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Biomedical subjects

R C Ma

Publications and source records attributed to R C Ma.

At least 19 recordsLinked to original sources

Risk factors for cataract in Chinese patients with type 2 diabetes: evidence for the influence of the aldose reductase gene.

There is evidence that the development of retinopathy in type 2 diabetes is associated with a microsatellite polymorphism at 5' of the aldose reductase gene. The study examined whether cataract was associated with clinical/metabolic factors and/or the microsatellite polymorphism using a cohort of consecutively recruited Hong Kong Chinese patients with type 2 diabetes (n=567). Amongst these patients, 157 (28%) had cataract. The patients with cataract were older in age and age at diagnosis and had longer diabetes duration than those without cataract (all at p<0.01). They also had higher systolic blood pressure (p<0.01), HbA1c (p<0.05) and fasting plasma glucose levels (p<0.01; all with adjustment for the significance). Moreover, we found that the patients with cataract over-presented the microsatellite allele Z (23 vs. 30%, p<0.01) and its genotypes (Z,Z+Z,non-Z; 38 vs. 50%, p<0.01), but under-presented the allele Z-4 (8.3 vs 4.8%, p<0.05) and its genotypes (Z-4, Z-4+Z-4,non-Z-4; 16 vs. 10%, p<0.05). Using multiple logistic regression analysis (R2=0.25, p<0.01), we found that the presence of cataract was correlated positively with age, but inversely with the presence of allele Z-4. In conclusion, our data indicate that the occurrence of cataract is common in the Chinese type 2 diabetes population, with age and the aldose reductase gene as important determinants.

Aged↗

The RNase PD2 gene of almond (Prunus dulcis) represents an evolutionarily distinct class of S-like RNase genes.

A cDNA for an S-like RNase (RNase PD2) has been isolated from a pistil cDNA library of Prunus dulcis cv. Ferragnés. The cDNA encodes an acidic protein of 226 amino acid residues with a molecular weight of 25 kDa. A potential N-glycosylation site is present at the N-terminus in RNase PD2. A signal peptide of 23 amino acid residues and a transmembrane domain are predicted. The two active-site histidines present in enzymes of the T2/S RNase superfamily were detected in RNase PD2. Its amino acid sequence shows 71.2% similarity to RNSI of Arabidopsis and RNase T2 of chickpea, respectively. Northern blotting and RT-PCR analyses indicate that PD2 is expressed predominantly in petals, pistils of open flowers and leaves of the almond tree. Analyses of shoots cultured in vitro suggested that the expression of RNase PD2 is associated with phosphate starvation. Southern analysis detected two sequences related to RNase PD2 in the P. dulcis genome. RFLP analysis showed that S-like RNase genes are polymorphic in different almond cultivars. The PD2 gene sequence was amplified by PCR and two introns were shown to interrupt the coding region. Based on sequence analysis, we have defined three classes of S-like RNase genes, with the PD2 RNase gene representing a distinct class. The significance of the structural divergence of S-like RNase genes is further discussed.

Amino Acid Sequence↗

Glycaemic control in type 2 diabetes: the impact of body weight, beta-cell function and patient education.

