The HLA-B gene and Hashimoto disease in Han Chinese children: a case-control and family-based study.

Hashimoto disease (HD) is an autoimmune thyroid disease resulting from complex interactions between genetic and environmental factors. The human leukocyte antigen (HLA) gene has been established to be involved in the susceptibility to HD. We aim to investigate the associations between HLA-B alleles and Han Chinese children with HD by both case-control and family-based studies. A total of 108 unrelated children with HD, 380 unrelated healthy controls, 58 trios of affected patients and their parents, and 75 trios of unaffected siblings and their parents were recruited. HLA-B genotyping was performed by polymerase chain reaction and detected with a sequence-specific oligonucleotide probes system. We found that B*46:01 allele (OR = 2.31, 95% CI 1.60-3.34, P(c) = 9.99 × 10(-5)) and carrier (OR = 3.28, 95% CI 2.10-5.11, P(c) = 1.35 × 10(-6)) were associated with HD risk. Transmission/disequilibrium test further confirmed an overtransmission of the B*46:01 (OR 2.55, 95% CI 1.36-6.10, P = 6.5 × 10(-3)). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA-B*46:01 confers susceptibility to HD in Han Chinese children. Further studies with larger children cohort are required to confirm the role of B*46:01 in the development of HD.

The HLA-DRB1 gene and Graves disease in Taiwanese children: a case-control and family-based study.

Graves disease (GD) is an autoimmune thyroid disease with a female preponderance and a wide range of ages at onset, and human leukocyte antigen (HLA) gene plays a primary role in the susceptibility to GD. We aim to investigate the associations between HLA-DRB1 alleles and Taiwanese children with GD by both case-control and family-based studies. A total of 241 unrelated children with GD, 539 healthy controls, 115 trios of affected patients and their parents, and 121 trios of unaffected siblings and their parents were recruited. HLA-DRB1 genotyping was performed by polymerase chain reaction and sequence-based typing assays. We found that DRB1*09:01 (OR=2.60, 95% CI 2.02-3.35, Pc=6.55×10(-13)) was associated with GD risk, while DRB1*12:02 (OR=0.32, 95% CI 0.20-0.53, Pc=4.55×10(-5)) was protective against GD. Transmission/disequilibrium test further confirmed an overtransmission of the DRB1*09:01 (OR 3.37, 95% CI 2.13-6.22, Pc=1.0×10(-5)) and an undertransmission of the DRB1*12:02 (OR 0.21, 95% CI 0.05-0.42, Pc=1.7×10(-3)). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA-DRB1*09:01 confers susceptibility to GD and DRB1*12:02 exerts protection against GD development in Taiwanese children.

N-methyl-D-aspartate receptor subunit composition in the rat trigeminal principal nucleus remains constant during postnatal development and following neonatal denervation.

N-methyl-D-aspartate receptors (NMDARs) play a major role in various forms of developmental and adult synaptic plasticity (Lopez de Armentia M, Sah P (2003) J Neurosci 23:6876-6883). Activity-dependent shifts in NR2 subunits of the NMDARs have been proposed to be the molecular basis of critical period plasticity. Several supporting examples have been reported; however it is not clear whether the relationship between NMDAR subunit changes and neural plasticity are correlative or causal, nor whether such a relationship is universal across all sensory pathways with developmental plasticity. In the present study, we used voltage-clamp recording techniques to investigate whether subunit composition of NMDARs changes during development and after neonatal denervation in the principal sensory nucleus (PrV) of the trigeminal nerve. Relative AMPA receptor contribution to synaptic transmission increased linearly by the second postnatal week in the normal PrV. Denervation by peripheral nerve damage did not alter this process. We took the weighted decay time constant (τw) of NMDAR-mediated EPSCs as an index for NMDAR subunit composition. The τw measurement and Western blot analysis revealed that NMDARs contained both NR2A and NR2B subunits. The NR2A/NR2B ratio did not change during postnatal development or after neonatal denervation. Thus, critical period plasticity-related pattern formation in the PrV does not depend on changes in subunit composition of NMDARs. The mechanism underlying developmental synaptic plasticity in the PrV differs from those in higher trigeminal centers and other brain structures.

