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Biomedical subjects

J Tsai

Publications and source records attributed to J Tsai.

At least 37 records · Page 2Linked to original sources
PubMed2000

Nerve sprouting and sudden cardiac death.

The factors that contribute to the occurrence of sudden cardiac death (SCD) in patients with chronic myocardial infarction (MI) are not entirely clear. The present study tests the hypothesis that augmented sympathetic nerve regeneration (nerve sprouting) increases the probability of ventricular tachycardia (VT), ventricular fibrillation (VF), and SCD in chronic MI. In dogs with MI and complete atrioventricular (AV) block, we induced cardiac sympathetic nerve sprouting by infusing nerve growth factor (NGF) to the left stellate ganglion (experimental group, n=9). Another 6 dogs with MI and complete AV block but without NGF infusion served as controls (n=6). Immunocytochemical staining revealed a greater magnitude of sympathetic nerve sprouting in the experimental group than in the control group. After MI, all dogs showed spontaneous VT that persisted for 5.8+/-2.0 days (phase 1 VT). Spontaneous VT reappeared 13.1+/-6.0 days after surgery (phase 2 VT). The frequency of phase 2 VT was 10-fold higher in the experimental group (2.0+/-2.0/d) than in the control group (0.2+/-0.2/d, P<0.05). Four dogs in the experimental group but none in the control group died suddenly of spontaneous VF. We conclude that MI results in sympathetic nerve sprouting. NGF infusion to the left stellate ganglion in dogs with chronic MI and AV block augments sympathetic nerve sprouting and creates a high-yield model of spontaneous VT, VF, and SCD. The magnitude of sympathetic nerve sprouting may be an important determinant of SCD in chronic MI.

Adrenergic beta-Antagonists↗
PubMed2000

Intraneuronal Abeta42 accumulation in human brain.

Alzheimer's disease (AD) is characterized by the deposition of senile plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are composed of aggregated beta-amyloid (Abeta) 40/42(43) peptides. Evidence implicates a central role for Abeta in the pathophysiology of AD. Mutations in betaAPP and presenilin 1 (PS1) lead to elevated secretion of Abeta, especially the more amyloidogenic Abeta42. Immunohistochemical studies have also emphasized the importance of Abeta42 in initiating plaque pathology. Cell biological studies have demonstrated that Abeta is generated intracellularly. Recently, endogenous Abeta42 staining was demonstrated within cultured neurons by confocal immunofluorescence microscopy and within neurons of PS1 mutant transgenic mice. A central question about the role of Abeta in disease concerns whether extracellular Abeta deposition or intracellular Abeta accumulation initiates the disease process. Here we report that human neurons in AD-vulnerable brain regions specifically accumulate gamma-cleaved Abeta42 and suggest that this intraneuronal Abeta42 immunoreactivity appears to precede both NFT and Abeta plaque deposition. This study suggests that intracellular Abeta42 accumulation is an early event in neuronal dysfunction and that preventing intraneuronal Abeta42 aggregation may be an important therapeutic direction for the treatment of AD.

Adult↗
PubMed2000

PR39, a peptide regulator of angiogenesis.

Although tissue injury and inflammation are considered essential for the induction of angiogenesis, the molecular controls of this cascade are mostly unknown. Here we show that a macrophage-derived peptide, PR39, inhibited the ubiquitin-proteasome-dependent degradation of hypoxia-inducible factor-1alpha protein, resulting in accelerated formation of vascular structures in vitro and increased myocardial vasculature in mice. For the latter, coronary flow studies demonstrated that PR39-induced angiogenesis resulted in the production of functional blood vessels. These findings show that PR39 and related compounds can be used as potent inductors of angiogenesis, and that selective inhibition of hypoxia-inducible factor-1alpha degradation may underlie the mechanism of inflammation-induced angiogenesis.

Animals↗
PubMed2000

Lower cognitive performance of older football players possessing apolipoprotein E epsilon4.