We examined the determinants of glycaemic control in a consecutive cohort of 562 newly-referred Chinese type 2 diabetic patients (57% women) during a 12-month period. All patients underwent a structured assessment with documentation of clinical and biochemical characteristics. Pancreatic beta-cell function was assessed by fasting plasma C-peptide concentration. Insulin deficiency was defined as fasting plasma C-peptide <0.2 pmol/ml. Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA) based on a product of fasting plasma glucose and insulin concentrations. Treatment was considered appropriate when insulin-deficient patients were treated with insulin and non-insulin-deficient patients were treated with oral agents or diet. Mean (+/-SD) age was 54.3+/-13.8 years (range 17-87 years) and disease duration was 5.0+/-5.9 years. At the time of referral, 70.5% (n=396) were on drug therapy (9% on insulin and 62.8% on oral agents), 20.6% (n=116) were on diet and 9% (n=50) had not received any form of treatment. The mean HbA(lc) was 8.4+/-2.3%. The geometric mean (x// antilog SD) of IR was 4.62x//2.51 (range 0. 63-162.7) and correlated only with waist : hip ratio (WHR, p=0.008). The geometric mean of plasma C peptide was 0.47x//2.89 nmol/l and correlated with BMI (p<0.001). Glycated haemoglobin was correlated positively with age (p=0.013), disease duration (p<0.001), IR (p<0. 001) and negatively with BMI (p<0.001). Glycated haemoglobin was lower in patients who had seen a dietitian (7.9% vs. 8.7%, p<0.001) or diabetes nurse (7.8% vs. 8.7%, p<0.001) or who performed self blood glucose monitoring (7.9% vs. 8.6%, p=0.001) and higher among smokers (8.9% vs. 8.2%, p=0.003). Compared to insulin-deficient patients (n=118), non-insulin-deficient patients (n=413) had features resembling that of the Metabolic Syndrome with increased WHR (p=0.005), blood pressure (p<0.001), BMI (p=0.001) and were older (p=0.04). Amongst the insulin-deficient patients, 27% were treated with oral agents or diet. Patients receiving appropriate therapy (n=362) had a lower HbA(lc) than those treated inappropriately (n=173) (8.2% vs. 8.7%, p=0.02). On multivariate analysis, short disease duration (p<0.001), low IR (p<0.001), high BMI (p=0.001), diabetes education (p<0.001), lack of smoking (p=0. 014) and choice of appropriate treatment (p=0.009) were the independent determinants of good glycaemic control.

Adolescent↗

Diabetes in Hong Kong Chinese: evidence for familial clustering and parental effects.

OBJECTIVE: To investigate transmission patterns of diabetes and their relationships with clinical characteristics in Hong Kong Chinese patients with late-onset (age > or =35 years) type 2 diabetes. RESEARCH DESIGN AND METHODS: This study involved 2,310 patients consecutively selected from a hospital clinic-based diabetes registry. These patients all reported the diabetes status of their parents as well as siblings. RESULTS: Approximately 36% of the 2,310 patients reported at least 1 affected parent or sibling (25 and 21% reported at least 1 diabetic parent and sibling, respectively). These patients, irrespective of their sex, were more likely to have a diabetic mother than a diabetic father (17 vs. 13% of the male patients and 18 vs. 9% of the female patients, P<0.01). The male patients were more likely than the female patients to have a diabetic father (13 vs. 9%, P<0.01). The female patients with a diabetic mother were found to have higher levels of plasma total cholesterol compared with the female patients with a diabetic father in multiple comparisons with adjustment for significance (5.56+/-1.30 vs. 5.09+/-0.95 mmol/l, P<0.05). In 2-group comparisons, there was also evidence that the male patients with a diabetic father had higher BMI values than the male patients with a diabetic mother (25.9+/-3.5 vs. 25.0+/-3.5 kg/m2, P<0.05). CONCLUSIONS: We found familial clustering of diabetes in the Hong Kong Chinese population as well as a significant maternal influence and a male sex-specific paternal effect. We suggest that both maternal and paternal factors may be implicated in the development of type 2 diabetes in the Chinese population.

Adult↗

Systemic Weber-Christian disease complicated by partial transverse myelopathy.

Weber-Christian disease is an inflammatory disorder of fatty tissue which usually presents with raised red tender nodules in the skin. Although there may be additional systemic upset, there are very few reports of neurological features associated with this condition. We report a patient with biopsy-confirmed systemic Weber-Christian disease in whom a transient partial myelopathy, of probable inflammatory origin, was the most prominent feature. Based on recent reports of the effects of immune mediators on neuronal function, a possible pathogenetic explanation for this syndrome is suggested.

Adult↗

5-HT1P receptor-mediated slow depolarization in neurons of guinea pig inferior mesenteric ganglion.