Use of parenteral testosterone prior to hypospadias surgery.

Surgical correction of genital defects was formerly proposed when the size of the penis was sufficient to permit easy surgical repair. To enlarge penile size, temporary stimulation with testosterone or dihydrotestosterone cream has been used; however, the results were not only inconsistent, but absorption was also variable. We report our experience with parenteral testosterone as an adjunct to reconstructive genital surgery in 25 patients aged 6-18 months from July 1999 to December 2000, including 8 with penile hypospadias, 15 with penoscrotal hypospadias, and 2 with perineal hypospadias. Each had a penis that was significantly smaller than usual. Testosterone enanthate 25 mg was given i.m. once per month for a total of three doses before surgical repair. Penile length and glans circumference were measured before therapy and at operation. Side effects such as the development of pubic hair and acne were monitored. Bone age was checked 1 year later. An increase in penile length (from 19.8 +/- 2.4 mm to 23.8 +/- 2.0 mm) and glans circumference (from 27.4 +/- 1.4 mm to 37.84 +/- 2.6 mm) was apparent in all except 2 patients (P < 0.001 for both, paired t-test). Four patients had a significant increase in either penile length or glans circumference after the initial dose so that no further injections were required. No definite secondary effects were found. Preoperative parenteral testosterone therapy thus causes a significant increase in penile length and glans circumference without apparent side effects. We suggest that this therapy prior to microphallic hypospadias repair is appropriate.

Synaptic plasticity in the trigeminal principal nucleus during the period of barrelette formation and consolidation.

We examined whether the postsynaptic responses of cells in the principal sensory nucleus of the trigeminal nerve (PrV) are subject to long-term changes in synaptic strength, and if such changes were correlated the whisker-specific patterning during and just after the critical period for pattern formation. We used an in vitro brainstem preparation in which the trigeminal ganglion (TG) and PrV remained attached. By electrically activating TG afferents, we evoked large-amplitude extracellular field potentials. These responses were postsynaptic in origin and blocked by the glutamate antagonist, DNQX. At P1, a time when barrelettes are consolidating, high frequency stimulation of their afferents led to an immediate (<1 min) and long-lasting (> or =90 min) reduction (35%) in the amplitude of the evoked response. At P3-7, when the pattern of barrelettes have stabilized, the same form of tetanus led to an immediate and long-lasting increase (40%) in the amplitude of the response. Both forms of synaptic plasticity were mediated by the activation of L-type Ca(2+) channels. Application of the L-type channel blocker, nitrendipine, led to a complete blockade of any the tetanus induced changes. These associative processes may regulate the patterning and maintenance of whisker-specific patterns in the brainstem trigeminal nuclei.

The promoter region of the CTLA4 gene is associated with type 1 diabetes mellitus.

The CTLA4 (cytotoxic T lymphocyte associated antigen-4) gene encodes the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. C-T polymorphism is present at position -318 from the ATG start codon in the promoter region of the gene. We report a study on the polymorphism in 347 unrelated children with type 1 diabetes mellitus (DM) (age at diagnosis 7.2+/-3.8 years) and their 260 healthy siblings as controls. Genotype C/C conferred a risk of type 1 DM (RR = 2.02, 95% CI 1.32-3.10, pc = 0.0033). The gene frequency of the C allele was higher in patients (RR = 1.91, 95% CI 1.28-2.84, pc = 0.0026). The gene frequency and phenotype frequency of the T allele were negatively associated with type 1 DM (RR = 0.52, 95% CI 0.35-0.78, pc = 0.0026 and RR = 0.49, 95% CI 0.32-0.76, pc = 0.0022, respectively). The frequency of genotype C/T was lower in patients (RR = 0.50, 95% CI 0.32-0.78, pc = 0.0051). This study demonstrates that nucleotide -318 C-T polymorphism of the CTLA4 gene is associated with type 1 DM. The promoter allele -318 C confers a risk of type 1 DM but allele -318 T confers protection against this disease.

