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Biomedical subjects

Y C Tung

Publications and source records attributed to Y C Tung.

At least 19 recordsLinked to original sources
PubMed2001

Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer disease brain and in okadaic acid-treated SY5Y cells.

We investigated the role of neurofilament (NF) proteins in Alzheimer disease (AD) neurofibrillary degeneration. The levels and degree of phosphorylation of NF proteins in AD neocortex were determined by Western blots developed with a panel of phosphorylation-dependent NF antibodies. Levels of all three NF subunits and the degree of phosphorylation of NF-H and NF-M were significantly increased in AD as compared to Huntington disease brains used as control tissue. The increase in the levels of NF-H and NF-M was 1.7- and 1.5-fold (P<0.01) as determined by monoclonal antibody SMI33, and was 1.6-fold (P<0.01) in NF-L using antibody NR4. The phosphorylation of NF-H and NF-M in AD was increased respectively at the SMI31 epitope by 1.6- and 1.9-fold (P<0.05) and at the SMI33 epitope by 2.7- and 1.3-fold (P<0.01 and P<0.05). Essentially similar effects were observed in SY5Y human neuroblastoma cells when treated with okadaic acid, an inhibitor of protein phosphatase (PP)-2A and -1. This is the first biochemical evidence which unambiguously demonstrates the hyperphosphorylation and the accumulation of NF subunits in AD brain, and shows that the inhibition of PP-2A/PP-1 activities can lead to the hyperphosphorylation of NF-H and NF-M subunits.

Aged↗
PubMed2001

Differential effects of alpha-, beta- and gamma(2)-melanocyte-stimulating hormones on hypothalamic neuronal activation and feeding in the fasted rat.

Hypothalamic pro-opiomelanocortin neurones have an established role in the control of feeding. While pro-opiomelanocortin is the precursor for at least three melanocortin peptides, alpha-, beta- and gamma-melanocyte-stimulating hormone (MSH), it has been widely assumed that alpha-MSH is the predominant ligand involved. We compared the effects of centrally administered alpha-, beta- and gamma(2)-MSH on hypothalamic neuronal activation and on food intake in rats fasted for 48 h. Significant reductions in food intake were seen with alpha-MSH (first hour) and gamma(2)-MSH (second hour) but not with beta-MSH. The pattern of neuronal activation, assessed by the detection of early growth response factor-1 protein, showed considerable overlap; all three melanocortins activated cells in the arcuate, ventromedial, paraventricular, periventricular and supraoptic nuclei, as well as the preoptic area. alpha-MSH and beta-MSH produced activation in the dorsomedial nuclei while gamma(2)-MSH was only weakly active here. Retrograde labelling by systemic Fluorogold injection revealed that many cells activated by MSH compounds in the arcuate, paraventricular, periventricular and supraoptic nuclei (but not dorsomedial or ventromedial) project outside the blood-brain barrier and are therefore likely to include neuroendocrine cells. Desacetyl-alpha-MSH, which has previously been reported to lack effects on feeding, produced no discernible neuronal activation in the hypothalamus. Our finding that both the pattern of neuronal activation and the distribution of neuroendocrine cells activated in response to these closely related peptides show only partial overlap suggests that, in addition to common pathways, there may exist distinct hypothalamic circuits activated by different pro-opiomelanocortin products. The slower time course of gamma(2)-MSH- versus alpha-MSH-induced suppression of feeding provides further support for the notion that the biological responses to individual melanocortin peptides may involve distinct neuronal mechanisms.

Animals↗
PubMed2001

Actions of leptin on growth hormone secretagogue-responsive neurones in the rat hypothalamic arcuate nucleus recorded in vitro.

In the arcuate nucleus, the growth hormone (GH) secretagogue (GHS)-responsive cells include a subpopulation of the neuropeptide Y (NPY) neurones. It is not known whether these include the orexigenic NPY population that are inhibited by the satiety hormone, leptin. Thus we investigated whether (i) the arcuate nucleus cells electrically excited by GHS are inhibited by leptin and (ii) chronic central leptin infusion alters GHS-induced Fos expression. Of 36 cells recorded from a trimmed hypothalamic slice containing arcuate nucleus, 13 cells were excited by the nonpeptide GHS, CP-459,599. The predominant response of these cells to leptin was inhibitory: six inhibited, three excited and four unresponsive. Similar responses were observed in a population of arcuate cells recorded from a preparation in which synaptic transmission was blocked, suggesting that leptin acts directly on a subpopulation of GHS-responsive neurones. Intracerebroventricular infusion of leptin for 1 week did not alter the number of cells expressing Fos following GHS administration. Thus, while leptin does not appear to influence the central actions of GHS to induce immediate early gene expression, it does act directly on a subpopulation of cells excited by GHS, eliciting mostly inhibitory but also some excitatory responses. It will be interesting to discover the consequences of leptin's inhibitory effects on the hypothalamic circuits excited by GHS, particularly since leptin paradoxically has a stimulatory effect on GH secretion, presumed to reflect a suppression of central NPY pathways.