OBJECTIVE: To determine whether the cognitive status of professional football players varies as a function of age and apolipoprotein E (APOE) genotype. METHODS: Fifty-three active players underwent APOE and neuropsychological assessments. Players were grouped according to age (proxy indicator of high/low exposure to contact) and the presence/absence of at least one copy of the epsilon4 allele. Outcome measures were overall cognitive performance and scores in cognitive domains. RESULTS: As a group, older players possessing APOE epsilon4 exhibited significantly lower cognitive test scores than did all other players studied, including non-epsilon4-possessing players and younger epsilon4-carriers. Measures of general cognitive functioning, information-processing speed and accuracy, and attention were related to poorer performance among the epsilon4-carrying players. In an analysis of variance model, the interaction between APOE genotype and age was significant (P = 0.004). As determined using linear regression, age accounted for 34% of the variance in the memory index among APOE epsilon4-possessing players but did not contribute significantly to variance among the non-epsilon4-possessing players. Older APOE epsilon4-carriers were significantly overrepresented among players whose scores indicated possible cognitive impairment, with the criterion of performing two or more standard deviations below the general normal values in a summary index of general cognitive functioning. CONCLUSION: Older professional football players who possessed the APOE epsilon4 allele scored lower on cognitive tests than did players without this allele or less experienced players of any genotype. The cognitive status of professional athletes with repeated exposure to head trauma may therefore be influenced by age, inherited factors such as APOE genotype, and cumulative exposure to contact.

Adult↗
PubMed2000

Aberrant pathways in the late stages of cholesterol biosynthesis in the rat. Origin and metabolic fate of unsaturated sterols relevant to the Smith-Lemli-Opitz syndrome.

Minor aberrant pathways of cholesterol biosynthesis normally produce only trace levels of abnormal sterol metabolites but may assume major importance when an essential biosynthetic step is blocked. Cholesta-5,8-dien-3beta-ol, its Delta(5,7) isomer, and other noncholesterol sterols accumulate in subjects with the Smith-Lemli-Opitz syndrome (SLOS), a severe developmental disorder caused by a defective Delta(7) sterol reductase gene. We have explored the formation and metabolism of unsaturated sterols relevant to SLOS by incubating tritium-labeled Delta(5,8), Delta(6, 8), Delta(6,8(14)), Delta(5,8(14)), and Delta(8) sterols with rat liver preparations. More than 60 different incubations were carried out with washed microsomes or the 10,000 g supernatant under aerobic or anaerobic conditions; some experiments included addition of cofactors, fenpropimorph (a Delta(8);-Delta(7) isomerase inhibitor), and/or AY-9944 (a Delta(7) reductase inhibitor). The tritium-labeled metabolites from each incubation were identified by silver ion high performance liquid chromatography on the basis of their coelution with unlabeled authentic standards, as free sterols and/or acetate derivatives. The Delta(5,8) sterol was converted slowly to cholesterol via the Delta(5,7) sterol, which also slowly isomerized back to the Delta(5,8) sterol. The Delta(6,8) sterol was metabolized rapidly to cholesterol by an oxygen-requiring pathway via the Delta(7,9(11)), Delta(8), Delta(7), and Delta(5,7) sterols as well as by an oxygen-independent route involving initial isomerization to the Delta(5,7) sterol. The Delta(8) sterol was partially metabolized to Delta(5,8), Delta(6,8), Delta(7,9(11)), and Delta(5,7,9(11)) sterols when isomerization to Delta(7) was blocked.The combined results were used to formulate a scheme of normal and aberrant biosynthetic pathways that illuminate the origin and metabolic fate of abnormal sterols observed in SLOS and chondrodysplasia punctata.

Aerobiosis↗
PubMed1999

Distribution of salicylic acid in human stratum corneum following topical application in vivo: a comparison of six different formulations.

