Annular pustular psoriasis localized to the dorsa of the feet.
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Biomedical subjects
Publications and source records attributed to H Kang.
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Several loci and candidate genes for epilepsies or epileptic syndromes map or have been suggested to map to chromosome 8. We investigated families with adolescent-onset idiopathic generalized epilepsy (IGE), for linkage to markers spanning chromosome 8. The IGEs that we studied included juvenile myoclonic epilepsy (JME), epilepsy with only generalized tonic-clonic seizures occurring either randomly during the day (random grand mal) or on awakening (awakening grand mal), and juvenile absence epilepsy (JAE). We looked for a gene common to all these IGEs, but we also investigated linkage to specific subforms of IGE. We found evidence for linkage to chromosome 8 in adolescent-onset IGE families in which JME was not present. The maximum multipoint LOD score was 3.24 when family members with IGE or generalized spike-and-waves (SW) were considered affected. The LOD score remained very similar (3.18) when clinically normal family members with SW were not considered to be affected. Families with either pure grand mal epilepsy or absence epilepsy contributed equally to the positive LOD score. The area where the LOD score reaches the maximum encompasses the location of the gene for the beta3-subunit of the nicotinic acetylcholine receptor (CHRNB3), thus making this gene a possible candidate for these specific forms of adolescent-onset IGE. The data excluded linkage of JME to this region. These results indicate genetic heterogeneity within IGE and provide no evidence, on chromosome 8, for a gene common to all IGEs.
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A 32-year-old woman with a long-standing systemic lupus erythematosus had multiple subcutaneous nodules on her axillae, iliac crests and limbs. Three years ago, these nodules began to appear and slowly became larger. Some of them amassed to form a large, fungating, lobulated mass on her right iliac crest. Roentgenographic and histological examination showed that they were calcium deposits. She was initially treated with aluminum hydroxide administration for nine months, which resulted in moderate decrease in size and softening in consistency, but not complete resolution. Then, the mass on the right iliac crest was excised, with an excellent early result.
OBJECTIVE: To describe the demographic characteristics and postwar health status of U.S. Gulf War veterans who participated in the Department of Veterans Affairs health examination registry program. DESIGN: Case records of 52,835 veterans who participated in a standardized health examination program were reviewed. SETTING: Participants volunteered for physical examinations at a Department of Veterans Affairs medical treatment facility from August 1992 to September 1996. SUBJECTS: U.S. Gulf War veterans deployed to southwest Asia between August 1990 and 1996. MAIN OUTCOME MEASURE: Demographic, military, symptom, and International Classification of Diseases, Ninth Revision, Clinical Modification, diagnostic categories. RESULTS: A wide variety of symptoms and diagnoses were reported without apparent internal variation by military characteristics (branch and service component). The frequency of symptoms (fatigue, skin rash, headache, muscle and joint pain, and memory loss) reported increased over time, whereas the proportion of individuals with physician-diagnosed illnesses remained fairly constant. No single category of disease increased or decreased substantially over time. CONCLUSIONS: Veterans have experienced a wide variety of health problems since their Gulf War service. These problems, in aggregate, are different from what has been seen in other armed conflicts. The Department of Veterans Affairs registry is a very large case series and has failed to identify a single, unique syndrome or new illness after Gulf War service. An epidemiologic study would better define the prevalence of specific symptoms and medical conditions among Gulf War veterans and to what extent any of the conditions identified are associated with Gulf War military service. The knowledge provided by such studies would be important to development of preventive measures and future deployment medical surveillance planning.
Tensile mechanical experiments were made on 31 lateral capsular-ligament complex spencimens from 8 fresh temporomandibular joints of human cadavers aged 8-15 years. The tests included stress relaxation at different strain rates and tension test at constant strain rate. Some biomechanical material properties of the tissue were determined. The result showed that the complex had lower tensile strength and tensile stiffness, and the stress relaxatioin was the most important mechanism of spreading stress and absorbing shock. The stress relaxation function and the constitutive equation of stress and strain were obtained with Fung's Quasi-Linear Viscoelastic Theory fitting the experimental results.
TcRzeta/CD3 ligation initiates a signaling cascade involving CD4/CD8-p56(lck), p59(fyn), and ZAP-70, as well as lymphoid downstream proteins VAV, SLP-76, and FYB/SLAP. A current question concerns the nature of the downstream binding partner(s) of FYB in T cells. In this study, using a two-hybrid screen with FYB as bait, we have identified eight clones, four of which correspond to the recently published lymphoid protein SKAP55, and two which correspond to a related protein with some 44% homology to SKAP55 (termed SKAP55-related protein, SKAP55R). The SKAP55 clones showed only minor differences (two substitutions and one residue deletion) from SKAP55. SKAP55R has the same overall structure as SKAP55 except for the presence of a unique N terminus with a well-defined coiled-coil domain. Both SKAP55 and SKAP55R were found to bind FYB through their SH3 domains and to act as substrates for the FYN kinase in T cells. Furthermore, immunofluorescence confocal microscopy showed that FYB and SKAP55 colocalize in the perinuclear region of cells. SKAP55 also colocalizes with another FYB binding protein, SLP-76. Taken together, these observations demonstrate that FYB is part of an interactive matrix with SKAP55 and a SKAP55-related protein.
