Biomedical subjects

T J Chen

Publications and source records attributed to T J Chen.

At least 37 records · Page 2Linked to original sources

PubMed2000

High-resolution finite element models with tissue strength asymmetry accurately predict failure of trabecular bone.

The ability to predict trabecular failure using microstructure-based computational models would greatly facilitate study of trabecular structure-function relations, multiaxial strength, and tissue remodeling. We hypothesized that high-resolution finite element models of trabecular bone that include cortical-like strength asymmetry at the tissue level, could predict apparent level failure of trabecular bone for multiple loading modes. A bilinear constitutive model with asymmetric tissue yield strains in tension and compression was applied to simulate failure in high-resolution finite element models of seven bovine tibial specimens. Tissue modulus was reduced by 95% when tissue principal strains exceeded the tissue yield strains. Linear models were first calibrated for effective tissue modulus against specimen-specific experimental measures of apparent modulus, producing effective tissue moduli of (mean+/-S.D.) 18.7+/-3.4GPa. Next, a parameter study was performed on a single specimen to estimate the tissue level tensile and compressive yield strains. These values, 0.60% strain in tension and 1.01% strain in compression, were then used in non-linear analyses of all seven specimens to predict failure for apparent tensile, compressive, and shear loading. When compared to apparent yield properties previously measured for the same type of bone, the model predictions of both the stresses and strains at failure were not statistically different for any loading case (p>0.15). Use of symmetric tissue strengths could not match the experimental data. These findings establish that, once effective tissue modulus is calibrated and uniform but asymmetric tissue failure strains are used, the resulting models can capture the apparent strength behavior to an outstanding level of accuracy. As such, these computational models have reached a level of fidelity that qualifies them as surrogates for destructive mechanical testing of real specimens.

Animals↗

PubMed2000

Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors.

The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms. The net effect of neurotransmitter interaction at the mesolimbic brain region induces "reward" when dopamine (DA) is released from the neuron at the nucleus accumbens and interacts with a dopamine D2 receptor. "The reward cascade" involves the release of serotonin, which in turn at the hypothalmus stimulates enkephalin, which in turn inhibits GABA at the substania nigra, which in turn fine tunes the amount of DA released at the nucleus accumbens or "reward site." It is well known that under normal conditions in the reward site DA works to maintain our normal drives. In fact, DA has become to be known as the "pleasure molecule" and/or the "antistress molecule." When DA is released into the synapse, it stimulates a number a DA receptors (D1-D5) which results in increased feelings of well-being and stress reduction. A consensus of the literature suggests that when there is a dysfunction in the brain reward cascade, which could be caused by certain genetic variants (polygenic), especially in the DA system causing a hypodopaminergic trait, the brain of that person requires a DA fix to feel good. This trait leads to multiple drug-seeking behavior. This is so because alcohol, cocaine, heroin, marijuana, nicotine, and glucose all cause activation and neuronal release of brain DA, which could heal the abnormal cravings. Certainly after ten years of study we could say with confidence that carriers of the DAD2 receptor A1 allele have compromised D2 receptors. Therefore lack of D2 receptors causes individuals to have a high risk for multiple addictive, impulsive and compulsive behavioral propensities, such as severe alcoholism, cocaine, heroin, marijuana and nicotine use, glucose bingeing, pathological gambling, sex addiction, ADHD, Tourette's Syndrome, autism, chronic violence, posttraumatic stress disorder, schizoid/avoidant cluster, conduct disorder and antisocial behavior. In order to explain the breakdown of the reward cascade due to both multiple genes and environmental stimuli (pleiotropism) and resultant aberrant behaviors, Blum united this hypodopaminergic trait under the rubric of a reward deficiency syndrome.

Behavior, Addictive↗

PubMed1999

Kinetics of germanium dioxide in rats.