Distribution of salicylic acid in human stratum corneum from treatment of six different formulations was assessed by quantitation of drug content in sequentially tape-stripped stratum corneum after a single 2-h dose was applied unoccluded to skin on the ventral forearm of four female subjects. The profile and total amounts of stratum corneum removed in 20 tape-strips varied among different types of formulations. With or without normalization by the total stratum corneum weights removed, the extent of drug delivery to the stratum corneum decreased in the following order: SA (5%) > > SAC (10%), Duofilm (16.7%) > TSSS (2%) > SAO (10%), Salic (2.5%), the percentage in parentheses indicating the salicylic acid concentration in each formulation. The greatest topical bioavailability was observed for the alcoholic solution containing glycerol (SA). The 10% collodion formulation (SAC) was found to deliver an amount of salicylic acid into the stratum corneum 2-fold greater than 10% ointment formulation (SAO). Use of absorption ointment (TSSS) also increased the uptake of salicylic acid into the stratum corneum in comparison with formulations based on simple ointment (SAO) and oil in water (o/w) cream (Salic). The partitioning of salicylic acid from collodion formulations (SAC and Duofilm) appeared to be concentration-independent. The results of this study indicate that topical bioavailability of salicylic acid in the stratum corneum varies substantially among different formulations.

Adhesives↗
PubMed1999

Hierarchy of structure loss in MD simulations of src SH3 domain unfolding.

To complement experimental studies of the src SH3 domain folding, we studied 30 independent, high-temperature, molecular dynamics simulations of src SH3 domain unfolding. These trajectories were observed to differ widely from each other. Thus, rather than analyzing individual trajectories, we sought to identify the recurrent features of the high-temperature unfolding process. The conformations from all simulations were combined and then divided into groups based on the number of native contacts. Average occupancies of each side-chain hydrophobic contact and hydrogen bond in the protein were then determined. In the symmetric funnel limit, the occupancies of all contacts should decrease in concert with the loss in total number of native contacts. If there is a lack of symmetry or hierarchy to the unfolding process, the occupancies of some contacts should decrease more slowly, and others more rapidly. Despite the heterogeneity of the individual trajectories, the ensemble averaging revealed an order to the unfolding process: contacts between the N and C-terminal strands are the first to disappear, whereas contacts within the distal beta-hairpin and a hydrogen-bonding network involving the distal loop beta-turn and the diverging turn persist well after the majority of the native contacts are lost. This hierarchy of events resembles but is somewhat less pronounced than that observed in our experimental studies of the folding of src SH3 domain.

Computer Simulation↗
PubMed1999

The packing density in proteins: standard radii and volumes.

The sizes of atomic groups are a fundamental aspect of protein structure. They are usually expressed in terms of standard sets of radii for atomic groups and of volumes for both these groups and whole residues. Atomic groups, which subsume a heavy-atom and its covalently attached hydrogen atoms into one moiety, are used because the positions of hydrogen atoms in protein structures are generally not known. We have calculated new values for the radii of atomic groups and for the volumes of atomic groups. These values should prove useful in the analysis of protein packing, protein recognition and ligand design. Our radii for atomic groups were derived from intermolecular distance calculations on a large number (approximately 30,000) of crystal structures of small organic compounds that contain the same atomic groups to those found in proteins. Our radii show significant differences to previously reported values. We also use this new radii set to determine the packing efficiency in different regions of the protein interior. This analysis shows that, if the surface water molecules are included in the calculations, the overall packing efficiency throughout the protein interior is high and fairly uniform. However, if the water structure is removed, the packing efficiency in peripheral regions of the protein interior is underestimated, by approximately 3.5 %.

Animals↗
PubMed1999

hnRNP C and polypyrimidine tract-binding protein specifically interact with the pyrimidine-rich region within the 3'NTR of the HCV RNA genome.

Like other members of the Flaviviridae family, the 3' non-translated region (NTR) of the hepatitis C virus (HCV) is believed to function in the initiation and regulation of viral RNA replication by interacting with components of the viral replicase complex. To inves-tigate the possibility that host components may also participate in this process, we used UV cross-linking assays to determine if any cellular proteins could bind specifically to the 3'NTR RNA. We demonstrate the specific interaction of two host proteins with the extensive pyrimidine-rich region within the HCV 3'NTR. One host protein migrates as a doublet with a molecular weight of 57 kDa and is immunoreactive with antisera specific for polypyrimidine tract-binding protein (PTB), and the other protein (35 kDa) is recognized by a monoclonal antibody specific for heterogeneous nuclear ribonucleoprotein C (hnRNP C). These results suggest that recognition of the large pyrimidine-rich region by PTB and hnRNP C may play a role in the initiation and/or regulation of HCV RNA replication.