The retinoblastoma protein may function as a tumor suppressor by controlling the progression of the normal cell cycle. Inactivation of Rb has been regarded as an important event in prostate carcinogenesis. However, the detailed mechanism of how Rb is linked to androgen-androgen receptor (A-AR), the major factor in promotion of prostate tumor growth, remains unclear. Using GST-Rb pull down assay and mammalian two-hybrid system, we report here that Rb can bind specifically to AR in an androgen-independent manner. Transient transfection assay demonstrates that cotransfection of AR and Rb can further induce AR transcriptional activity 4-fold in the presence of 1 nM dihydrotestosterone in DU145 cells. Interestingly, cotransfection of Rb and ARA70, the first identified AR coactivator, with AR can additively induce AR transcriptional activity 13-fold (from 5-fold to 64-fold). In conclusion, our discovery that Rb can function as a coactivator to induce AR transcriptional activity in prostate cells may represent the first data to link a negative growth regulatory protein function in a positive manner, by inducing the transcriptional activity of AR.
To identify a polyamine-conjugated protein by the action of transglutaminase in the absence of radiolabelled polyamine, extracts prepared from the leaves and developing soybean seeds were investigated for the specific activity of transglutaminase and the content of free polyamines. We identified the major storage protein, glycinin, as a polyamine-conjugated protein. This was established by the following procedures: (1) immunolocalization with antibody against putrescine prepared in rabbit against putrescine-BSA conjugate; (2) immunocross-reactivity on nitrocellulose transblot of the purified glycinin subunits by using antibody against putrescine; (3) identification of polyamines in acid hydrolysates of purified glycinin; (4) release of polyamines in proteolytic digests through the catalytic action of gamma-glutamylamine cyclotransferase, an enzyme specific for the disassembly of gamma-glutamylamines. The activity of gamma-glutamylamine cyclotransferase was also identified in soybean seeds.
Nuclear receptors are ligand-modulated transcription factors that respond to steroids, retinoids, and thyroid hormones to control development and body physiology. Orphan nuclear receptors, which lack identified ligands, provide a unique, and largely untapped, resource to discover new principles of physiologic homeostasis. We describe the isolation and characterization of the vertebrate orphan receptor, BXR, which heterodimerizes with RXR and binds high-affinity DNA sites composed of a variant thyroid hormone response element. A bioactivity-guided screen of embryonic extracts revealed that BXR is activatable by low-molecular-weight molecules with spectral patterns distinct from known nuclear receptor ligands. Mass spectrometry and 1H NMR analysis identified alkyl esters of amino and hydroxy benzoic acids as potent, stereoselective activators. In vitro cofactor association studies, along with competable binding of radiolabeled compounds, establish these molecules as bona fide ligands. Benzoates comprise a new molecular class of nuclear receptor ligand and their activity suggests that BXR may control a previously unsuspected vertebrate signaling pathway.
Programmed ribosomal frameshifting in viral messenger RNA occurs in response to neighboring sequence elements consisting of: a frameshift site, a spacer, and a downstream enhancer sequence. In human immunodeficiency virus type 1 (HIV-1) mRNA, this sequence element has a potential to form either a stem-loop or a pseudoknot structure. Based on many mutational studies, the stem-loop structure has been proposed for the downstream enhancer region of the HIV-1 mRNA. This stimulatory stem-loop structure is separated from the shift site by a spacer of seven nucleotides. In contrast, a recent report has proposed an alternative model in which the bases in the spacer sequence form a pseudoknot structure as the downstream enhancer sequence [Du et al., Biochemistry 35 (1996) 4187-4198.]. Using UV melting and enzymatic mapping analyses, we have investigated the conformation of the sequence region involved in ribosomal frameshifting in HIV-1. Our S1, V1, and T1 endonuclease mappings, together with UV melting analysis, clearly indicate that this sequence element of the HIV-1 mRNA frameshift site forms a stem-loop structure, not a pseudoknot structure. This finding further supports the stem-loop structure proposed by many mutational studies for the downstream enhancer sequence of the HIV-1 mRNA.
