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Biomedical subjects

D D Lee

Publications and source records attributed to D D Lee.

At least 19 recordsLinked to original sources
PubMed2003

SPR1 gene near HLA-C is unlikely to be a psoriasis susceptibility gene.

Although genetics analyses have identified the HLA-Cw6 allele to be the major risk allele for psoriasis vulgaris (PV) in many racial groups, it has been proposed that other putative genes near the HLA-C locus are involved in PV susceptibility and that the association of Cw6 is a result of linkage disequilibrium. The SPR1 gene, a predicted gene located 128 kb telomeric to the HLA-C locus, is considered to be one potential candidate gene of PV. Until now, no association study of the SPR1 gene has been conducted on psoriasis patients. We investigated the SPR1 gene for disease association by direct sequencing of the SPR1 gene in 116 Chinese patients with PV and 116 normal subjects. Genotyping for HLA-Cw6 was also carried out using polymerase chain reaction/restriction fragment length polymorphism. Significant increase of the HLA-Cw6 allele was found in psoriasis patients (32.8% vs. 13.8%, P = 0.001). We found that the SPR1 gene is a highly polymorphic gene containing 13 single nucleotide polymorphisms (SNPs), two of which have not been previously reported, and four SNPs cause amino acid change. No significantly different allelic distribution of 13 SPR1 SNPs could be found between the patients with PV and controls after correction for multiple testing. If the frequencies of SPR1 SNPs were compared between the early onset psoriatics and control subjects, early onset patients were more likely to have G allele at position 988 (60% vs. 35.3%, P = 0.001). However, the significance disappeared upon stratification for the Cw6 status. Haplotype-based association analysis showed two susceptibility haplotypes (types 8 and 19) in early onset psoriasis patients. Nonetheless, the significance also disappeared after stratification of the Cw6 status. Our results suggest that HLA-Cw6 remains the major risk allele in Chinese psoriatics, and that the SPR1 gene might not play an important role in the causation of PV.

Adult↗
PubMed2003

A study of candidate genes for psoriasis near HLA-C in Chinese patients with psoriasis.

BACKGROUND: Genetic analyses have identified the HLA-Cw6 allele as the major risk allele for psoriasis in many racial groups. However, by serological typing, HLA-Cw6 is not considered a risk factor in Chinese psoriatics. There are several susceptibility genes for psoriasis residing in chromosome 6p near the HLA-C locus, including the corneodesmosin (CDSN) gene, the octamer transcription factor-3 (POU5F1) gene, the major histocompatibility complex class I chain-related gene A (MICA), and the gene for tumour necrosis factor (TNF)-alpha. However, the information about their role in psoriasis in Chinese patients is limited. OBJECTIVES: We aimed to determine whether Cw6 and the genetic polymorphism of the CDSN gene, POU5F1 gene, MICA gene and the gene for TNF-alpha promoter region were associated with an increased risk of psoriasis in Chinese patients. METHODS: We conducted a case-control association study in 105 Chinese patients with psoriasis vulgaris and 160 control subjects of similar ages. Genotypes of Cw6, the CDSN gene, the POU5F1 gene, and the gene for the TNF-alpha promoter region were determined by polymerase chain reaction (PCR) followed by restriction enzyme digestion. Genotyping of MICA was determined by PCR combined with fluorescent-based automated fragment detection technology. Results The allele frequencies showed no differences between patients and controls for the POU5F1 gene, MICA gene and the gene for TNF-alpha promoter region. The frequency of the HLA-Cw6 allele in the psoriasis group was significantly higher than that in the control group (18.6% vs. 6.56%, P < 0.00005). For the CDSN gene, patients were more likely to have C allele at position +619 (P = 0.006) and C allele at position +1243 (P = 0.007), but the significance disappeared after correction for multiple testing (Pc > 0.05). CONCLUSIONS: HLA-Cw6 remains the most significant susceptibility gene in Chinese patients with psoriasis. However, the role of the CDSN gene in the pathogenesis of psoriasis deserves further scrutiny.

Adolescent↗
PubMed2001

Equilibrium properties of temporally asymmetric Hebbian plasticity.

A theory of temporally asymmetric Hebb rules, which depress or potentiate synapses depending upon whether the postsynaptic cell fires before or after the presynaptic one, is presented. Using the Fokker-Planck formalism, we show that the equilibrium synaptic distribution induced by such rules is highly sensitive to the manner in which bounds on the allowed range of synaptic values are imposed. In a biologically plausible multiplicative model, the synapses in asynchronous networks reach a distribution that is invariant to the firing rates of either the presynaptic or postsynaptic cells. When these cells are temporally correlated, the synaptic strength varies smoothly with the degree and phase of their synchrony.