3' Untranslated Regions↗
PubMed1999

Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides.

The excessive generation and accumulation of 40- and 42-aa beta-amyloid peptides (Abeta40/Abeta42) in selectively vulnerable brain regions is a major neuropathological feature of Alzheimer's disease. Abeta, derived by proteolytic cleavage from the beta-amyloid precursor protein (betaAPP), is normally secreted. However, recent evidence suggests that significant levels of Abeta also may remain inside cells. Here, we have investigated the subcellular compartments within which distinct amyloid species are generated and the compartments from which they are secreted. Three experimental approaches were used: (i) immunofluorescence performed in intact cortical neurons; (ii) sucrose gradient fractionation performed with mouse neuroblastoma cells stably expressing wild-type betaAPP695 (N2a695); and (iii) cell-free reconstitution of Abeta generation and trafficking from N2a695 cells. These studies demonstrate that: (i) Abeta40 (Abeta1-40 plus Abetax-40, where x is an NH2-terminal truncation) is generated exclusively within the trans-Golgi Network (TGN) and packaged into post-TGN secretory vesicles; (ii) Abetax-42 is made and retained within the endoplasmic reticulum in an insoluble state; (iii) Abeta42 (Abeta1-42 plus Abetax-42) is made in the TGN and packaged into secretory vesicles; and (iv) the amyloid peptides formed in the TGN consist of two pools (a soluble population extractable with detergents and a detergent-insoluble form). The identification of the organelles in which distinct forms of Abeta are generated and from which they are secreted should facilitate the identification of the proteolytic enzymes responsible for their formation.

Alzheimer Disease↗
PubMed1999

Outcome study of cholecystectomy during pregnancy.

BACKGROUND: Several anecdotal papers suggest that laparoscopic cholecystectomy can be done safely in pregnant patients, but few patients are reported and other patients such as those who underwent laparoscopic appendectomy are often included. A larger series would help clarify the situation. METHODS: The Connecticut Laparoscopic Cholecystectomy Registry and data from the Connecticut Hospital Association (CHA) were combined to search for all cholecystectomies performed in pregnant patients from 1992 through 1996. Information on outcomes for both mother and infant was obtained through the cooperation of most of the CHA hospitals. RESULTS: Complete data were available for 46 patients, 20 laparoscopic and 26 open cases. The groups were comparable in all demographic respects except for the timing of cholecystectomy, which was performed at a mean of 18.4 +/- 6.7 weeks (range 9 to 32) of gestation for the laparoscopic and 24.8 +/- 4.7 weeks (range 14 to 35) for the open patients (P = 0.01). A maternal-fetal mortality due to intra-abdominal hemorrhage occurred in the laparoscopic group 2 weeks postoperatively. In the open group, a fetal demise occurred at 21 weeks gestation, 5 weeks postcholecystectomy. The open patients experienced 8 episodes of premature contractions compared with one one such event in the laparoscopic group (P = 0.057). CONCLUSIONS: This represents the largest reported series of laparoscopic cholecystectomy in pregnant patients. Laparoscopic cholecystectomy does not lead to increased numbers of fetal complications. Premature uterine contractions tend to occur more frequently after open cholecystectomy and when the procedure is performed later in gestation.

Adult↗
PubMed1999

Renal abscess: early diagnosis and treatment.