Neonatal deafferentation does not alter membrane properties of trigeminal nucleus principalis neurons.

In the brain stem trigeminal complex of rats and mice, presynaptic afferent arbors and postsynaptic target cells form discrete modules ("barrelettes"), the arrangement of which duplicates the patterned distribution of whiskers and sinus hairs on the ipsilateral snout. Within the barrelette region of the nucleus principalis of the trigeminal nerve (PrV), neurons participating in barrelettes and those with dendritic spans covering multiple barrelettes (interbarrelette neurons) can be identified by their morphological and electrophysiological characteristics as early as postnatal day 1. Barrelette cells have focal dendritic processes, are characterized by a transient K(+) conductance (I(A)), whereas interbarrelette cells with larger soma and extensive dendritic fields characteristically exhibit low-threshold T-type Ca(2+) spikes (LTS). In this study, we surveyed membrane properties of barrelette and interbarrelette neurons during and after consolidation of barrelettes in the PrV and effects of peripheral deafferentation on these properties. During postnatal development (PND1-13), there were no changes in the resting potential, composition of active conductances and Na(+) spikes of both barrelette and interbarrelette cells. The only notable changes were a decline in input resistance and a slight increase in the amplitude of LTS. The infraorbital (IO) branch of the trigeminal nerve provides the sole afferent input source to the whisker pad. IO nerve transection at birth abolishes barrelette formation as well as whisker-related neuronal patterns all the way to the neocortex. Surprisingly this procedure had no effect on membrane properties of PrV neurons. The results of the present study demonstrate that distinct membrane properties of barrelette and interbarrelette cells are maintained even in the absence of input from the whiskers during the critical period of pattern formation.

Polymorphism in the transmembrane region of the MICA gene and type 1 diabetes.

Although MHC class II genes have a stronger association with type 1 diabetes than MHC class I genes, studies have shown that MHC class I molecules play an independent role in the etiology of type 1 diabetes, and the existence of susceptibility genes within a segment of MHC between the HLA-B and TNF genes has been predicted, where MHC class I chain-related gene A (MICA) resides. MICA has a triplet repeat polymorphism in the transmembrane region consisting of five alleles. We analyzed this polymorphism in 162 unrelated children (82 boys) with type 1 diabetes (age at diagnosis 7.01 +/- 3.76 yr) and 154 randomly selected unrelated children (87 boys), age 2.81 +/- 2.12 yr. Phenotype frequency of allele A9 in children with type 1 diabetes was significantly higher than in controls (RR = 2.42, 95% CI = 1.52-3.85, p = 0.000162, pc = 0.00081). Gene frequency of allele A9 was also significantly higher in children with type 1 diabetes when compared with control children (RR = 2.73, 95% CI = 1.85-4.03, p = 2.62 x 10(-7), pc = 1.31 x 10(-6)). This study demonstrates that MICA allele A9 confers risk of type 1 diabetes.

Recurrent inhibitory circuitry in the deep layers of the rabbit superior colliculus.

1. Local inhibition in the deep layers of the superior colliculus plays a crucial role in sensorimotor integration. Using intracellular and extracellular recording techniques, we studied the organization of inhibitory circuits in the deep layers of the superior colliculus in anaesthetized rabbits. 2. We identified a new cell type in the deep superior colliculus that showed a characteristic burst response to stimulation of both the predorsal bundle and optic chiasm. The response had a jittering latency and failed to follow high frequency stimuli, indicating trans-synaptic (orthodromic) events. Moreover, the predorsal bundle stimulation-evoked orthodromic response could be made to collide with the response to a preceding stimulation of the optic chiasm, suggesting that burst-firing cells received excitatory inputs from the axonal collaterals of predorsal bundle-projecting cells. 3. Stimulation of the predorsal bundle could evoke an IPSP in predorsal bundle-projecting cells. The latency of the IPSP was 0.5-1.0 ms longer than the orthodromic response in burst-firing cells. Simultaneous recordings showed that the IPSP in predorsal bundle-projecting cells was preceded by a burst of extracellular spikes from burst-firing cells with short latency ( approximately 0.9 ms), indicating an inhibitory monosynaptic connection from burst-firing cells to predorsal bundle-projecting cells. 4. Burst-firing cells exhibited a prolonged depression after the predorsal bundle or optic chiasm stimulation due to an inhibitory postsynaptic potential. Latency analysis implies that burst-firing cells may form mutual inhibitory connections. 5. Together our results suggest that burst-firing cells and predorsal bundle-projecting cells form reciprocal excitatory and inhibitory connections and burst-firing cells may function as the recurrent inhibitory interneurons in the deep layers of the rabbit superior colliculus.

