offer another option. As well, the physicians were asked to indicate, on a 5-point Likert scale, their opinions regarding the effect of delisting on themselves and their patients. RESULTS: Physicians were most likely to change to a medication that was still on the formulary. Patient sex and ability to pay were factors in physicians' decisions. Physicians believe that the delistings are not likely to have adversely affected patients' health, that noncompliance is a problem because many once-daily formulations have been removed, that suitable alternatives are not always available, and that physicians should have been consulted more before the changes were made. CONCLUSIONS: Physicians usually substitute listed medications for medications that have been delisted. This is especially true for female patients and patients who are unable to pay.

Adult↗

Investigation on inhibition of biological effects of endothelin.

The effects of a series of substances on the biological function of endothelin (ET) are reported. The substances used are: synthetic inhibitors of endothelium derived relaxing factors (EDRFs), inhibitor of big-endothelin converting enzyme phosphoramidon, antiserum of endothelin, antagonists of endothelin A receptor BQ123 and JKC301, and two Chinese anti-snake venom herb medicines Lobelia radicans Thumb and Taris polyphylla Smith var. chinensis (Franch) Hara. The results showed that inhibiting the production of nitric oxide (NO) could stimulate ET release from vascular endothelium, elevate plasma ET and increase blood pressure. These changes could be reversed by L-arginine (L-Arg), the substrate of nitric oxide synthase (NOS). The amount of ET released by arterial endothelium could be increased or inhibited by inhibiting or stimulating the synthesis of prostacyclin (PGI2). The plasma ET level and blood pressure in both SHR and WKY rats could be decreased by giving phosphoramidon (PhR). The above results indicate that the biological effects of ET could be antagonized by inhibiting the synthesis or release of ET, decreasing the level of plasma ET, blocking the binding of ET with its receptor and using some Chinese anti-snake venom herb medicines.

Animals↗

Characterization of yeast U1 snRNP A protein: identification of the N-terminal RNA binding domain (RBD) binding site and evidence that the C-terminal RBD functions in splicing.

The yeast U1A protein is a U1 snRNP-specific protein. Like its human counterpart (hU1A), it has two conserved RNA binding domains (RBDs). The N-terminal RBD is quite different from the human protein, and a binding site on yeast U1 snRNA is not readily apparent. The C-terminal RBD is of unknown function. Using in vivo dimethyl sulfate (DMS) protection of mutant strains, we defined a region in yeast U1 snRNA as the likely U1A N-terminal RBD binding site. This was confirmed by direct in vitro binding assays. The site is very different from its vertebrate counterpart, but its location within yeast U1 snRNA suggests a conserved structural relationship to other U1 snRNP components. Genetic studies and sensitive in vivo splicing measurements indicate that the yeast U1A C-terminal RBD also functions in pre-mRNA splicing. We propose that the N-terminal RBD serves to tether the splicing-relevant C-terminal RBD to the snRNP.

Alkylating Agents↗

The central distribution of adrenomedullin and its effects on blood pressure and heart rate in rats.

The present study was designed to make certain whether there exists adrenomedullin (ADM) in the rat central nervous system and evaluated the hemodynamic actions of intracerebroventricular administration (ICVA) of human ADM[13-52]. By immunohistochemistry (ABC method). We found that there was a discrete localization of ADM-positive immunoreactivity in the rat central system including cerebral cortex, paraventricular tissues, hypothalamus, cerebella cortex, mesencephalon and medulla oblongata. By reverse transcription-polymerase chain reaction (RT-PCR) analysis, rat ADM mRNA was found to be expressed in rat brain. These above results of immunohistochemistry and RT-PCR suggest that ADM exists in the rat brain. We also found that centrally administered ADM[13-52] in a dose of 0.4 to 3.2 nmol/kg provoked marked, prolonged and dose-dependent increases in mean arterial blood pressure (MABP) and heart rate (HR). To clarify the mechanisms of the hemodynamic changes induced by centrally administered ADM [13-52], the effect of centrally administered ADM[13-52] on renal sympathetic nerve activity (RSNA) was studied. The result showed that centrally administered ADM [13-52] (1.6 nmol/kg) provoked a marked increase in RSNA, therefore, the increases in MABP and HR induced by centrally administered ADM [13-52] might be due to the stimulation of central sympathetic mechanism. In addition, we also compared the relationship of activity and structure among the different fragments of ADM. In conclusion, ADM exists in the rat brain, and it may play an important role in the central control of cardiovascular system.

Adrenomedullin↗

[Mutation analysis of mitochondrial DNA of children with Rett syndrome].

OBJECTIVE: To identify whether mitochondrial DNA (mtDNA) mutation is involved in the pathogenesis of Rett syndrome (RS), we undertook a mutation analysis of the mtDNA genome. METHODS: mtDNA from 15 children with RS and 14 their mothers were analysed by using Southern hybridization, polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) and DNA direct sequencing. Total DNA was isolated from white blood cells. RESULTS: Southern hybridization with whole mtDNA probe revealed no large deletions in mtDNA. PCR amplification and SSCP analysis showed mutation(s) in the region 2650-3000 encoding 16SrRNA of mtDNA in 13 RS patients and 11 their mothers. DNA sequence analysis and mismatch PCR showed a point mutation (C-->T) at the position 2835 in 7 RS patients and 6 their mothers. The same mutation was not found in 30 normal controls. CONCLUSION: These data indicate that mtDNA may play a role in Rett syndrome.