AIM: To study the effects of several 5-hydroxytryptamine (5-HT) receptor subtype antagonists on 5-HT-induced depolarization and the effects of 5-HT1P receptor agonist on the membrane potential in the neurons of guinea pig inferior mesenteric ganglion (IMG). METHODS: Intracellular recordings were made from neurons of the isolated guinea pig IMG. RESULTS: Cyproheptadine (5-HT1/2 antagonist 10 mumol.L-1, n = 7) and BRL 24924 (5-HT1P antagonist 10 mumol.L-1, n = 19) reversibly suppressed 5-HT slow response; pressure ejection of MCPP (5-HT1P agonist 10 mmol.L-1) induced a slow depolarization in most of 5-HT sensitive neurons (10/14). CONCLUSION: 5-HT-induced slow depolarization is mediated by 5-HT1P receptor.

Animals↗

Substance P- and 5-hydroxytryptamine-mediated depolarization in sympathetic ganglion neurons.

By means of intracellular recordings from sympathetic ganglion in vitro, the present study was to investigate whether the receptors of substance P (SP) and 5-hydroxytryptamine (5-HT) exist in the same neuron or separately in different neurons of guinea pig celiac ganglion (CG) and inferior mesenteric ganglion (IMG) and whether there are some interactions between the two transmitters. Of the 133 neurons of CG, 66 (49.6%) responded to both SP and 5-HT, 40 (30.1%) only to SP or 5-HT, 27 (20.3%) insensitive to both. The corresponding numbers of the corresponding groups of neurons of the 129 IMG neurons are 47 (36.4%), 65 (50.4%) and 17 (13.2%). Continuous superfusion of IMG with 5-HT did not affect SP depolarization, while continuous superfusion of IMG with SP did not affect 5-HT depolarization. The results indicate that SP receptor and 5-HT receptor may exist in the same neuron, and neither affects each other.

Animals↗

Cholinergic transmission in pancreatic ganglia of the cat.

Although there is considerable evidence indicating the existence of important cholinergic neural regulation of pancreatic function, very little is known about the action of acetylcholine on pancreatic ganglion neurons. The present study was undertaken to determine the effect of pressure microejection of acetylcholine and muscarine on ganglion cell excitability of the cat pancreas. Recordings were made in vitro from ganglion neurons located in the head region of the pancreas. Acetylcholine evoked a fast- and a slow-developing membrane depolarization in the majority of neurons tested. A decrease in membrane input resistance accompanied the fast depolarizing response, whereas an increase in input resistance accompanied the slow depolarizing response. The fast response was mimicked by 1,1-dimethyl-4-phenylpiperazinium iodide and nicotine and antagonized by hexamethonium. The slow depolarizing response was mimicked by muscarine and antagonized by atropine and pirenzepine. The dependence of the slow depolarization on extracellular K+ and the distinct voltage dependence of the slow depolarization suggest that activation of muscarinic receptors was due to inactivation of IM. The slow excitatory postsynaptic potential and associated increase in excitability evoked by repetitive nerve stimulation was partially cholinergic dependent in the majority of neurons tested. It was concluded that cholinergic transmission in cat pancreatic ganglia involves nicotinic and M1 receptors that mediate fast and slow synaptic transmission, respectively, and that activation of M1 receptors modifies the output firing frequency.

Acetylcholine↗

[Receptors of monoamine in sympathetic preganglionic neurons of neonatal rat spinal cord in vitro].

By means of intracellular recordings from spinal cord slices of neonatal rats in vitro, the effects of 5-hydroxytryptamine (5-HT), nor-adrenaline (NA) and adrenaline (AD) on membrane potential in sympathetic preganglionic neurons (SPN) were observed, in order to clarify whether these neuron contain a single type of the monoamine receptor or in combination with more than one type of receptors. The results showed that: (1) 5-HT, NA and AD induced membrane depolarization respectively in 57.1% (16/28), 60% (15/25) and 52.4% (11/21) of SPN. (2) According to the reactions of SPN to the three monoamines, several subtypes of SPN could be divided: those sensitive to all the three monoamines (3/19), those sensitive to two of them (9/19), those only sensitive to one type of monoamines (4/19) and those insensitive at all (3/19). The significance of coexistence of more than one type of the three monoamines in a single neuron remains to be elucidated.

Animals↗

Modulation by opioid peptides of mechanosensory pathways supplying the guinea-pig inferior mesenteric ganglion.