The kinetics of germanium dioxide (GeO2) in single dose and repeated exposures were investigated in male Wistar rats. In the single dose GeO2 (100 mg/kg BW, p.o.) exposure study, values of several kinetic parameters were shown as follows, a maximum concentration in serum of 15.5+/-0.7 microg/ml (mean +/- S.E.M.), an absorption half-life of 0.7+/-0.1 h (mean +/- S.E.M.), an elimination half-life of 2.3+/-0.5 h (mean +/- S.E.M.), a distribution of the central compartment Vp (3.1+/-0.3 1, mean +/- S.E.M.), and the apparent volume of distribution of the tissue compartment Vt (8.5+/-2.9 1, mean +/- S.E.M.). In the repeated exposure study, 730+/-92 mg GeO2 in 1 1 double-distilled H2O ( = 100 mg/kg/day) was given daily to rats for 4 weeks (p.o.). After sacrificing the rats, the analysis of tissue distribution showed that GeO2 was accumulated in some important organs or tissues in the body, especially the peripheral nerves and kidney. These results indicate that GeO2 could be absorbed rapidly but had a longer elimination half-life in rats. In addition, GeO2 was accumulated especially in the nerves and kidney following long-term exposure.

Animals↗

PubMed1999

Effects of food restriction on mechanical properties of arterial system in adult and middle-aged rats.

The effects of food restriction on the mechanical properties of the vasculature were determined in Long-Evans male rats with different ages. Rats that began food restriction at the ages of 6 months and 12 months were fed on alternate days for 6 months. Rats at the ages of 12 and 18 months were referred to as adult and middle-aged rats and were anesthetized and thoracotomized. The exponentially tapered T-tube model was employed to relate pulsatile pressure and flow signals measured in the ascending aorta. In each age group, food restriction elicited a decrease in body weight as well as basal heart rate but showed no significant change in cardiac output. Arterial blood pressure, total peripheral resistance, and aortic characteristic impedance were not affected by food restriction in middle-aged rats. However, adult food-restricted rats exhibited lower mean arterial blood pressure (99.1 +/- 3.1 mmHg) than did adult ad libitum-fed rats (110.7 +/- 3.0 mmHg). Total peripheral resistance was reduced from 0.645 +/- 0.045 mmHg-min-kg/ml in adult ad libitum-fed rats to 0.492 +/- 0.030 mmHg-min-kg/ml in adult food-restricted rats. Moreover, aortic characteristic impedance of adult food-restricted rats (0.014 +/- 0.001 mmHg-min-kg/ml) was lower than that of adult ad libitum-fed rats (0.024 +/- 0.002 mmHg-min-kg/ml). Neither age nor diet exerted effects on wave transit time and produced no changes in aortic distensibility. In conclusion, food restriction may elicit significant changes in the mechanical properties of both Windkessel vessels and resistance arterioles in adult rats, but not in middle-aged rats.

Aging↗

PubMed1999

Detection of mitochondrial DNA mutations by temporal temperature gradient gel electrophoresis.

BACKGROUND: A unique requirement for the molecular diagnosis of mitochondrial DNA (mtDNA) disorders is the ability to detect heteroplasmic mtDNA mutations and to distinguish them from homoplasmic sequence variations before further testing (e.g., sequencing) is performed. We evaluated the potential utility of temporal temperature gradient gel electrophoresis (TTGE) for these purposes in patients with suspected mtDNA mutations. METHODS: DNA samples were selected from patients with known mtDNA mutations and patients suspected of mtDNA disorders without detectable mutations by routine analysis. Six regions of mtDNA were PCR amplified and analyzed by TTGE. Electrophoresis was carried out at 145 V with a constant temperature increment of 1.2 degrees C/h. Mutations were identified by direct sequencing of the PCR products and confirmed by PCR/allele-specific oligonucleotide or PCR/restriction fragment length polymorphism analysis. RESULTS: In the experiments using patient samples containing various amounts of mutant mtDNA, TTGE detected as little as 4% mutant heteroplasmy and identified heteroplasmy in the presence of a homoplasmic polymorphism. In 109 specimens with 15 different known mutations, TTGE detected the presence of all mutations and distinguished heteroplasmic mutations from homoplasmic polymorphisms. When 11% of the mtDNA genome was analyzed by TTGE in 104 patients with clinically suspected mitochondrial disorders, 7 cases of heteroplasmy ( approximately 7%) were detected. CONCLUSIONS: TTGE distinguishes heteroplasmic mutation from homoplasmic polymorphisms and appears to be a sensitive tool for detection of sequence variations and heteroplasmy in patients suspected of having mtDNA disorders.

Alleles↗

PubMed1999

Atypical central neurocytoma: report of a case.