Mutational effects on frameshifting efficiency of the RNA pseudoknot involved in ribosomal frameshifting in simian retrovirus-1 (SRV-1) have been investigated. The primary sequence and the proposed secondary structure of the SRV-1 pseudoknot are similar to those of other efficient frameshifting pseudoknots in mouse mammary tumor virus (MMTV) and feline immunodeficiency virus (FIV), where an unpaired adenine nucleotide intercalates between stem 1 and stem 2. In SRV-1 pseudoknot, the adenine nucleotide in between stem 1 and stem 2 has a potential to form an A*U base pair with the last uridine nucleotide in the loop 2, resulting in a continuous A-form helix with coaxially stacked stem 1 and stem 2. To test whether this A*U base pairing and coaxial stacking of stem 1 and stem 2 is absolutely required for efficient frameshifting in SRV-1, a series of mutants changing this potential A.U base pair to either G.C base pair or A.A, A.G, A.C, G.A, G.G mismatch is generated, and their frameshifting efficiencies are investigated in vitro using rabbit reticulocyte lysate translation assay. The frameshifting abilities of these mutant pseudoknots are similar to that of the wild-type pseudoknot, suggesting that the A*U base pair in between stem 1 and stem 2 is not necessary to promote efficient frameshifting in SRV-1. These results reveal that coaxial stacking of stem 1 and stem 2 with a Watson-Crick A.U base pair in between two stems is not a required structural feature of the pseudoknot for promoting efficient frameshifting in SRV-1. Our mutational data suggest that SRV-1 pseudoknot adopts similar structural features common to other efficient frameshifting pseudoknots as observed in MMTV and FIV.
Although the lipid kinase phosphatidylinositol 3-kinase (PI-3K) binds at high levels to the cytoplasmic tail of CD28, controversy exists regarding its role in CD28 costimulation. Potentially, the kinase could be linked to a signaling cascade or be needed indirectly in events such as receptor endocytosis. Indeed, little is known regarding both the fate of CD28 following receptor ligation and the events that control the process. In this study, we help to resolve this issue by providing evidence that PI-3K plays a role in regulating CD28 endocytosis. We show that approximately 25 to 35% of wild-type CD28 becomes endocytosed following Ab binding (t1/2 = 10 min), followed by segregation into two pools; one pool is destined for degradation in lysosomal compartments and is blocked by chloroquine, and another pool that is recycled to the cell surface (t1/2 = 2.5 h). Recycling of CD28 could have an important impact on CD80/86-mediated costimulation by replenishing functionally active receptors on the cell surface. Several findings implicate PI-3K in the control of endocytosis. Modulation experiments indicate that CD28-PI-3K complexes are preferentially endocytosed, and mutations that alter PI-3K binding concordantly affect the efficacy of endocytosis. Importantly, mutations that inhibit receptor internalization also block cosignaling. Therefore, previous results documenting a requirement for PI-3K may be explained by a blockage of receptor internalization.
Neuropeptides with similarities to vertebrate tachykinins, designated tachykinin-related peptides (TRPs), have been identified in several insect species. In this investigation we have utilized an antiserum raised to one of the locust TRPs, locustatachykinin-I (LomTK-I), to determine the distribution pattern of LomTK-like immunoreactive (LTKLI) neurons in the developing nervous system of the moth Spodoptera litura. A number of LTKLI neurons could be followed from the larval to the adult nervous system: a set of median neurosecretory cells (MNCs) in the brain, a pair of brain descending neurons and a few sets on neurons in the ventral nerve cord. The distribution of LTKLI neurons in the adult brain is very similar to that seen in other insect species with prominent arborizations in the central body, antennal lobes, mushroom body calyces, optic lobe neuropils and other distinct neuropil areas in the protocerebrum and tritocerebrum. A new finding is the presence of LTKLI neurosecretory cells with axon terminals in the anterior aorta and corpora cardiaca, suggesting for the first time a neurohormonal role of tachykinin-related peptide(s) in insects. During postembryonic development the number of LTKLI neurons in the ventral nerve cord decreases somewhat, whereas the number increases in the brain. Thus the functional roles of TRPs may change to some extent during development.