1. Radioimmunological techniques were used in isolated guinea-pig inferior mesenteric ganglion (IMG)-colon preparations to determine whether opioid peptides and neurotensin8-13 (NT8-13), the C-terminal region of NT1-13 recognized by neurotensin receptors, modulate distension-induced release of substance P (SP)- and vasoactive intestinal polypeptide (VIP)-like immunoreactive (LI) material. 2. Colonic distension significantly increased the amount of SP- and VIP-LI material released in the ganglionic superfusate. A low-Ca2+ (0.1 mM), high-Mg2+ (15 mM) solution blocked their release. 3. In vivo capsaicin pretreatment abolished release of SP-LI material during colonic distension but had no significant effect on distension-induced release of VIP-LI material. 4. The addition of [Leu5]enkephalin, [Met5]enkephalin, PL017 (a mu-receptor agonist) and DPDPE (a delta-receptor agonist) to the ganglion side of a two-compartment chamber blocked distension-induced release of SP-LI material. The addition of naloxone and ICI-174,864 (a delta-receptor antagonist) to the ganglion compartment reversed the inhibitory effect of the mu- and delta-receptor agonists. 5. Addition of [Leu5]enkephalin and [Met5]enkephalin to the ganglion compartment had no significant effect on release of VIP-LI material during colonic distension. 6. Addition of NT8-13 to the ganglion compartment significantly increased in the amount of SP-LI material released during colonic distension but had no affect on distension-induced release of VIP-LI material. 7. The results suggest the hypothesis that under in vivo conditions, enkephalinergic nerves decrease and neurotensinergic nerves increase the release of SP from peripheral branches of primary afferent sensory nerves.

Animals↗

5-Hydroxytryptamine depolarizes neurons of cat pancreatic ganglia.

Pancreatic ganglia contain 5-hydroxytryptamine (5-HT)-immunoreactive axons, some of which are extensions of myenteric neurons located in the pyloric antrum and proximal duodenum. The present study investigated the effect of 5-HT on the membrane potential of cat pancreatic ganglion neurons by means of intracellular recordings in vitro. Pressure application of 5-HT evoked a fast depolarization in 29 of 147 neurons and a slow depolarization in 89 of 147 neurons. A biphasic response was observed in 10 of 108 neurons. The 5-HT-induced slow depolarizing response was not altered in a low Ca2+ (0.1 mM), high Mg2+ (15 mM) solution nor by hexamethonium (10(-4) M) or atropine (10(-6) M). The fast depolarizing response was associated with a decrease of membrane input resistance (-17.2%). The slow depolarizing response was associated with either a decrease (-19.6%) in 24, an increase (+25.0%) in 20, or without a detectable change of membrane input resistance in 10 out of 54 neurons tested. Conditioning hyperpolarization increased the amplitude of both fast and slow depolarizing responses. A low Na+ (68.5 mM) solution and a high K+ (23.5 mM) solution significantly reduced the amplitude of the slow depolarizing response. A low Cl- (9.6 mM) solution had no significant effect on the slow depolarization. The 5-HT3 receptor antagonist MDL 72222 (Bemesetron) blocked the 5-HT-evoked fast depolarizing response. BRL 24924 (Renzapride) and 5 HT-DP, antagonists for the putative 5-HT1P receptor, blocked the slow depolarizing response. The 5-HT3 receptor agonist 2-methyl-5-HT evoked a fast depolarizing response and MCPP, an agonist for the putative 5-HT1P receptor, evoked a slow depolarizing response. Spiperone (a 5-HT1A receptor antagonist) and mianserin (a 5-HT2 receptor antagonist) had no effect on either depolarizing response to 5-HT. The results show that pancreatic ganglion neurons responded to 5-HT with fast and slow depolarizing responses. The data suggest that these responses were mediated by the 5-HT3 receptor and the putative 5-HT1P receptor, respectively.

Animals↗

Release of calcitonin gene-related peptide in guinea pig inferior mesenteric ganglion.