Central neurocytomas are rare, relatively benign intraventricular neoplasms composed of uniform round cells with neuronal differentiation. The majority of previously reported central neurocytomas did not recurr after tumor removal and the patients had favorable postoperative outcomes. Only a few cases with malignant histopathology or malignant behavior have been noted. Atypical central neurocytoma is a new entity that was first described in the literature in 1997. The tumors have been noted to exhibit a Ki-67 labeling index of 2% or more, or vascular proliferation, mitoses, and necrosis, or both. Atypical histologic findings are usually associated with a somewhat less favorable clinical course and requires postoperative radiotherapy. We report a unique case of a 33-year-old man with a large intraventricular central neurocytoma. The characteristic histopathologic picture, the immunoreactivity for both synaptophysin and neuron-specific enolase, and the ultrastructural features of neuronal differentiation distinguished it from ependymoma and oligodendroglioma. The mitotic activity (up to 3 mitoses/10 high power field) and the high percentage of Ki-67-staining tumor cells (labeling index, 5.0%) in our case were consistent with the atypical variant of central neurocytoma. The patient underwent craniotomy and partial resection of the tumor. Unfortunately, he died of hydrocephalus and brain edema, the next day.

Adult↗

PubMed1998

Variations of prostaglandin E2 receptors in hamster's ovary and endometrium during estrous cycle.

The purpose of this study was to determine concurrent ovarian and endometrial prostaglandin E2 (PGE2) receptor concentrations throughout the hamster estrous cycle. The effect of progesterone (P4) on PGE2 receptor in these two tissues was also investigated during in vitro culture. Estrous cycles of mature female hamsters were monitored according to the appearance of the vaginal discharge on cycle day 1 (D1). Ovaries and uteri were removed from cyclic hamsters at 10:00 a.m. on each day of the cycle and at 6:00 p.m. on D4 (proestrus). Ovarian and endometrial cell membranes were collected and assayed for the specific PGE2 binding by Scatchard plot analysis, using seven different concentrations of 3H-PGE2 (0.72-9.1 nM) with or without the presence of unlabelled PGE2 (9.1 microM). Ovarian and endometrial tissues of the cyclic hamsters were shown to contain a saturable, specific binding site with KD=4.69+/-0.55, and 5.7+/-0.4 nM for ovary and endometrium, respectively. Relative binding activity of PGE1 for the PGE2 binding site was about 28%. PGF2alpha and PGA1 did not compete for the PGE2 binding site. In ovaries, the PGE2 receptor levels started to increase sharply in the evening of D4 and reached maximum in the morning of D1. A precipitous drop of PGE2 receptor was observed on D2 followed by gradual decreases on D3 and D4. The PGE2 receptor concentrations in endometrium were the lowest in the morning of D4, and increased thereafter until a maximal level was reached on D2. Progesterone (10 nM) augmented PGE2 receptors in ovarian but not in endometrial tissue during 24-h in vitro incubation.

Animals↗

PubMed1998

Effect of olivocochlear bundle lesion on locomotor activity in rats.

This study was conducted to investigate the effect of olivocochlear bundle (OCB) lesion on spontaneous locomotor activity in Wistar rats. The OCB is an auditory efferent pathway which originates from the superior olivary complex in the brainstem and terminates within the cochlea. It has an inhibitory effect on the auditory end organs. In the present study, the OCB was damaged at the floor of the fourth ventricle using radiofrequency current. The rats' locomotor activities were then monitored weekly for 2 months using an automated Digiscan activity monitor system. Six behavioral variables were collected and analyzed: horizontal activity (HA), total distance (TD), movement time (MT), vertical activity (VA), stereotypy count (SC), and margin time (MGT). Significant time-dependent increases were noted for HA, TD, VA, and SC following OCB lesion. These results of increasing exploratory and stereotyped behaviors may be caused by the rat experiencing more auditory stimulation than before due to OCB dysfunction and may cause the rat to become more curious to explore its surroundings.

Animals↗

PubMed1998

Development of recombinant human prolactin receptor antagonists by molecular mimicry of the phosphorylated hormone.