Association of CTLA4 gene A-G polymorphism with type 1 diabetes in Chinese children.

OBJECTIVE: The CTLA4 (cytotoxic T lymphocyte associated antigen-4) gene encodes the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. Thus it is a strong candidate gene for T cell-mediated autoimmune disease. There is polymorphism at position 49 in exon 1 of the CTLA4 gene, providing a A-G exchange. This polymorphism is reportedly associated with type 1 diabetes in Caucasians but not in a small data set of Chinese. We wished to test this polymorphism in a larger and more homogeneous data set of Chinese children with type 1 diabetes and normal adult controls. DESIGN: A population-based case-control study of a CTLA4 gene 49 A-G polymorphism was performed to look for an association with type 1 diabetes in Chinese children. PATIENTS: We analysed this polymorphism in 253 unrelated children (128 boys) with type 1 diabetes (age at diagnosis 7.1 +/- 3.7 years) and 91 randomly selected normal adults. All individuals were Han Chinese. RESULTS: The genotype and gene frequencies of children with type 1 diabetes differed significantly from those of adult controls (P = 0.0091 and P = 0.0051, respectively). Genotype CTLA4 49 G/G and G allele conferred a risk of type 1 diabetes (RR = 2.13, 95% CI = 1.31-3.46, P = 0.0022; RR = 1.68, 95% CI = 1.17-2.43, P = 0.0051, respectively). CONCLUSIONS: This study demonstrates that CTLA4 49 A-G polymorphism is associated with type 1 diabetes in Han Chinese children. The CTLA4 49 G allele confers an increased risk of type 1 diabetes.

Synaptic regulation of L-type Ca(2+) channel activity and long-term depression during refinement of the retinocollicular pathway in developing rodent superior colliculus.

The retinocollicular pathway undergoes activity-dependent refinement during postnatal development, which results in the precise retinotopic order seen in adults. This process is NMDA- and nitric oxide-dependent. Recent studies have shown that L-type Ca2+ channels may also play a role in synaptic plasticity, but such channel activity has not previously been reported in the developing superior colliculus (SC). Here we report the presence of a postsynaptic plateau potential mediated by L-type Ca2+ channels using whole-cell current clamp of the SC in an isolated brainstem preparation of rats. Seventy percent of SC neurons showed these potentials as early as postnatal day 0 (P0)-P2. The potential was blocked by nitrendipine and/or APV and facilitated by bicuculline, showing that the channel is activated by NMDA receptor-mediated EPSPs and deactivated by GABAA receptor-mediated IPSPs. Blockade of L-type Ca2+ channels also diminished long-term depression, which we could induce in the retinocollicular pathway in neonatal animals. The incidence of plateau potentials decreased to 39% of neurons by P10-P14, suggesting that L-type calcium channels may contribute to retinocollicular pathway refinement in the developing SC.

Electrophysiological properties and synaptic responses of cells in the trigeminal principal sensory nucleus of postnatal rats.