Animals↗
PubMed2001

Inverted follicular keratosis.

Inverted follicular keratosis (IFK) is a benign skin lesion that typically presents as an asymptomatic, solitary nodule on the face of middle-aged and older individuals. IFK may mimic malignant lesions, especially squamous cell carcinoma (SCC), both clinically and pathologically. We report a 35-year-old male patient who had an exophytic nodule with papillary surface on his right nasal ala of 3 months' duration. The nodule was solitary, flesh colored, 5 mm in diameter and tended to bleed. The patient received shave excision with cautery under the clinical impression of pyogenic granuloma. Pathologically, diagnostic confusion existed between IFK and SCC. Squamous eddy formation and lack of epithelial dysplasia were suggestive of IFK. The tissue was investigated for the presence of human papillomavirus (HPV) DNA sequences by polymerase chain reaction (PCR) and negative result was obtained. This patient healed satisfactorily after removal of the lesion and no visible recurrence occurred during the following 10 months. The possibility of histologically confusing IFK with SCC, leading to unwarranted disfiguring treatments of a benign lesion, is emphasized.

Adult↗
PubMed2001

Lipid myopathy associated with renal tubular acidosis and spastic diplegia in two brothers.

Lipid myopathy is a group of disorders involving mitochondrial fatty acid oxidation. We describe two brothers, 3 years 8 months old and 2 years 9 months old, respectively, with progressive spastic diplegia, developmental delay, failure to thrive, and chronic metabolic acidosis who had lipid myopathy and renal tubular acidosis. Brain magnetic resonance imaging revealed demyelinating changes in the periventricular white matter, which was compatible with spastic diplegia. These symptoms may be related to errors in fatty acid metabolism. Cerebral palsy had been misdiagnosed in both of these patients at another hospital. Therefore, for patients with late-onset and progressive spastic diplegia, detailed investigations for underlying diseases are warranted.

Acidosis, Renal Tubular↗
PubMed2000

Antiepiligrin cicatricial pemphigoid.

Cicatricial pemphigoid is a chronic subepithelial autoimmune blistering disease of mucous membranes and skin. Recently, a subtype of cicatricial pemphigoid with autoantibodies to epiligrin was identified. We describe a Taiwanese patient who presented with ocular, oral, and cutaneous involvement. Direct immunofluorescence showed IgG and C3 deposition in epidermal basement membrane; indirect immunofluorescence showed circulating IgG autoantibodies reactive with the dermal side of 1 mol/L sodium chloride-split skin. Immunoblotting of laminin 5 isolated from the extracellular matrix of cultured human keratinocytes showed no specific reactivity. In contrast, with immunoprecipitation of the conditioned culture media from biosynthetically radiolabeled human keratinocytes, this patient's serum clearly reacted with a series of disulfide-linked polypeptides that correspond to laminin 5(alpha3beta3gamma2) and laminin 6(alpha3beta1gamma1). This is the first confirmed case of a patient of Chinese ancestry with this disease entity.

Aged↗
PubMed2000

Urinary tract infection in febrile infants younger than eight weeks of Age.

