Biomedical subjects

J H Su

Publications and source records attributed to J H Su.

At least 37 records · Page 2Linked to original sources

PubMed1998

Cloning and sequence analysis of the Candida tropicalis URA3 gene encoding orotidine-5'-phosphate decarboxylase.

An integrative transformation system was established for a phenol-utilizing strain of Candida tropicalis M4. The system is based on an auxotrophic mutant host of C. tropicalis U-6 that is defective in orotidine-5'-phosphate decarboxylase (ODCase). As a selectable marker, we isolated and characterized the C. tropicalis URA3 gene, which codes for ODCase. The gene was cloned by complementation of the ura3 mutation of Sachharomyces cerevisiae SHY-3 and the pyrF mutation of Escherichia coli. The C. tropicalis U-6 was transformed by plasmid containing the C. tropicalis URA3 gene at a frequency of 1 to 10 transformants per microgram of plasmid DNA. When the URA3 gene was expressed in E. coli minicells, a 30-kDa protein was identified. Nucleotide sequence analysis revealed the presence of an open reading frame, encoding a protein of 268 amino acids with a calculated molecular mass of 29.7 kDa. The nucleotide sequence of URA3 gene and its deduced amino acid sequence showed significant homology to those of the ODCase of other fungal species.

Base Sequence↗

PubMed1998

Plaque biogenesis in brain aging and Alzheimer's disease. II. Progressive transformation and developmental sequence of dystrophic neurites.

Plaque-associated dystrophic neurites are a common pathological feature in the brains of patients with Alzheimer's disease (AD). In the present study, we investigated the relative abundance and progressive transformation of the amyloid precursor protein (APP), neurofilament (NF) and paired helical filament (PHF) tau-positive dystrophic neurites, within plaques in non-demented controls versus plaque-associated dystrophic neurites in mild or severe AD using double and triple immunolabeling. We also determined the argentophilia of the various sub-populations of dystrophic neurites. In aged non-demented brain, approximately half of the APP-positive plaques contained NF-immunopositive dystrophic neurites; rarely were PHF/tau-positive dystrophic neurites detectable. In contrast, in the AD brain, three-fourths of the APP-positive plaques contained NF-positive dystrophic neurites and half contained PHF/tau neurites. We also observed focal patches of hyper-phosphorylated NF and/or PHF/tau within APP-immunopositive dystrophic neurites, which appeared similar to retrograde degeneration, whereas we never observed focal accumulations of APP within NF- or PHF/tau-positive fibers. We hypothesize that plaque-associated dystrophic neurites within plaques develop in a particular sequence: APP-positive dystrophic neurites appear first and are non-argentophilic. This is followed by the appearance of NF-positive dystrophic neurites, where a subset of NF-positive dystrophic neurites are lightly argentophilic. Over time, PHF/tau-positive dystrophic neurites develop and are strongly argentophilic. These data suggest that dystrophic neurites can develop retrogradely from focal plaque damage to induce somatic and dendritic degeneration and potentially contribute to neurofibrillary tangle formation.

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PubMed1998

Hysteroscopic resection of vaginal septum in an adolescent virgin with obstructed hemivagina.

This article reports on one patient with a double uterus, unilateral vaginal obstruction, with hemi-haematocolpos and ipsilateral renal agenesis. Early accurate diagnosis followed by the excision of the obstructing vaginal septum offers complete relief of symptoms, while preserving reproductive capacity. Unlike conventional excision of vaginal septum, we used resectoscope excision with cutting electrode under continuous pure distilled water irrigation. The postoperative course was uneventful, and haematocolpos and severe dysmenorrhoea disappeared. The resected vaginal area revealed re-epithelialization by hysteroscope follow-up one year after resection. With advancements in resectoscopic operation, evaluation and treatment of vaginal disorders in babies and virgins is very feasible.

Child↗

PubMed1997

Neuronal DNA damage precedes tangle formation and is associated with up-regulation of nitrotyrosine in Alzheimer's disease brain.