The purpose of this study was to identify initial clinical characteristics that can lead to early diagnosis of renal abscess in the emergency department and predict poor prognosis. A retrospective review of 88 renal abscess patients, from April 1979 through January 1996, was conducted. Patients were categorized into two groups. In group 1, renal abscess was diagnosed by an emergency physician, whereas in group 2 renal abscess was not diagnosed by an emergency physician. Clinical characteristics included demographic data, predisposing medical problems, duration of illness before diagnosis, time spent in hospital diagnosis, initial signs and symptoms, laboratory tests, and radiology studies that may have been useful in the early diagnostic regimes. Clinical factors were also analyzed for their value in predicting poor prognosis. The mean age of 88 patients with renal abscess was 59.8 years. The most common predisposing disorder was diabetes mellitus, followed by renal calculi and ureteral obstruction. The duration of diagnosis by emergency physicians was shorter for group 1 patients (1.2 +/- .4 v group 2, 2.8 +/- 2.9 days; P < .01) and the blood urea nitrogen level was higher in group 1 (55.7 +/- 42.2 mg/dL, v group 2, 33.5 +/- 33.5 mg/dL; P = .02). In the early diagnosis of renal abscess, emergency physicians should focus on patients who have predisposing disorders, ie, diabetes mellitus, renal stones, immunosuppression, longer duration of symptoms of urinary tract infection, and renal failure, who should promptly be investigated with ultrasound in the emergency department. The cure rate after treatment with routine antibiotics plus percutaneous drainage was 64%. This therapy is recommended for initial treatment. Poor prognosis is associated with elderly patients with lethargy and with elevation of the serum blood urea nitrogen level.

Abscess↗
PubMed1999

An Asian-Native American paternal lineage identified by RPS4Y resequencing and by microsatellite haplotyping.

Human paternal population history was studied in 9 populations [three Native American, three Asian, two Caucasian and one African-derived sample(s)] using sequence and short tandem repeat haplotype diversity within the non-pseudoautosegmal region of the Y chromosome. Complete coding and additional flanking sequences (949 base pairs) of the RPS4Y locus were determined in 59 individuals from three of the populations, revealing a nucleotide diversity of 0.0147%, consistent with previous estimates from Y chromosome resequencing studies. One RPS4Y sequence variant, 711C > T, was polymorphic in Asian and Native American populations, but not in African and Caucasian population samples. The RPS4Y 711C > T variant, a second unique sequence variant at DYS287 and nine Y chromosome short tandem repeat (YSTR) loci were used to analyze the evolution of Y chromosome lineages. Three unambiguous lineages were defined in Asian, Native American and Jamaican populations using sequence variants at RPS4Y and DYS287. These lineages were independently supported by the haplotypes defined solely by YSTR alleles, demonstrating the haplotypes constructed from YSTRs can evaluate population diversity, admixture and phylogeny.

Alleles↗
PubMed1999

Novel terpenoid-type quinones isolated from Pycnanthus angolensis of potential utility in the treatment of type 2 diabetes.

Using an ethnomedical-based drug discovery program, two previously unknown compounds (SP-18904 and SP-18905) from Pycnanthus angolensis were isolated that lower glucose concentrations in mouse models of type 2 diabetes. SP-18904 and SP-18905 are terpenoid-type quinones that significantly lowered plasma glucose concentration (p <.05) when given orally to either ob/ob or db/db mice, both of which are hyperglycemic and hyperinsulinemic. The antihyperglycemic actions of SP-18904 and SP-18905 were associated with significant decreases in plasma insulin concentrations (p <.05), suggesting that both compounds lowered glucose by enhancing insulin-mediated glucose uptake. This was supported by the insulin suppression test in ob/ob mice. Studies in hyperglycemic, insulin-deficient mice and in vitro experiments on 3T3-L1 adipocytes further supported this conclusion. As such, these two terpenoid-type quinones represent a new class of compounds of potential use in the treatment of type 2 diabetes.

Adipocytes↗
PubMed1998

Malignant vascular tumors in young patients.