In the rodent brain stem trigeminal complex, select sets of neurons form modular arrays or "barrelettes," that replicate the patterned distribution of whiskers and sinus hairs on the ipsilateral snout. These cells detect the patterned input from the trigeminal axons that innervate the whiskers and sinus hairs. Other brain stem trigeminal cells, interbarrelette neurons, do not form patterns and respond to multiple whiskers. We examined the membrane properties and synaptic responses of morphologically identified barrelette and interbarrelette neurons in the principal sensory nucleus (PrV) of the trigeminal nerve in early postnatal rats shortly after whisker-related patterns are established. Barrelette cell dendritic trees are confined to a single barrelette, whereas the dendrites of interbarrelette cells span wider territories. These two cell types are distinct from smaller GABAergic interneurons. Barrelette cells can be distinguished by a prominent transient A-type K(+) current (I(A)) and higher input resistance. On the other hand, interbarrelette cells display a prominent low-threshold T-type Ca(2+) current (I(T)) and lower input resistance. Both classes of neurons respond differently to electrical stimulation of the trigeminal tract. Barrelette cells show either a monosynaptic excitatory postsynaptic potential (EPSP) followed by a large disynaptic inhibitory postsynaptic potential (IPSP) or just simply a disynaptic IPSP. Increasing stimulus intensity produces little change in EPSP amplitude but leads to a stepwise increase in IPSP amplitude, suggesting that barrelette cells receive more inhibitory input than excitatory input. This pattern of excitation and inhibition indicates that barrelette cells receive both feed-forward and lateral inhibition. Interbarrelette cells show a large monosynaptic EPSP followed by a small disynaptic IPSP. Increasing stimulus intensity leads to a stepwise increase in EPSP amplitude and the appearance of polysynaptic EPSPs, suggesting that interbarrelette cells receive excitatory inputs from multiple sources. Taken together, these results indicate that barrelette and interbarrelette neurons can be identified by their morphological and functional attributes soon after whisker-related pattern formation in the PrV.

Three GABA receptor-mediated postsynaptic potentials in interneurons in the rat lateral geniculate nucleus.

Inhibition is crucial for the thalamus to relay sensory information from the periphery to the cortex and to participate in thalamocortical oscillations. However, the properties of inhibitory synaptic events in interneurons are poorly defined because in part of the technical difficulty of obtaining stable recording from these small cells. With the whole-cell recording technique, we obtained stable recordings from local interneurons in the lateral geniculate nucleus and studied their inhibitory synaptic properties. We found that interneurons expressed three different types of GABA receptors: bicuculline-sensitive GABA(A) receptors, bicuculline-insensitive GABA(A) receptors, and GABA(B) receptors. The reversal potentials of GABA responses were estimated by polarizing the membrane potential. The GABA(A) receptor-mediated responses had a reversal potential of approximately -82 mV, consistent with mediation via Cl(-) channels. The reversal potential for the GABA(B) response was -97 mV, consistent with it being a K(+) conductance. The roles of these GABA receptors in postsynaptic responses were also examined in interneurons. Optic tract stimulation evoked a disynaptic IPSP that was mediated by all three types of GABA receptors and depended on activation of geniculate interneurons. Stimulation of the thalamic reticular nucleus evoked an IPSP, which appeared to be mediated exclusively by bicuculline-sensitive GABA(A) receptors and depended on the activation of reticular cells. The results indicate that geniculate interneurons form a complex neuronal circuitry with thalamocortical and reticular cells via feed-forward and feedback circuits, suggesting that they play a more important role in thalamic function than thought previously.

Retinal input induces three firing patterns in neurons of the superficial superior colliculus of neonatal rats.

By using an in vitro isolated brain stem preparation, we recorded extracellular responses to electrical stimulation of the optic tract (OT) from 71 neurons in the superficial superior colliculus (SC) of neonatal rats (P1-13). At postnatal day 1 (P1), all tested neurons (n = 10) already received excitatory input from the retina. Sixty-nine (97%) superficial SC neurons of neonatal rats showed three response patterns to OT stimulation, which depended on stimulus intensity. A weak stimulus evoked only one spike that was caused by activation of non-N-methyl-D-aspartate (NMDA) glutamate receptors. A moderate stimulus elicited a short train (<250 ms) of spikes, which was induced by activation of both NMDA and non-NMDA receptors. A strong stimulus gave rise to a long train (>300 ms) of spikes, which was associated with additional activation of L-type high-threshold calcium channels. The long train firing pattern could also be induced either by temporal summation of retinal inputs or by blocking gamma-aminobutyric acid-A receptors. Because retinal ganglion cells show synchronous bursting activity before eye opening at P14, the retinotectal inputs appear to be sufficient to activate L-type calcium channels in the absence of pattern vision. Therefore activation of L-type calcium channels is likely to be an important source for calcium influx into SC neurons in neonatal rats.