The relationship of neuronal DNA damage to tangle-bearing neurons and nitrotyrosine (NT) expression, a neurochemical marker of oxidative damage mediated by peroxynitrite, was examined in visual cortex of AD patients. Many terminal deoxynucleotidyl transferase (TdT)-positive neurons were detected and the majority (93%) of these TdT-labeled neurons lacked evidence of tangle formation. NT expression was elevated in AD cases and most TdT-labeled nuclei also showed strong NT immunoreactivity. These data suggest the hypothesis that the neurons with DNA damage in the absence of tangle formation may degenerate by tangle-independent mechanisms and that oxidative damage may contribute to such mechanisms in AD.

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PubMed1997

Transneuronal degeneration in the spread of Alzheimer's disease pathology: immunohistochemical evidence for the transmission of tau hyperphosphorylation.

Neurofibrillary tangles and dystrophic neurites appear to develop in a highly characteristic spatial and temporal sequence in AD. In order to examine the nature of the cellular progression we have studied the trisynaptic entorhinal, dentate gyrus, CA3/4 circuit, using an antibody to hyperphosphorylated tau which is a biochemical marker for tangle formation. In early AD cases, we found numerous ATB-stained boutons in the outer molecular layer of the dentate gyrus, the termination field of neurons from the entorhinal cortex. These AT8-stained boutons co-labeled with synaptophysin, indicating that they represent synaptic boutons in an early state of degeneration. Since the labeled boutons were apposed to or clustered around dendrites or soma that lacked or had less intense staining for AT8 or PHF-1, it appeared that presynaptic events preceded postsynaptic neurofibrillary tangle formation. Furthermore, as a function of disease progression, the pattern of degeneration moved through the circuit. In this progression tau, which is normally localized to axons, becomes redistributed into dendrites and hyperphosphorylated. These observations support the hypothesis that the presynaptic terminal changes may promote the formation of initial neurofibrillary pathology in the postsynaptic neurons via anterograde transneuronal mechanisms and that this initiates a breakdown of routing and sorting mechanisms for the cytoskeletal protein tau.

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PubMed1997

Clinicopathological features of bladder cancer associated with chronic exposure to arsenic.

A high incidence of bladder cancer has been documented in an area of chronic arsenic (As) exposure. This study investigates the characteristics of As-associated (n = 49) and other (n = 64) bladder cancers. A higher histological grading was observed for the As-exposed tumours (P = 0.04), but no other difference in pathobiological features or prognosis was found between the two groups.

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PubMed1997

Bax protein expression is increased in Alzheimer's brain: correlations with DNA damage, Bcl-2 expression, and brain pathology.

We have shown that many neurons in Alzheimer's disease (AD) exhibit terminal deoxynucleotidyl transferase (TdT) labeling for DNA strand breaks, and upregulation of Bcl-2 is associated with neurons exhibiting nuclear DNA fragmentation, while downregulation of Bcl-2 is associated with tangle-bearing neurons in AD brains. Consequently, we examined the expression of bcl-associated X (Bax) protein in AD brain. Immunoreactivity for Bax was seen in neurons and microglia of the hippocampal formation, and was elevated in the majority of AD cases as compared to control cases. Interestingly, 3 transitional cases, which had mild degeneration changes, exhibited relatively high levels of Bax immunoreactivity. Most Bax-positive neurons showed either TdT-labeled nuclei or Bcl-2 immunoreactivity. Although Bax immunoreactivity was detected within most early tangle-bearing neurons, many Bax-positive neurons did not colocalize with later-stage tangle-bearing neurons. In regions containing relatively few tangles in mild AD brains, many TdT-labeled neurons were immunolabeled with Bax antibody and most of them lacked evidence of neurofibrillary changes. These findings suggest that Bax may contribute to neuronal cell death in AD. Furthermore, DNA damage and the upregulation of Bax appear to precede tangle formation or may represent an alternative pathway of cell death in AD.

Aged↗

PubMed1997

Cloning and sequence analysis of a novel hemolysin gene (vllY) from Vibrio vulnificus.

A gene (vllY) encoding a novel hemolysin of Vibrio vulnificus CKM-1 has been cloned and sequenced. When the vllY gene was expressed in minicells, a unique peptide of approximately 40 kDa was identified. Subcellular fractionation of Escherichia coli cells carrying the vllY gene indicated that the VllY protein was distributed in both the cytoplasmic and the periplasmic fractions, with the notable ability to appear in the latter compartment. Nucleotide sequence analysis predicted a single open reading frame of 1,071 bp encoding a 357-amino acid polypeptide with an estimated pI of 5.02. The deduced amino acid sequence of VllY showed high similarity to the sequence of legiolysin, responsible for hemolysis, pigment production, and fluorescence in Legionella pneumophila. The enzyme also exhibited sequence homology to the MelA protein sequence of Shewanella colwelliana and the sequences of 4-hydroxyphenylpyruvate dioxygenase family proteins from various organisms. PCR screening and Southern blotting of V. vulnificus strains revealed that all of the 41 V. vulnificus clinical isolates contained vllY-like genes.