Animals↗
PubMed2001

Clinical and histopathological characteristics of primary cutaneous amyloidosis in 794 Chinese patients.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is not uncommon in Chinese patients. The disease is usually persistent and quite pruritic. Patients who suffer from this disease usually respond poorly to conventional treatment. We thus reviewed our cases of PCA to discuss the clinical and pathological characteristics. METHODS: Seven hundred and ninety-four Chinese patients with PCA who visited the Department of Dermatology, Taipei Veterans General Hospital during the last 26-year period were examined and retrospectively studied. The diagnosis in these patients was confirmed by histopathological studies. RESULTS: Among the many types of PCA, lichen amyloidosis was the most common clinical variant (67%). Pure cases of macular amyloidosis accounted only 8% and were often associated with lichenoid lesions to form biphasic amyloidosis, which was composed of 25% in our series. Other rare types of PCA, such as nodular, anosacral, and vitiliginous amyloidosis, always required a careful differential diagnosis clinically from other similar skin disorders. In addition, 56 familial cases were found. Histopathologically, the most common epidermal findings of PCA were hyperkeratosis, irregular acanthosis with thinning of rete ridges, and expansion of dermal papillae by amyloid deposition. Special histochemical stains were helpful for confirming the existence of amyloid. CONCLUSIONS: Our study represents the largest number of cases of PCA collected to date. Based on the data, most cases are sporadic, except 56 familial cases which may suggest the possible genetic role. Rare types of PCA, such as anosacral and vitiliginous amyloidosis which need special attention, compose a diagnostic challenge to a dermatologist. Histochemically, H&E stain can give a primary clue for the diagnosis of amyloidosis and crystal violet stain is a very simple and sensitive method to detect the existence of amyloid.

Adult↗
PubMed2000

Cognition. The manifold ways of perception.

One of the great puzzles of visual perception is how an image that is in perpetual flux can still be seen by the observer as the same object. In an informative Perspective, Seung and Lee explain the mathematical intricacies of two new algorithms for modeling the variability of perceptual stimuli and other types of high-dimensional data (Tenenbaum et al., and Roweis and Saul).

Algorithms↗
PubMed2000

Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia.

Inactivation of the beta4 subunit of the calcium channel in the mouse neurological mutant lethargic results in a complex neurological disorder that includes absence epilepsy and ataxia. To determine the role of the calcium-channel beta4-subunit gene CACNB4 on chromosome 2q22-23 in related human disorders, we screened for mutations in small pedigrees with familial epilepsy and ataxia. The premature-termination mutation R482X was identified in a patient with juvenile myoclonic epilepsy. The R482X protein lacks the 38 C-terminal amino acids containing part of an interaction domain for the alpha1 subunit. The missense mutation C104F was identified both in a German family with generalized epilepsy and praxis-induced seizures and in a French Canadian family with episodic ataxia. These coding mutations were not detected in 255 unaffected control individuals (510 chromosomes), and they may be considered candidate disease mutations. The results of functional tests of the truncated protein R482X in Xenopus laevis oocytes demonstrated a small decrease in the fast time constant for inactivation of the cotransfected alpha1 subunit. Further studies will be required to evaluate the in vivo consequences of these mutations. We also describe eight noncoding single-nucleotide substitutions, two of which are present at polymorphic frequency, and a previously unrecognized first intron of CACNB4 that interrupts exon 1 at codon 21.

Amino Acid Sequence↗
PubMed2000

Stability of the memory of eye position in a recurrent network of conductance-based model neurons.

Studies of the neural correlates of short-term memory in a wide variety of brain areas have found that transient inputs can cause persistent changes in rates of action potential firing, through a mechanism that remains unknown. In a premotor area that is responsible for holding the eyes still during fixation, persistent neural firing encodes the angular position of the eyes in a characteristic manner: below a threshold position the neuron is silent, and above it the firing rate is linearly related to position. Both the threshold and linear slope vary from neuron to neuron. We have reproduced this behavior in a biophysically plausible network model. Persistence depends on precise tuning of the strength of synaptic feedback, and a relatively long synaptic time constant improves the robustness to mistuning.

Animals↗
PubMed2000

Comparison of pharmacokinetics of fentanyl after intravenous and transdermal administration in cats.