OBJECTIVE: To assess the usefulness of laboratory parameters, including peripheral white blood cell (WBC) count, C-reactive protein (CRP) concentration, erythrocyte sedimentation rate (ESR), and microscopic urinalysis (UA), for identifying febrile infants younger than 8 weeks of age at risk for urinary tract infection (UTI), and comparison of standard UA and hemocytometer WBC counts for predicting the presence of UTI. METHODS: A total of 162 febrile children <8 weeks of age were enrolled in this prospective study. All underwent clinical evaluation and laboratory investigation, including WBC count and differential; ESR; CRP; blood culture; a lumbar puncture for cell count and differential, glucose level, protein level, Gram stain, and culture; and a UA and urine culture. All urine specimens were obtained by suprapubic aspiration and microscopically analyzed with standard UA as well as with hemocytometer WBC counts. Quantitative urine cultures were performed. Sensitivity, specificity, accuracy, likelihood ratios, and receiver operating characteristic (ROC) curves were determined for each of the screening tests. RESULTS: There were 22 positive urine culture results of at least 100 colony-forming unit/mL. Eighteen of these 22 patients were males, and all were uncircumcised. There were significant differences for pyuria >/=5 WBCs/hpf, pyuria >/=10 WBC/microL, CRP >20 mg/L, and ESR >30 mm/hour between culture-positive and culture-negative groups (P <.05). The ROC area for hemocytometer WBC count, standard UA, peripheral WBC count, ESR, and CRP concentration were.909 +/-.045,.791 +/-.065,.544 +/-.074,. 787 +/-.060, and.822 +/-.036, respectively. The ROC curve analysis indicates that the CRP, ESR, and standard UA were powerful but imperfect tools with which to discriminate for UTI in potentially infected neonates. Hemocytometer WBC counts had the highest sensitivity, specificity, accuracy, and likelihood ratios for identifying very young infants with positive urine culture results. For all assessments, hemocytometer WBC counts were significantly different, compared with the standard urinalysis. ESR, CRP, and peripheral WBC counts were not helpful in identifying UTI in febrile infants. CONCLUSION: UTI had a prevalence of 13.6% in febrile infants <8 weeks of age. The CRP, ESR, and standard UA were imperfect tools in discriminating for UTI, and the sensitivity of these laboratory parameters was relatively low. Hemocytometer WBC count was a significantly better predictor of UTI in febrile infants.

Female↗
PubMed1999

Detection of human papilloma virus and Epstein-Barr virus DNA in nasopharyngeal carcinoma by polymerase chain reaction.

Nasopharyngeal carcinoma (NPC) is an unique epithelial malignancy which occurs at a high frequency in certain regions of Southeast Asia. Human papilloma virus (HPV) and Epstein-Barr virus (EBV) have both been identified in tissue specimens from NPC. Nevertheless, the association between viral infection and NPC remains unclear. The purpose of this study was to demonstrate that simultaneous infection with EBV and HPV can occur in NPC. Eighty-eight fresh tissue samples which contained sufficient and adequate DNA from patients with histologically confirmed NPC were examined for the existence of HPV and EBV DNA by polymerase chain reaction (PCR). The results showed that HPV and EBV DNA were detected in 51% and in 83% of the specimens, respectively. Coexistence of EBV and HPV in NPC was found in 42% of the samples. The "high risk" types including HPV-16 and HPV-18 accounted for 67% of 45 HPV positive samples. Furthermore, 80% of HPV-16 or HPV-18 positive samples also contained EBV DNA. Our findings suggest that coexistence of EBV and "high risk" HPV-16 or HPV-18 infection may be an important factor in the pathogenesis of NPC.

DNA, Viral↗
PubMed1997

Distribution, levels, and activity of glycogen synthase kinase-3 in the Alzheimer disease brain.

A number of studies have implicated a proline-directed protein kinase, glycogen synthase kinase-3 (GSK-3) in the hyperphosphorylation of tau in Alzheimer's disease (AD). Toward understanding the role of GSK-3 in the abnormal hyperphosphorylation of tau in AD we have found that GSK-3 is prominently present in neuronal cell bodies and their processes and co-localizes with neurofibrillary changes in AD brain. Furthermore, the levels of GSK-3 as determined by indirect ELISA are approximately 50% increased in the postsynaptosomal supernatant from AD brains as compared to the controls. However, no increase in GSK-3 enzyme activity was detected. In AD brain, with its reduced phosphatase activity, even normal levels of GSK-3 activity might be sufficient for the hyperphosphorylation of tau.

Alzheimer Disease↗
PubMed1995

Comparison of the genetic variation in type 1 dengue virus isolates in Taiwan, 1987-1992.

In this study, the genetic variation of eight dengue-1 strains isolated in Taiwan from 1987 to 1992 (including two imported strains) were studied. A fragment of 490 nucleotides from the E/NS1 junction was amplified and studied by reverse transcription-polymerase chain reaction (RT-PCR) and vector cloning. By comparing the nucleotide sequences of these strains, it was found that local strains in Taiwan shared geographic similarity. The nucleotide differences among local strains were less (0.61% to 2.24%) than the differences between imported strains and other strains (2.04% to 4.29%). The differences of nucleotide sequences between local strains and the prototype remain constant (5.10%-5.29%). However, the differences in nucleotide sequences between imported strains and the prototype ranged from 3.89% to 7.14%. Since the point mutations occurred in the wobble position of the codon, only conserved changes resulted in the amino acid among the isolates.