BACKGROUND: To the authors' knowledge there are few published series of malignant vascular tumors in patients age < or = 21 years. METHODS: The authors retrospectively documented the clinical presentation, pathology, treatment, and outcome of patients age < or = 21 years with malignant vascular tumors treated between 1970-1995 at Memorial Sloan-Kettering Cancer Center. The histologic sections were rereviewed to confirm the diagnosis. RESULTS: Four patients were identified with angiosarcoma and two with malignant hemangioendothelioma. Five patients were female and one was male; the median age at diagnosis was 11.8 years (range, 8 months-21 years). The tumor involved the skin in one patient, soft tissue in one patient, bone in two patients, and internal organs in two patients. One patient had associated diffuse angiomatosis and another had the Klippel-Trenaunay-Weber syndrome. This patient received prior radiation therapy to the primary site with the subsequent development of a vascular sarcoma. None of the patients had distant metastases at diagnosis. Resection was attempted in five patients and completed in four. Chemotherapy alone was given to three patients whereas radiation therapy alone and radiation plus chemotherapy were administered to one patient each. The median follow-up was 4.9 years (range, 1 month-12 years). There were three deaths from progressive disease and two deaths from locoregional recurrences. Reexcision and radiotherapy controlled one local recurrence. Another patient developed recurrence to regional lymph nodes and further dissemination. The primary tumor in all three survivors was excised completely whereas two of the three patients who died of progressive disease underwent an incomplete excision or biopsy alone. CONCLUSIONS: Malignant vascular tumors are rare in the first two decades of life and when they do occur are very aggressive. Complete resection is curative for patients with localized lesions.

Adolescent↗
PubMed1998

In vivo transfer of barley stripe mosaic hordeivirus ribonucleotides to the 5' terminus of maize stripe tenuivirus RNAs.

The Tenuivirus maize stripe virus (MStV) shares many properties with viruses in the genus Phlebovirus of the family Bunyaviridae. Besides genome organization and gene expression strategies, one property shared by these plant- and vertebrate-infecting viruses is that transcription gives rise to virus-specific mRNAs containing nonviral 5'-terminal nucleotide sequences. The 5'-terminal nucleotides are believed to be derived from host mRNA sequences as a result of "cap-snatching." We investigated whether specific nucleotide sequences could serve as primer donors for cap-snatching in vivo. Barley (Hordeum vulgare) plants were singly and doubly infected with MStV and the Hordeivirus barley stripe mosaic virus (BSMV). A reverse transcription-PCR assay was used to identify chimeric BSMV/MStV RNAs. Specific reverse transcription-PCR products were detected from doubly infected plants by using one PCR primer corresponding to the 5' termini of the BSMV RNAs (alpha, beta, and gamma) and a second primer complementary to MStV RNA 4. The resulting cDNAs were cloned, and nucleotide sequence analysis showed them to be chimeric, containing BSMV 5'-terminal sequences as well as MStV RNA 4 sequences. All clones contained the BSMV RNA 5' primer nucleotide sequence, but they also showed characteristics common to Tenuivirus mRNAs. More than 80% of the clones contained BSMV RNA nucleotides not present on the PCR primer. Several lacked the exact 5' terminus of MStV RNA 4, a feature also seen for viruses in the Bunyaviridae. These data show that heterologous virus RNAs (BSMV) can serve as primer donors for MStV mRNA capped RNA-primed transcription in doubly infected plants.

DNA Primers↗
PubMed1998

Masoprocol (nordihydroguaiaretic acid): a new antihyperglycemic agent isolated from the creosote bush (Larrea tridentata).

An ethnomedically-driven approach was used to evaluate the ability of a pure compound isolated from the creosote bush (Larrea tridentata) to lower plasma glucose concentration in two mouse models of type 2 diabetes. The results indicated that plasma glucose concentration fell approximately 8 mmol/l in male C57BL/ks-db/db or C57BL/6J-ob/ob mice following the oral administration of masoprocol (nordihydroguaiaretic acid), a well known lipoxygenase inhibitor. The decline in plasma glucose concentration following masoprocol treatment in the mice was achieved without any change in plasma insulin concentration. In addition, oral glucose tolerance improved and the ability of insulin to lower plasma glucose concentrations was accentuated in masoprocol-treated db/db mice. These data raise the possibility that masoprocol, or other lipoxygenase inhibitors, represents a new approach to the pharmacological treatment of Type 2 diabetes.

Animals↗