Amino Acid Sequence↗

PubMed1996

Plaque biogenesis in brain aging and Alzheimer's disease. I. Progressive changes in phosphorylation states of paired helical filaments and neurofilaments.

Paired helical filament (PHF)/tau immunoreactive dystrophic neurites are a common pathological feature in the brain of patients with Alzheimer's disease. Recent studies suggest that swollen neurofilament-immunoreactive neurites are also present in senile plaques. In the present study, we investigated whether PHF/tau-positive dystrophic neurites are located in all subtypes of plaques and whether swollen neurofilament-immunoreactive neurites are hyper-phosphorylated, using a battery of antibodies to PHF/tau, neurofilament, and beta-amyloid protein. PHF/tau-positive dystrophic neurites were present in and around nearly all subtypes of plaques, including small amyloid deposits, diffuse plaques, and perivascular plaques in the hippocampal formation of Alzheimer brain. The earlier changes were detectable with AT8 antibody and later changes with PHF-1 antibody. Plaque-associated PHF/tau-positive dystrophic neurites were rare or absent in the hippocampal formation of normal aged brain. Swollen neurofilament-positive neurites appeared to be hyper-phosphorylated in Alzheimer's disease and to a lesser degree in aged control brains. Neurites that contained hyper-phosphorylated tau as well as neurofilament were strongly argentophilic because both populations of dystrophic neurites stained with silver stains. Swollen neurofilament-positive plaque-associated neurites were often present in the absence of PHF/tau-positive plaque-associated dystrophic neurites. These data suggest that PHF/tau-positive dystrophic neurites are a common component of all subtypes of plaques in Alzheimer brain and neurofilament protein in swollen neurites, like tau protein, is hyper-phosphorylated. Hyper-phosphorylated neurofilaments in plaque-associated neurites may represent one of the earliest cytoskeletal changes in vulnerable neurons in Alzheimer's disease and aged control brains.

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PubMed1996

Gene expression of Alzheimer-associated presenilin-2 in the frontal cortex of Alzheimer and aged control brain.

The presenilin-2 (PS2) gene expression pattern in Alzheimer's disease (AD) and control brains was examined using nonradioactive in situ hybridization. Message for PS2 was primarily detectable in neurons, particularly in somal cytoplasm. Intense staining signal was most commonly found in large pyramidal neurons, whereas moderate or faint staining was usually present in smaller neurons. The pattern of PS2 gene expression exhibited a laminar distribution profile in the frontal cortex. A small subset of tangle-bearing neurons exhibited PS2 hybridization signal in AD. PS2 mRNA expression appeared correlated to a high degree with lipofuscin autofluorescence in a large subset of neurons.

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PubMed1996

DNA damage and apoptosis in Alzheimer's disease: colocalization with c-Jun immunoreactivity, relationship to brain area, and effect of postmortem delay.

Many neurons in Alzheimer's disease (AD) exhibit terminal deoxynucleotidyl transferase (TdT) labeling for DNA strand breaks with a distribution suggestive of apoptosis. We have shown previously that immunoreactivity for c-Jun is elevated in AD and found in association with neuronal pathology. In addition, cultured neurons undergoing beta-amyloid-mediated apoptosis exhibit a selective and prolonged induction of c-Jun. Consequently, we conducted double-labeling experiments to examine whether c-Jun is associated with DNA strand breaks in AD tissue; we observed a strong colocalization between these markers. As would be predicted based on the distribution of AD pathology, we also found that TdT labeling was prominent in the entorhinal cortex, but absent or at very low levels in cerebellum. Furthermore, we confirmed that postmortem delay (PMD) does not affect TdT labeling within the limits used for tissue used in this study. However, in contrast to previous studies, we report an increase in TdT labeling with more extended PMDs. Finally, gel electrophoresis of genomic DNA isolated from AD and control cases failed to reveal evidence for either an apoptotic or a necrotic mechanism of cell death in AD, possibly because of a low number of cells actually undergoing cell death at any given time. Our findings support the hypothesis that DNA damage labeled using TdT reflects neuronal vulnerability and cell loss associated with AD pathology, and that at least a portion of the cells labeled with this technique is undergoing apoptosis. Furthermore, in agreement with in vitro findings, these results suggest a relationship between the expression of c-Jun and neuronal risk and/or cell death in AD.