Amino Acids↗
PubMed1994

Rabbit IgG cross-reacts with Alzheimer neurofibrillary tangles.

Biochemical studies have demonstrated that the paired helical filaments (PHF) of Alzheimer neurofibrillary tangles are mostly made up of tau and to a lesser degree of ubiquitin and other proteins. In addition, immunocytochemical labeling of tangles with antibodies to various other neuronal proteins has been shown previously. We report here the labeling of the locations of PHF, i.e., Alzheimer neurofibrillary tangles, neuropil threads and plaque neurites in tissue sections with a goat antiserum to rabbit IgG (GAR-T). The labeling is comparable in strength and distribution to that of tau and ubiquitin antibodies. The PHF-staining antibodies could be removed by absorption with native rabbit IgG but not with human IgG, IgG-depleted rabbit serum, rabbit IgG heavy chains or light chains eluted from nitrocellulose membranes. Furthermore, the PHF reactivity was obliterated by absorption with brain homogenate and a fraction enriched in soluble abnormally phosphorylated tau, but not with purified bovine tau or SDS-washed preparations of the relatively insoluble population of PHF. On immunoblots of both normal human tau and Alzheimer abnormally phosphorylated tau-enriched preparations, GAR-T labeled a set of three to five polypeptides in the tau region. Some of these polypeptides co-migrated with the tau bands. These results indicate (i) that PHF in Alzheimer's disease brain cross-react with a structural epitope/s present on native rabbit IgG, and (ii) that the cross-reactivity with PHF is probably due to tau.

Aged↗
PubMed1993

Microtubule-associated protein tau. Abnormal phosphorylation of a non-paired helical filament pool in Alzheimer disease.

The major protein subunit of the paired helical filaments (PHF) of Alzheimer disease (AD) is the microtubule-associated protein tau. Tau is a family of phosphopolypeptides that are abnormally phosphorylated in PHF. In this study, a non-PHF pool of tau abnormally phosphorylated at Ser-199/202, and tau not phosphorylated at this site (AD P-tau and AD tau, respectively) were isolated from the 27,000 x g to 200,000 x g fraction of AD brain homogenate by extraction in 8 M urea, followed by dialysis against Tris buffer. AD P-tau and AD tau were further purified and separated from each other by acid precipitation, glial fibrillary acidic protein affinity chromatography, and phosphocellulose chromatography. The resulting AD P-tau and AD tau preparations were free of cytoskeletal proteins, ubiquitin, and beta-amyloid peptide. Immunochemical and morphological analysis of AD P-tau preparations revealed that most of the protein was of non-PHF origin. The AD P-tau was about 3-4-fold (approximately 8 mol P04/mol protein, M(r) 41,318) more phosphorylated than cytosolic tau from AD and control brains. Unlike PHF, the AD P-tau lacked ubiquitin. In AD brain the levels of cytosolic tau were about half of those in control aged cases. These findings suggest that the abnormal phosphorylation of tau in AD occurs in the cytosol.

Aged↗
PubMed1990

Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia.

A strong immunoreactivity for ferritin was observed in the neuritic (senile) plaques in Alzheimer's disease hippocampus. The ferritin accumulation was almost exclusively associated with the microglia, which appeared to have proliferated greatly. These cells were also positive for HLA-DR, a putative marker for reactive microglia. In contrast, in the diffuse plaques, which were without neuritic pathology, the ferritin-stained microglia appeared to be normal. Microglia were seen frequently in contact with neurons undergoing neurofibrillary changes but only the tangles in the extracellular space were ferritin positive. No ferritin was detected, by Western blots, in paired helical filaments isolated from Alzheimer's disease brain, suggesting that ferritin was most likely weakly associated with and was not a constituent of these fibrils. No correlation between increased ferritin/microglia activity and blood-brain barrier leakage was detected. Ferritin, an iron-storage protein, might have a role in the formation of amyloid through the action of free radicals generated during the release of iron from the ferritin molecule. Alternatively, the ferritin/microglia system might be secondarily involved in the removal and processing of the amyloid.

Aged↗
PubMed1989

Identification and localization of a tau peptide to paired helical filaments of Alzheimer disease.