Neurons of the guinea pig IMG are surrounded by nerve fibers containing CGRP-like immunoreactivity (LI). The purpose of this study was to determine whether colonic distension releases CGRP-LI in the IMG and whether opioid peptides and neurotensin(8-13) [NT(8-13)] modulate its release. Colonic distension released CGRP-LI. Methionine-enkephalin acted through mu and/or delta receptors to block release. NT(8-13) had no effect on release of CGRP-LI. Capsaicin pretreatment reduced the content of CGRP-LI in the IMG by 37%. Colonic distension did not release CGRP-LI from capsaicin-insensitive fibers. The data suggest that colonic distension releases CGRP-LI material from capsaicin-sensitive nerves and that enkephalins modulate release of CGRP-LI.

Afferent Pathways↗

Cholecystokinin depolarizes neurons of cat pancreatic ganglion.

The effect of cholecystokinin octapeptide (CCK-8) on membrane potential and conductance of cat pancreatic ganglion neurons was studied in vitro by means of intracellular microelectrode recording methods. Microejection of S-CCK-8 and NS-CCK-8 evoked, by direct action, a slow, reversible membrane depolarization. The majority of neurons tested were more sensitive to S-CCK-8. The depolarizing response to S-CCK-8 and NS-CCK-8 was accompanied in different neurons by a variable change in membrane permeability to Na+ and/or K+. The effects of S-CCK-8 and NS-CCK-8 were mediated by the CCKB receptor. The results suggest that S-CCK-8 and NS-CCK-8 increase the excitability of pancreatic ganglion neurons by acting on postsynaptic CCKB receptors.

Animals↗

Facilitating effect of CCK on nicotinic neurotransmission in cat pancreatic ganglion.

Previous studies have demonstrated the presence of cholecystokinin (CCK)-like peptides in nerve terminals surrounding ganglion neurons of the cat pancreas. The present study was undertaken to determine the effect of cholecystokinin octapeptide (CCK-8) on ganglionic transmission. Recordings were made intracellularly in vitro from ganglion neurons in isolated pieces of the pancreas. Sulfated CCK-8 (S-CCK-8) and nonsulfated CCK-8 initiated or increased ongoing fast excitatory postsynaptic potential (fEPSP) activity, an effect antagonized by hexamethonium. Superfusion of S-CCK-8 in concentrations ranging from 10(-11) to 10(-8) M significantly augmented the amplitude of nerve-evoked subthreshold fEPSPs without a significant change in either membrane potential or membrane input resistance. S-CCK-8 (10(-8)M) also increased the quantal content and quantal size of nerve-evoked fEPSPs and increased the response to exogenously applied acetylcholine (ACh). Concentrations of S-CCK-8 higher than 10(-8)M caused depolarization and an increase in membrane input resistance, an effect unaltered by a low-Ca+, high-Mg2+ solution. It was concluded that S-CCK-8 potentiated nicotinic transmission by facilitating release of ACh from preganglionic nerve terminals and by increasing the postsynaptic membrane sensitivity to ACh.

Acetylcholine↗

[The relationship of late slow excitatory potential with 5-hydroxytryptamine and substance P in the guinea-pig celiac ganglion].

The work was carried out to investigate the relationship of non-cholinergic late slow excitatory potential (LS-EPSP) with 5-hydroxytryptamine (5-HT) and substance P (SP) in the neurons of the guinea pig celiac ganglion (CG) using intracellular electrodes in vitro. During repetitive stimulation of the splanchnic nerve (SN), LS-EPSP following a series of action potentials could be recorded in 161 out of 206 neurons (78.2%); Application of 5-HT and SP by superfusion or pressure ejection induced 5-HT depolarization in 102 out of 149 neurons (68.5%) and SP depolarization in 98 out of 188 neurons (52.1%), respectively; Most neurons, from which LS-EPSP could be recorded during stimulation of SN, were sensitive to 5-HT (73/88, 83.0%) and SP (68/114, 59.7%). However, only a small number of neurons not showing LS-EPSP during stimulation of SN were sensitive to 5-HT (10/26, 38.5%, P < 0.0001) and SP (11/36, 30.6%, P < 0.01). The results support the viewpoint that both 5-HT and SP are involved in the formation of LS-EPSP as transmitters; In addition, both effects of 5-HT and SP were examined in 133 neurons. There were 66 of these neurons (49.6%) to be sensitive to both 5-HT and SP, suggesting that there may be some functional relations between 5-HT and SP in the neurons of guinea pig CG.