OBJECTIVE: To compare pharmacokinetic and pharmacodynamic characteristics of fentanyl citrate after IV or transdermal administration in cats. ANIMALS: 6 healthy adult cats with a mean weight of 3.78 kg. PROCEDURE: Each cat was given fentanyl IV (25 mg/cat; mean +/- SD dosage, 7.19 +/- 1.17 mg/kg of body weight) and via a transdermal patch (25 microg of fentanyl/h). Plasma concentrations of fentanyl were measured by use of radioimmunoassay. Pharmacokinetic analyses of plasma drug concentrations were conducted, using an automated curve-stripping process followed by nonlinear, least-squares regression. Transdermal delivery of drug was calculated by use of IV pharmacokinetic data. RESULTS: Plasma concentrations of fentanyl given IV decreased rapidly (mean elimination half-life, 2.35 +/- 0.57 hours). Mean +/- SEM calculated rate of transdermal delivery of fentanyl was 8.48 +/- 1.7 mg/h (< 36% of the theoretical 25 mg/h). Median steady-state concentration of fentanyl 12 to 100 hours after application of the transdermal patch was 1.58 ng/ml. Plasma concentrations of fentanyl < 1.0 ng/ml were detected in 4 of 6 cats 12 hours after patch application, 5 of 6 cats 18 and 24 hours after application, and 6 of 6 cats 36 hours after application. CONCLUSIONS AND CLINICAL RELEVANCE: In cats, transdermal administration provides sustained plasma concentrations of fentanyl citrate throughout a 5-day period. Variation of plasma drug concentrations with transdermal absorption for each cat was pronounced. Transdermal administration of fentanyl has potential for use in cats for long-term control of pain after surgery or chronic pain associated with cancer.

Administration, Topical↗
PubMed1999

C(60) and water-soluble fullerene derivatives as antioxidants against radical-initiated lipid peroxidation.

C(60), vitamin E, and three C(60) derivatives (polar 1 and water-soluble C(3)/D(3)C(60)s) were examined for their antioxidant effects on prevention of lipid peroxidation induced by superoxide and hydroxyl radicals. The protection effect on lipid peroxidation was found to be in the sequence: C(60) >/= vitamin E > 1 > none, for liposoluble antioxidants, and C(3)C(60) >> D(3)C(60) > none, for water-soluble ones. Fluorescence quenching of PyCH(2)COOH (Py = pyrene) by both C(3)- and D(3)C(60)s shows that the Stern-Volmer constant, K(SV), is about the same for both quenchers in aqueous solution. Upon addition of liposomes, the fluorescence quenching becomes more efficient: 5-fold higher in K(SV) for C(3)C(60) than for D(3)C(60). When Py(CH(2))(n)()COOH (n = 1, 3, 5, 9, or 15) was incorporated in lipid membranes, the K(SV)s all were small and nearly equal for D(3)C(60) but were quite large and different for C(3)C(60) with the sequence: n = 1 < 3 < 5 < 9 < 15. The better protection effect of C(3)C(60) on lipid peroxidation than that of D(3)C(60) is attributed to its stronger interaction with membranes. Overall, the antioxidation abilities of the compounds examined were rationalized in terms of the number of reactive sites, the location of antioxidant in lipid membranes, and the strength of interactions between antioxidants and membranes.

Antioxidants↗
PubMed1999

Learning the parts of objects by non-negative matrix factorization.

Is perception of the whole based on perception of its parts? There is psychological and physiological evidence for parts-based representations in the brain, and certain computational theories of object recognition rely on such representations. But little is known about how brains or computers might learn the parts of objects. Here we demonstrate an algorithm for non-negative matrix factorization that is able to learn parts of faces and semantic features of text. This is in contrast to other methods, such as principal components analysis and vector quantization, that learn holistic, not parts-based, representations. Non-negative matrix factorization is distinguished from the other methods by its use of non-negativity constraints. These constraints lead to a parts-based representation because they allow only additive, not subtractive, combinations. When non-negative matrix factorization is implemented as a neural network, parts-based representations emerge by virtue of two properties: the firing rates of neurons are never negative and synaptic strengths do not change sign.

Algorithms↗
PubMed1999

alpha-BSM: a biomimetic bone substitute and drug delivery vehicle.

alpha-BSM is a biomimetic endothermically setting apatitic calcium phosphate bone substitute material. Its injectability and ability to harden at body temperature in the presence of physiologic saline, and other buffering agents, makes it an attractive clinical bone substitute and delivery vehicle for therapeutic agents in orthopaedic and dental applications. In osseous tissue, alpha-BSM alone remodels into bone and promotes bone healing. alpha-BSM treatment has been shown in several animal models to be effective in promoting healing of surgically created critical size defects and restoring bone biomechanical strength to values equal to or greater than values achieved with autograft controls. In vitro studies with alpha-BSM containing gentamicin show that antibiotics can be incorporated stably into alpha-BSM and that the release kinetics can be controlled with the appropriate formulation and preparative procedures. Growth factors and enzymes also are compatible with the alpha-BSM setting reaction. The incorporation of recombinant human bone morphogenetic protein-2 with alpha-BSM was shown to be effective in stimulating bone formation and accelerating restoration of the differentiated phenotype in an osteotomy model. Clinical trial investigators in Europe currently are using alpha-BSM implantations for treatment of fractures and other indications.