Amino acid sequencing of a CNBr digest of the tau protein isolated from bovine brain revealed an amino acid sequence of 17 residues, Pro-Gly-Leu-Lys-Glu-Ser-Pro-Leu-Gln-Ile-Gly-Ala-Ala-Pro-Gly-Leu-Lys, which we call peptide I, with heterogeneity at position 11 of glycine (peptide Ia) and proline (peptide Ib); peptide I showed no homology with the previously reported cDNA-derived mouse and human tau sequences. Antisera raised to synthetic peptides corresponding to peptides Ia and Ib labeled all the bovine tau polypeptides recognized by other monoclonal and polyclonal antibodies to bovine tau. Antisera to peptide Ib did not label any mouse tau polypeptides; however, an anti-Ia antiserum labeled two of the four mouse tau polypeptides. Antisera to both peptides labeled paired helical filaments (PHF) as neurofibrillary tangles, plaque neurites, and neuropil threads in Alzheimer disease brain and PHF polypeptides on immunoblots. Immunostaining with anti-Ia antisera of PHF in tissue sections and PHF polypeptides, but not bovine tau, on immunoblots was markedly increased when pretreated with alkaline phosphatase. These studies suggest that (i) the amino acid sequences of some isoforms of tau peptide might be different from that predicted from cDNAs, (ii) a tau peptide that is absent in the predicted sequences is present in PHF in Alzheimer disease, and (iii) tau in PHF is abnormally phosphorylated.

Alzheimer Disease↗
PubMed1989

Amyloid protein and neurofibrillary tangles coexist in the same neuron in Alzheimer disease.

In Alzheimer disease, paired helical filaments accumulate in the neuron, and amyloid fibers are found in the extracellular space in the neuropil and brain vessels. Amyloid and paired helical filaments are morphologically distinct. Although messenger RNA that encodes the amyloid has also been shown in several tissues, including brain, the intracellular expression of the protein has not been observed. By using monoclonal antibodies to a synthetic amyloid beta peptide, the present study demonstrates that amyloid reactivity is present in both Alzheimer patients and normal individuals in different types of neurons, including the neurons with the neurofibrillary tangles, but not in the tangle itself.

Alzheimer Disease↗
PubMed1988

Microtubule-associated polypeptides tau are altered in Alzheimer paired helical filaments.

Antisera were raised in rabbits to purified bovine tau and to isolated Alzheimer paired helical filaments (PHF) washed with sodium dodecyl sulfate (SDS). Both anti-tau and anti-PHF sera labeled at electron microscopic level PHF which had been isolated either by extraction with SDS or treatment with crude collagenase. On immunoblots all anti-tau and anti-PHF sera labeled bovine brain tau as well as the major 45- to 62-kDa PHF polypeptides which had been previously shown to co-migrate on SDS gels with normal human tau (J. Biol. Chem., 261 (1986) 6084-6089). All antisera labeled Alzheimer neurofibrillary tangles on tissue sections and the PHF polypeptides on immunoblots. Pretreatment with alkaline phosphatase had no effect on the immunostaining. The antisera did not react with ubiquitin, neurofilament triplet polypeptides and with the exception of one antiserum with tubulin and high-molecular weight microtubule-associated proteins. Absorption of tau antisera with tau and PHF and of PHF antisera with PHF resulted in complete removal of the tangles-staining antibodies. In case of the anti-PHF sera when adsorbed with tau, only the staining of a certain tangles population, the dense type, was eliminated and that too at more than 20 times the amount needed for the anti-tau sera; the staining of the loosely packed type of tangles, presumably the final stage, gradually decreased but was not completely abolished. On immunoblots the tau-like major PHF bands remained labeled by the tau-absorbed anti-PHF sera.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1988

Immunomodulation by a unicellular green algae (Chlorella pyrenoidosa) in tumor-bearing mice.

A unicellular algae, Chlorella pyrenoidosa, was used as a biological response modifier. In C57BL/6(B6), C3H/He and DDD/1 mice, both intraperitoneal or oral administrations of autoclaved Chlorella cells or heat-extracted substance were carried out every other day for 10 days before mouse mammary carcinoma (MM-2) or Ehrlich ascites cells were transplanted into the peritoneal cavity. In case of mouse leukemia cells (EL-4), subcutaneous transplantation was carried out. All control mice died within 20 days after each tumor cell transplantation, while 73.3-80% of the treated groups survived over 60 days in the combination of MM-2 vs. C3H/He and EL-4 vs. B6, respectively. The cytotoxic activities against tumor cells, that were abolished by treatment with anti-Thyl.2 monoclonal antibody plus complement, were evidenced in the experimental host. Since Chlorella cells and derivatives showed no indication of direct in vitro cytotoxicity to either tumor or mouse spleen cells, the antitumor effects documented may be mediated by host immune response.

Adjuvants, Immunologic↗