Animals↗

Direct and indirect mechanosensory pathways from the colon to the inferior mesenteric ganglion.

The aims of these experiments were to determine in vitro whether colonic distension releases acetylcholine, vasoactive intestinal polypeptide (VIP), and substance P in the guinea pig inferior mesenteric ganglia (IMG) and whether cholinergic and peptidergic mechanosensory nerves projecting from the colon to the IMG receive cholinergic input from other enteric neurons. Colonic distension significantly increased the release of [3H]-acetylcholine, VIP-like immunoreactivity, and substance P-like immunoreactivity in the IMG. Nicotinic receptor blockade in the colon diminished the increase in [3H]acetylcholine release, abolished the increase in VIP-like immunoreactivity release during distension, but had no effect on the release of substance P-like immunoreactivity. Nicotinic receptor blockade in the colon also decreased fast mechanosensory input and significantly reduced by 54% the slow excitatory postsynaptic potential amplitude evoked by colonic distension. The data suggest that enteric cholinergic and VIP mechanosensory neurons that project from the colon to sympathetic neurons in the IMG receive peripheral cholinergic input from other enteric neurons. There was no evidence for enteric cholinergic input to the mechanosensory substance P pathway.

Acetylcholine↗

Effect of nifedipine on neurons of guinea pig celiac ganglion.

The effect of nifedipine on electrophysiological membrane properties and nicotinic neurotransmission of guinea pig celiac ganglion neurons was studied using intracellular recordings in vitro. Nifedipine in concentrations of 0.1-10 microM did not affect membrane potential, membrane input resistance or the amplitude and duration of action potentials induced by intracellular current injection. Higher doses of nifedipine (0.1-1 mM) significantly reduced the amplitude and extended the duration of action potentials induced by intracellular current injection. Superfusion of the ganglia with nifedipine in concentrations of 0.1-10 microM significantly inhibited nicotinic fast excitatory postsynaptic potentials (f-EPSPs) and orthodromic action potentials evoked by nerve stimulation. This depressant effect of nifedipine on synaptic transmission was eliminated with high Ca2+ (12.5 mM). Nifedipine (10 microM) did not affect the postsynaptic effect of exogenous acetylcholine (ACh), but significantly reduced the quantal content but not the quantal size of evoked f-EPSPs in a low Ca2+ (0.5 mM), high Mg2+ (5.5 mM) Krebs solution. Nifedipine in concentration of 10 microM did not affect afterspike hyperpolarization (AH) and post-tetanic hyperpolarization (PTH), which have been recognized to be generated mainly by an increase of calcium-dependent potassium conductance. Higher doses of nifedipine (0.1-1 mM) significantly depressed AH and PTH. These experimental results suggest that nifedipine in concentrations of 0.1-10 microM exerts an inhibitory effect on nicotinic neurotransmission without affecting the membrane properties of the guinea pig celiac ganglion neurons. This inhibitory effect of nifedipine on synaptic transmission may result from blocking L-type calcium channels and reducing the quantal release of ACh from the presynaptic nerve terminals.

Animals↗

[Serotonin mediated synaptic transmission of inferior mesenteric ganglion of the guinea pig].

By means of intracellular recording technique, it was observed that: (1) Application of serotonin (5-HT) caused in a portion of the neurons of the guinea pig inferior mesenteric ganglia (IMG) a slow depolarization similar to non-cholinergic late slow excitatory postsynaptic potential (ls-EPSP). (2) Prolonged superfusion of 5-HT markedly suppressed the ls-EPSP in 5-HT sensitive neurons. (3) The ls-EPSP elicited in 5-HT sensitive neurons as well as the 5-HT depolarization could be enhanced by fluoxetine 5-HT reuptake inhibitor; In contrast, the ls-EPSP of 5-HT insensitive neurons was not appreciably changed by this drug. (4) Pretreating the guinea pigs with para-chlorophenylalanine (PCPA), a 5-HT biosynthesis inhibitor, markedly reduced the occurrence rate and amplitude of ls-EPSP. These results indicate that ls-EPSP of the guinea pig IMG is possibly mediated by several transmitters including 5-HT.

Animals↗