HLA DQA1 genotyping of Chinese in Taiwan by PCR-RFLP.

Population data were established for the HLA DQA1 locus among 147 Chinese in Taiwan by the PCR-RFLP flowchart system. Twelve alleles could be differentiated in this study, although only nine alleles were found among the above samples. There were no discrepancies in the results obtained by PCR-RFLP when compared to the results obtained by the AmpliType HLA DQ alpha typing kit. Using the Chi-square test, significant differences were observed (p < 0.005) between this data and that for Japanese, African Americans and US Caucasians. The observed heterozygosity was 83% with a discrimination power of 0.93.

Control of recurrent inhibition of the lateral posterior-pulvinar complex by afferents from the deep layers of the superior colliculus of the rabbit.

We investigated the effect of stimulation of the deep layers of the superior colliculus (SC) on the recurrent inhibition of the lateral posterior-pulvinar complex (LP) in anesthetized rabbits. Intracellular recordings from 23 relay cells in LP showed that they responded to SC stimulation with a long-lasting (140.2 +/- 19.6 ms; mean +/- SD) inhibitory postsynaptic potential (IPSP), which sometimes was followed by a rebound burst of spikes. The same SC stimulation evoked a burst of spikes in extracellular recordings from 31 recurrent inhibitory interneurons in the LP-cortical pathway, which were located in the ventral part of the visual sector of the thalamic reticular nucleus. The mean latency of the burst in reticular cells was 1.6 ms shorter than that of the IPSP in LP relay cells, suggesting that the IPSP in LP cells was mediated by these reticular cells. Intracellular recordings from nine reticular cells showed that the burst of spikes evoked by SC stimulation resulted from an excitatory postsynaptic potential that was always followed by a long-lasting (143.3 +/- 24.0 ms) IPSP. Stimulation of the contralateral predorsal bundle, the main output pathway of deep SC neurons, elicited similar responses in LP cells or reticular neurons with latencies longer than those from SC stimulation. The latency difference between the responses to predorsal bundle and SC stimulation is equal to the antidromic conduction time of predorsal bundle fibers, suggesting that the inhibition in LP originates from the activation of predorsal bundle-projecting neurons. The response characteristics of the inhibitory circuit of LP and of the lateral geniculate nucleus to SC stimulation are strikingly similar, implying that a similar circuit is used by predorsal bundle-projecting neurons to control the recurrent inhibition in both lateral geniculate nucleus and LP. Because the predorsal bundle-projecting neurons are believed to be involved in the initiation of saccadic eye movements, we suggest that the inhibitory circuits may play an important role in modulating ascending visual information during saccadic eye movements.

Physiological properties of neurons in the optic layer of the rat's superior colliculus.