Antiserum to leucokinin I, a neuropeptide originally isolated from the cockroach Leucophaea maderae, was used for immunocytochemical labeling of neurons in the brain and ventral ganglia of the moth Spodoptera litura during postembryonic development. In the ventral ganglia, leucokinin-like immunoreactivity begins to occur in the abdominal ganglion A3 to A7 of first instar larva. One to two weakly labeled pairs of bilateral LK-LI cell bodies are located in the subesophageal ganglion of fourth to sixth instar larvae and in the abdominal ganglia A1 to A7 of second to sixth instar larvae. The abdominal ganglion A1 of fourth to sixth instar larvae and A8 of sixth instar larva each contain one weakly labeled pair of median LK-LI cell bodies. Two strongly labeled pairs of bilateral LK-LI neurons are found in A3 to A7 of third to sixth instar larvae. Abdominal ganglia A1 to A8 of prepupa, pupa and adult contain one to three weakly labeled pairs of bilateral LK-LI neurons. Two strongly labeled pairs of bilateral LK-LI neurons in each of the abdominal ganglia of larva, prepupa, pupa and adult send axons to the neuropil, and then each axon bifurcates into two axonal branches. Theses axonal branches from two bundles. From each of the two pairs of neurons an axon exits through the posterior ventral nerve (N2) which runs to the transverse nerve of the next posterior segment. In larval brains, 2-16 pairs of bilateral LK-LI cell bodies can be found together with LK-LI processes in the central neuropil. The larval brains show large changes in the number of LK-LI neurons throughout postembryonic development. The number of LK-LI cell bodies are reduced in number from sixth instar larval brain. Therefore, prepupal, pupal and adult brains contain a smaller number of LK-LI cell bodies. Two pairs of LK-LI median neurosecretory cells located immediately beside the pars intercerebralis in larval brains increase to three pairs in the 7-day-old pupal brain. In the adult, however, LK-LI median neurosecretory cells decrease to one pair.
The suppression of T cell responsiveness which occurs after infection with Toxoplasma gondii in mice has been widely studied using spleen cells. Because the natural route of infection with T. gondii is the peroral route, we examined the proliferative responses of mesenteric lymph node (MLN) cells, in addition to spleen cells, to Concanavalin-A (Con-A) in mice perorally infected with T. gondii. Proliferative responses of spleen cells were significantly suppressed seven and ten days after infection when compared with spleen cells from uninfected mice (62% and 91% reduction, respectively). In contrast, proliferative responses of MLN cells from these infected mice did not differ from those of normal MLN cells. Since IFN-gamma-induced reactive nitrogen intermediate (RNI) production has been reported to play a major role in suppression of proliferative responses in spleen cells of infected mice, we compared production of IFN-gamma and RNI by spleen and MLN cells following infection. MLN cells produced as much IFN-gamma as did spleen cells, but produced 70% less nitrite (as a measure of RNI) after Con-A stimulation. Proliferative responses of MLN cells were suppressed when co-cultured with spleen cells from infected mice, and addition of an inhibitor of RNI to these co-culture inhibited this suppression, suggesting that reduced RNI production by MLN cells contributes to their maintenance of higher proliferative responses. These results demonstrated a clear difference in activity of T cells in the MLN and spleen during the acute stage of the infection.
The structural and catalytic role of the N-terminal amino acid sequence of Photinus pyralis luciferase was investigated by site-directed mutagenesis. The firefly luciferase activity of a series of deletion and site-directed mutants in the amino-terminal region was investigated in vitro and in vivo. The mutant luciferases were produced either by in vitro transcription and translation or by expressing the cDNA encoding firefly luciferase in the yeast Saccharomyces cerevisiae as a fusion protein to the galactose DNA binding domain protein. Deleting the N-terminal amino acid residues from 3 to 10 dramatically reduced the luciferase activity to less than 1% of the wild-type activity. A marked decrease in the activity (to < 5%) was also observed with the Lys8Glu mutant. The Gly10Arg and Pro11Ala mutants showed 20-30% activity compared to the wild type. On the other hand, mutant Asn6Lys retained the wild-type activity level. Randomizing 3-11 N-terminal amino acids also showed a marked decrease in activity (< 1%). The mutant luciferases with extremely low levels of enzymatic activity were thermally unstable. These mutational and stability data correlate with the crystal structure of firefly luciferase in which specific amino acids in the N-terminal region form hydrogen bonds to the amino acids in the neighboring beta-stranded sheet. Because the N-terminal region is not part of the active site, the present results suggest that the highly conserved N-terminal amino acid sequences of the firefly luciferase are important for stabilizing the protein in its proper conformation for optimal enzyme activity.
Among 253 cases of nipple discharge, 96 cases of them were diagnosed as intracanalicular papilloma(37.9%), 73 cases as cystic disease of breast(28.9%), 41 cases as mammary duct ectasia (16.2%), 35 cases as breast cancer(13.8%) and 8 cases as acute suppurative mastitis(3.2%). The masses beneath areolar region were smaller those outside areola. Finding of cancer cells or suspicious cancer cells through cytologic examination of nipple discharge smear and breast mass puncture usually had important significance. In addition, near infrared ray scanning shows high rate of correct diagnosis; estimation of carcinoembryonic autigen(CEA) in nipple discharge is beneficial to the early diagnosis of malignant diseases.