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PubMed1996

Up-regulation of Bcl-2 is associated with neuronal DNA damage in Alzheimer's disease.

Cell death and neurofibrillary tangle formation are prominent features of Alzheimer's disease (AD). It has been suggested that DNA damage may reflect neuronal vulnerability. In this context, the Ced homologue Bcl-2 is able to repress a number of cell death programs. Recently we found both numerous nuclei exhibiting DNA damage within neurons in the AD brain and increases in Bcl-2 immunoreactivity. In this study, we examined the relationship between Bcl-2 expression and nuclear DNA damage or tangle formation. Nuclei exhibiting DNA damage were associated with an up-regulation of Bcl-2 expression, whereas tangle-bearing neurons were associated with a down-regulation of Bcl-2 expression.

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PubMed1996

Mechanisms of neuronal death in Alzheimer's disease.

Recent data in cell culture has shown that brain neurons are particularly vulnerable to degeneration by apoptosis. Further the inducers that activate the program (e.g. beta-amyloid, oxidatative damage, low energy metabolism) correspond to conditions present in the Alzheimer's disease (AD) brain. This suggests the possibility that apoptosis may be one of the mechanisms contributing to neuronal loss in this disease. Indeed, some neurons in vulnerable regions of the AD brain show evidence of DNA damage, nuclear apoptotic bodies, chromatin condensation, and the induction of select genes characteristic of apoptosis in cell culture and animal models. This suggests the existence of apoptosis in the AD brain, a hypothesis also consistent with evolving research in one of the regulatory functions of the presenilin genes. On the other hand, DNA damage is present in the majority of neurons in vulnerable regions in early and mild cases. In most tissues, cells in fully activated apoptosis degenerate and are removed within hours to days and thus it seems all DNA damage is unlikely to signify terminal apoptosis. The presence of extensive DNA damage suggests an acceleration of damage, faulty repair process, loss of protective mechanisms, or an activation and arrest of aspects of the apoptotic program. DNA damage is unlikely to be an artifact of postmortem delay or agonal state. The existence of protective mechanisms for neurons may exist as these cells are nondividing and essential. In this context it is interesting that Bcl-2 is upregulated in most neurons with DNA damage. Further, at least one DNA repair enzyme is also upregulated. Thus it appears as if neurons are in a struggle between degeneration and repair. As research advances it is critical to reduce the stimuli that cause the neuronal damage and discover the key intervention points to assist neurons in the repair processes.

Alzheimer Disease↗

PubMed1994

Immunohistochemical evidence for apoptosis in Alzheimer's disease.

Recently, in vitro studies conducted in our laboratory and others have suggested that apoptosis may have a role in the neuronal cell death associated with Alzheimer's disease (AD). To evaluate this hypothesis, the hippocampi and entorhinal cortices of AD, aged control, and surgical biopsy tissue were examined using the ApopTag system for the detection of DNA fragmentation and DNA strains to reveal nuclear morphology. Numerous neuronal nuclei displaying distinct morphological characteristics of apoptosis were present within tangle-bearing neurons as well as non-tangle-bearing neurons in AD brain, whereas few or no such nuclei were detected in control brain. Our in vivo results support the hypothesis that apoptosis may be one mechanism leading neuronal cell death in AD.

Aged↗

PubMed1994

Early phosphorylation of tau in Alzheimer's disease occurs at Ser-202 and is preferentially located within neurites.