We made intracellular recordings from 74 neurons in the optic layer of the rat superior colliculus (SC). Resting membrane potentials were -62.3 +/- 6.2 (SD) mV, and input resistances were 37.9 +/- 10.1 MOmega. Optic layer neurons had large sodium spikes (74.2 +/- 12.3 mV) with an overshoot of 12 mV and a half-amplitude duration of 0.75 +/- 0.2 ms. Each sodium spike was followed by two afterhyperpolarizations (AHPs), one of short duration and one of longer duration, which were mediated by tetraethylammonium (TEA)-sensitive (IC) or apamin-sensitive (IAHP) calcium-activated potassium currents, respectively. Sodium spikes were also followed by an afterdepolarization (ADP), which was only revealed when the AHPs were blocked by TEA or apamin. In response to hyperpolarizing current pulses, optic layer neurons showed an inward rectification mediated by H channels. At the break of the current pulse, there was a rebound low-threshold spike (LTS) with a short duration of <25 ms. The LTS usually induced two sodium spikes (doublet). Most optic layer neurons (84%) behaved as intrinsically bursting cells. They responded to suprathreshold depolarization with an initial burst (or doublet) followed by a train of regular single spikes. The remaining 16% of cells acted as chattering cells with high-frequency gamma (20-80 Hz) rhythmic burst firing within a narrow range of depolarized potentials. The interburst frequency was voltage dependent and also time dependent, i.e., showed frequency adaptation. Unmasking the ADP with either TEA or apamin converted all of the tested intrinsically bursting cells into chattering cells, indicating that the ADP played a crucial role in the generation of rhythmic burst firing. Optic layer neurons receive direct retinal excitation mediated by both N-methyl--aspartate (NMDA) and non-NMDA receptors. Optic tract (OT) stimulation also led to gamma-aminobutyric acid-A (GABAA) receptor-mediated inhibition, the main effect of which was to curtail the excitatory response to retinal inputs by shunting the excitatory postsynaptic current. Intracellular staining with biocytin showed that the optic layer neurons that we recorded from were mostly either wide-field vertical neurons or other cells with predominately superficially projecting dendrites. These cells were similar to calbindin immunoreactive cells seen in the optic layer. The characteristics of these optic layer neurons, such as prominent AHPs, strong shunting effect of inhibition, and short-lasting LTS, suggest that they respond transiently to retinal inputs. This is consistent with a function for these cells as the first relay station in the extrageniculate visual pathway.

DQA1*Arg52,DQB1*nonAsp57, and DRB1*04 genotypes in Chinese children with insulin-dependent diabetes mellitus.

Ethnic comparisons are extremely important and useful for studying the HLA component involved in insulin-dependent diabetes mellitus (IDDM) predisposition. To date there have been only a few reports on the association of HLA loci and IDDM in Chinese. We report here a study on DQA1*Arg52, DQB1*nonAsp57, and DRB1*04 in IDDM children and control adults among Han Chinese living in Taiwan. One hundred and fourteen unrelated children (62 boys) with IDDM were studied. Their ages at diagnosis were between 0.3 and 15.0 years (6.8 +/- 3.6 years). The control population consisted of 120 randomly selected normal adults. DQA1*Arg52(+/+), DQB1*nonAsp57(+/+), and DRB1*04(+/-) were associated with IDDM (RR = 11.50, 2.21, and 2.82; p = 1.11 x 10(-15), 2.84 x 10(-3), and 1.98 x 10(-4), respectively). DQA1*Arg52, DQB1*nonAsp57, and DRB1*04 conferred risks for IDDM (RR = 12.79, 7.11, and 2.83; pc = 8.22 x 10(-4), 5.35 x 10(-3), and 5.68 x 10(-4), respectively). Combinations of DQA1*Arg52 and DRB1*04 conferred the highest risk for IDDM (RR = 19.64, pc = 5.4 x 10(-5)). DQA1*Arg52 was associated with IDDM in subjects with DQB1*nonAsp57+ (RR = 14.87, pc = 2.41 x 10(-4)) and DQB1*nonAsp57 was also associated with IDDM in subjects with DQA1*Arg52+ (RR = 8.41, pc = 1.54 x 10(-3)), suggesting that DQA1*Arg52 and DQB1*nonAsp57 are interacting. This study demonstrates that DQA1*Arg52, DQB1*nonAsp57, and DRB1*04 confer susceptibility for IDDM to Chinese children. A combination of DQA1*Arg52 and DRB1*04 confers the highest risk and it is suggested that a susceptibility gene might be situated between DQA1*Arg52 and DRB1*04 or both are synergistic. There is an interaction between DQA1*Arg52 and DQB1*nonAsp57 and homozygosity for DQA1*Arg52/DQB1*nonAsp57, which encodes four susceptibility DQ heterodimers, confers a high risk.