Animals↗
PubMed1998

Resorbable calcium phosphate bone substitute.

The in vitro and in vivo properties of a novel, fully resorbable, apatitic calcium phosphate bone substitute (ABS) are described. The ABS was prepared from calcium phosphate precursors that were hydrated to form an injectable paste that hardens endothermically at 37 degrees C to form a poorly crystalline apatitic calcium phosphate (PCA). The PCA reaction product is stable in vivo as determined by FTIR and XRD analysis of rabbit intramuscular implants of ABS retrieved 4, 7, and 14 days postimplantation. Bone formation and resorption characteristics of the ABS material were characterized in a canine femoral slot defect model. Femoral slot defects in dogs were filled with either autologous bone implants or the ABS material. Sections of femoral bone defect site from animals sacrificed at 3, 4, 12, 26, and 52 weeks demonstrated that new bone formation proceeded similarly in both autograft and ABS filled slots. Defects receiving either material were filled with trabecular bone in the first 3 to 4 weeks after implantation; lamellar or cortical bone formation was well established by week 12. New bone formation in ABS filled defects followed a time course comparable to autologous bone graft filled defects. Histomorphometric evaluation of ABS resorption and new bone formation indicated that the ABS material was greater than 99% resorbed within 26 weeks; residual ABS occupied 0.36+/-0.36% (SEM, n = 4) of the original defect area at 26 weeks. Quantitatively and qualitatively, the autograft and ABS were associated with similar new bone growth and defect filling characteristics.

Animals↗
PubMed1998

Dermatopathologic findings in 20 cases of systemic amyloidosis.

The clinical findings of systemic amyloidosis are often variable and nonspecific. The early recognition of this disorder relies upon clinical suspicion, and definite diagnosis requires the confirmation of amyloid deposits in tissue. We reviewed 31 skin biopsy specimens from 20 patients, including 17 with amyloid light chain (AL) protein amyloidosis and 3 with serum amyloid A (AA) protein amyloidosis. Histologically, amyloid can be present in the papillary dermis, reticular dermis, subcutis, around the appendages, and in or around blood vessels. In our series, all 20 patients had at least one positive skin biopsy. Amyloid was found in 30 of 31 specimens (97%), a higher rate than in most series. Skin biopsy is a simple, safe procedure with high yield and may be used to obtain a firm diagnosis of systemic amyloidosis.

Aged↗
PubMed1996

General principles of anesthesia and sedation in food animals.

Minimal-risk anesthesia practice demands that fundamental physiologic and pharmacologic principles be applied to the specific medical and surgical needs of individual patients. In developing an anesthesia plan for a patient, health status must be assessed and considered along with other extrinsic factors such as the physical setting in which the anesthetic procedure will be performed, the availability of equipment and supplies, and the academic and technical training and abilities of participating personnel. This article reviews considerations for developing anesthesia protocols for ruminant and swine species.

Anesthesia↗
PubMed1996

Genetic heterogeneity of familial primary cutaneous amyloidosis: lack of evidence for linkage with the chromosome 10 pericentromeric region in Chinese families.

Primary cutaneous amyloidosis is a relatively common skin disease in Southeast Asia, South America, and the Republic of China. Although most cases are sporadic, some patients have a family history, suggesting that genetic factors may play a role in its pathogenesis. Some patients with multiple endocrine neoplasia type 2A also have a clinical picture of primary cutaneous amyloidosis. It is thus suggested that the gene of familial primary cutaneous amyloidosis is linked to the pericentromeric region of chromosome 10, the location of the RET proto-oncogene. We have carried out linkage analysis in seven families with cutaneous amyloidosis using four dinucleotide repeat markers from the RET region. Negative lod scores at all recombination frequencies were obtained. We thus conclude that there is no evidence for linkage between Chinese families with primary cutaneous amyloidosis and the pericentromeric region of chromosome 10. The distinct genetic basis, plus their apparent phenotypic differences in sex ratio, age of onset, and sites of cutaneous lesions, suggests that familial primary cutaneous amyloidosis includes clinical subtypes attributable to genetic heterogeneity.

Adolescent↗
PubMed1996

Systemic amyloidosis with initial polyneuropathy.

We report a case of systemic amyloidosis with the initial sign of polyneuropathy. The patient eventually developed heart failure, macroglossia, and ecchymoses 6 years later. Biopsies from the sural nerve and normal-looking skin both proved the existence of amyloid.

Aged↗