Adult↗

[Two kinds of cytokine gene expression in umbilical cord blood of premature and mature neonates].

OBJECTIVE: To study the immunological function of premature and mature neonates. METHOD: By means of in situ hybridization technique, mRNA expression of interleukin-1 (IL-1) beta and IL-1r alpha in umbilical cord blood of 34 cases was analyzed. RESULTS: It showed that mRNA expression of IL-1 beta and IL-1r alpha were significantly lower in the group of preterm vaginal delivery resulting from premature rupture of membranes than that of preterm cesarean section with the indication of pregnancy induced hypertension and than that of full term delivery (P < 0.001). No significant difference was found between the latter 2 groups. CONCLUSIONS: It indicated that gene expression of IL-1 beta and IL-1r alpha probably related to the fetal maturity.

Adult↗

[Effects of bilateral lesions of ventrolateral orbital cortex on the rat tail flick reflex inhibition evoked by electroacupuncture].

This study found that bilateral electrolytic lesions of the ventrolateral orbital cortex (VLO) markedly reduced the inhibitory effects of high intensity electroacupuncture (EA) at "Zusanli" point on tail flick reflex in lightly anesthetized rats, but did not influence the inhibitory effects of low intensity EA stimulation. The results show that the VLO is involved in acupuncture analgesia produced by activation of small afferent fibers with high intensity electroacupunture. Results of this study provide further support for a hypothesis that spinal cord-Sm-VLO-PAG-spinal cord may constitute a negative feedback loop of nociceptive modulation. The analgesic effects produced by high intensity electroacupuncture may be mediated by this loop leading to depression of the nociceptive inputs at the spinal cord level.

Acupuncture Analgesia↗

[Responses of neurons in thalamic nucleus submedius to electrical stimulation of peroneal nerve and "zusanli" point in rats].

The experiments were performed on the anesthetized rats. Single unit was recorded extracellularlly from the thalamic nucleus submedius (Sm) with glass micropipettes. The responses of Sm neurons were examined to electrical stimulation of the peroneal nerve and "Zusanli" point. The results show that most (81%) of the neurons in Sm responded to electrical stimulation of the peroneal nerve with afferent C fiber excitation, and this response increased following increase of the stimulation intensity and pulse numbers. It was found that electrical stimulation of the "Zusanli" point could activate the Sm neuronal activities with higher intensity threshold compared to that of the peroneal nerve stimulation, and the response properties of Sm neurons to acupoint stimuli were similar to those to stimulation of peroneal nerve. These results provide support for the hypothesis that a negative feedback loop consisting of spinal cord-Sm-VLO-PAG-spinal cord responsible for nociceptive modulation is involved in acupuncture analgesia, especially in analgesia produced by electroacupuncture-evoked activation of the afferent C fibers.

Acupuncture Analgesia↗

[The influence of electroacupuncture with different frequencies on the discharges of neurons in rostral ventromedial medulla on rats].

The experiments were carried out on rats, anesthetized with urethan and paralyed with tubocuraine. Stainless steel needles were inserted into bilateral "Zusanli" points. The unit discharges of RVM neurons were recorded extracellalarly by microelectrode. The searching of nociceptive neurons and processing of data were operated automatically by a real time control system. The results were as follow: 1. The pain response of excitatory neurons could be inhibited by 2 Hz EA (n = 15/22, P < 0.01), the mean inhibition rate was 32.40%. 2. The inhibitory effects of 2 Hz were completely blocked by naloxone pretreated (n = 5/5, P < 0.01). 3. The pain response of excitatory neurons could be inhibited by 10 Hz EA(n = 10/13, P < 0.01), the mean inhibition rate was 49.06%. 4. The inhibitory effects of 10 Hz EA were partially blocked by naloxone pretreated (n = 5/5, P < 0.01). 5. Both 2 Hz and 10 Hz EA could enhance the spontaneous discharges of excitatory neurons in RVM, and the percentage of change in the frequency was 62.45% and 112.02% respectively. 6. Neither 2 Hz nor 10 Hz EA could obviously influence the spontaneous activity of inhibitory neurons in RVM. The results suggest that both 2 Hz and 10 Hz EA could activate excitatory neurons in RVM, which may suppress nociceptive transmission via opioid mechanism.

Acupuncture Analgesia↗

Chromosomal organisation of a repeated gene cluster expressed in mammalian stages of Leishmania.

The genomic organisation of a large Leishmania gene cluster, expressed predominantly in intracellular, infective parasite stages, has been determined. Using cosmid cloning, parasite DNA fingerprinting, partial digestion and mapping with 'end-specific' probes, the Lm cDNA2 gene array has been localised to a 55-kb ClaI fragment within the L. major genome. Six tandemly linked gene copies are transcribed to produce an abundant 6-kb transcript; the seventh and last copy of the cluster is truncated at its 3' end. It is likely that these genes encode one or more proteins specific to infective stages of the parasite life cycle.

Animals↗