Within the neurofibrillary tangles (NFTs) and dystrophic neurites (DNs) of Alzheimer's disease (AD), the cytoskeletal protein tau is abnormally hyperphosphorylated. In this study we evaluate the phosphorylation of specific residues on tau within different phases of the formation of NFTs. Two monoclonal antibodies, AT8 and PHF-1, were used to selectively recognize phosphorylated Ser-202 and Ser-396 of PHF-tau protein, respectively. We found that abnormal phosphorylation of tau appears to occur first at Ser-202 in DNs, then at Ser-202 in the soma and finally at Ser-396 in DNs and NFTs. These results suggest that abnormal phosphorylation at Ser-202 of PHF-tau in DNs represents one of the earliest neuropathological changes within the neurites of vulnerable neurons and may have a pivotal role in the initial pathogenesis of AD.

Aged↗

PubMed1994

Subpopulations of dystrophic neurites [correction of neuritis] in Alzheimer's brain with distinct immunocytochemical and argentophilic characteristics.

Using two monoclonal antibodies, tau-1 and PHF-1, and a sequential staining method combining double-labeling immunofluorescence and Bielschowsky silver staining, we have demonstrated the presence of two populations of dystrophic neurites (DNs) with distinct immunocytochemical and argentophilic characteristics. Tau-1 and PHF-1 immunoreactivity were co-localized in many DNs. However, approximately 20% of the DNs were immunoreactive for PHF-1 only. PHF-1 single-labeled DNs were not visible or very weak with Bielschowsky silver stain. Of DNs continuous with neurofibrillary tangles (NFTs), tau-1/PHF-1 double-labeled DNs were continuous with intracellular NFTs only, while PHF-1 single-labeled DNs were continuous with extracellular NFTs only. Furthermore, the population of DNs that cluster around extracellular NFTs is different from those that cluster around or within senile plaques. The combined use of tau-1 and PHF-1 immunocytochemistry may provide a more accurate indication of the number of extracellular DNs and extracellular NFTs, which may aid in the diagnosis of severe and advanced AD cases.

Aged↗

PubMed1994

A comparison of enzyme-linked immunosorbent assay (ELISA) with sperm immobilization test (SIT) in detection of antisperm antibodies in sera of infertile women.

In the present study, an enzyme-linked immunosorbent assay (ELISA) for antisperm antibodies was compared with a traditional standard sperm immobilization test (SIT) in sera from 158 infertile women in order to evaluate their clinical usefulness for various causes of infertility. Ten pregnant and unmarried women were used as the control group. There was a higher incidence rate by ELISA (13.9%) compared with that by SIT (10.1%) after examination of overall samples, although the difference was not statistically significant. The unexplained infertility group exhibited the highest incidence among the various causes of infertility in both of these two methods. Fifteen (93.8%) of 16 patients with positive SIT showed positive reaction in ELISA method, indicating that a close correlation exists between the two methods. The positive predictive value (54.5%) of ELISA was significantly (p < 0.05) lower than that (87.5%) of SIT, as evaluated with the results of postcoital test (PCT) performed at periovulatory phase. This suggests that the ELISA method for antisperm antibodies is less specific than SIT in view of the PCT results. Nevertheless, no fresh sperms are not required for the ELISA examination. Thus, it seems that the ELISA method may provide a convenient and practical means for mass screening in detecting antisperm antibodies in clinical practice.

Agglutination Tests↗

PubMed1993

Identification and distribution of axonal dystrophic neurites in Alzheimer's disease.

Dystrophic neurites (DNs) are one of the neuropathological characteristics of Alzheimer's disease (AD). Previously, it has been suggested that tau-immunoreactive DNs are of dendritic origin and that axonal and dendritic dystrophic neurites are morphologically indistinguishable. In the present study, two monoclonal antibodies, tau-1 and PHF-1, were used to examine sections of the hippocampal formation from AD and normal aged brains. Both antibodies stained dendritic DNs as well as axonal DNs. Axonal DNs were clearly seen in axonal fiber tracts, white matter and hippocampal terminal regions. Axonal DNs arising from neurofibrillary tangles were easily detected in CA3 and CA1. The morphological appearance of axonal DNs varied with the neuron type from which it originated. The most distinctive feature of tau-1 or PHF-1 immunostained axonal DNs was their uneven contour, alternating swollen and shrunken segments and short rod or cone shaped fragments. In contrast, dendritic dystrophic neurites are thicker and more tortuous. It appears that while DNs are both dendritic and axonal in origin, axonal DNs are more prevalent and widespread in the AD brain than previously realized and may represent one of the main pathological lesions in AD.

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