Previous studies have demonstrated that naturally phosphorylated PRL antagonizes the growth-promoting effects of unmodified PRL in two different PRL-responsive cell lines. In this study our aim was to produce a molecular mimic of phosphorylated PRL by substituting a fairly bulky, negatively charged amino acid (glutamate or aspartate) for the normally phosphorylated serine [serine 179 in human PRL (hPRL)]. In addition, because of the marked effect of phosphorylation on biological activity, we investigated the importance of the unmodified serine in the growth-promoting activity of PRL. hPRL complementary DNA was obtained from the American Type Culture Collection and subcloned into pT7-SCII after site-directed mutagenesis using the deoxyuridine approach. Proteins were expressed in Escherichia coli BL21 (DE3) and were primarily found in inclusion bodies. Agonist and antagonist activities of each serine 179 mutant were assessed using the Nb2 bioassay. Compared with standard hPRL, the recombinant wild-type was more active in the Nb2 assay, attesting to both the absence, or low level, of endotoxin contamination in preparations from these cells and the appropriate folding of the molecule. The aspartate and glutamate mutants had no intrinsic agonist activity, but both antagonized the growth-promoting activity of wild-type PRL, with the aspartate mutant proving to be a very effective antagonist. Two hundred picograms per ml of the aspartate mutant negated 75% of the growth response to 400 pg/ml wild-type PRL. When serine 179 was mutated to alanine or valine, mutant PRLs with 0% and 14% of the biological activity of wild-type PRL, respectively, were produced. These results demonstrate 1) that molecular mimicry of the phosphorylated hormone does produce a PRL antagonist, and 2) that the serine at position 179 is crucial to the growth-promoting activity of PRL. The aspartate mutant can now be used to study many aspects of the physiology of PRL.

Amino Acid Sequence↗

PubMed1998

Successful resection of sigmoid colon cancer in a patient with factor XI deficiency.

A 42-year-old-women with sigmoid colon adenocarcinoma was found to have isolated prolonged activated partial thromboplastin time (aPTT 102.5 s, normal range 24-36 s) preoperatively. Her medical history included an episode of prolonged postdelivery uterine bleeding 16 years previously. A mixed aPTT test showed immediate correction of the prolonged aPTT, indicating a coagulation factor deficiency in the intrinsic pathway. Factor assays showed factor XI was below 1% of average normal value whereas factor VIII, IX and XII activities were normal. Family screening revealed one sister among the three siblings also had isolated prolonged aPTT. The patient was transfused with four units (5mL/kg) of fresh frozen plasma the day before surgery, then with two units during surgery. The operation was uneventful with no bleeding problems. The patient recovered smoothly and is currently undergoing adjuvant chemotherapy. This is the first formal report of a patient with factor XI deficiency undergoing major surgery in Taiwan. Careful monitoring of aPTT, with fresh frozen plasma transfusion, when needed, may safely overcome bleeding problems during surgery.

Adenocarcinoma↗

PubMed1998

Dimethylformamide-induced occupational liver injury--a case report.

Dimethylformamide(DMF), a widely used industrial solvent, has been reported to induce subtle to clinically overt hepatotoxicity. Liver injury due to occupational exposure through inhalation and skin contact have been sporadically reported. We reported a 42-year-old male Taiwanese who developed progressive, intermittent abdominal pain for 6 months after working in a synthetic leather factory. Acute hepatitis episode occurred after working in an enclosed and poorly-ventilated workplace for one day. Based on occupational history, pathological examination and serial liver function examinations, the case was compatible with DMF-induced acute chemical hepatitis.

Adult↗

PubMed1998

The suppressive effect of the olivocochlear bundle in rats studied by brainstem auditory evoked potentials following brainstem lesion.

The olivocochlear bundle (OCB) stems from the superior olivary complex in the brainstem and projects to the ipsilateral and contralateral cochlea. Several studies have suggested that the OCB has a suppressive effect on the inner ear by inhibiting the responses of the primary afferent fibers. To evaluate the action of OCB by more available measurement, radiofrequency lesion was applied to 30 Wistar rats which were divided into four groups, a sham group and another three groups with different OCB lesion sites. Consequent changes following OCB lesion were evaluated by measuring the brainstem auditory evoked potentials (BAEPs), which are considered to reflect the auditory brainstem afferent conduction. The amplitudes and latencies did not change significantly after sham treatment. However, although the BAEP peak latencies were not significantly altered after damaging the OCB, the amplitudes of the BAEP waves I to III were augmented significantly. These results indicate that increased neural activities were presented in the auditory nerves, cochlear nucleus and the superior olivary complex upon disinhibition of the OCB. Unilateral OCB lesions predominantly augmented BAEP waveform which was recorded ipsilaterally to the lesion side. Upon lesion of the midline OCB, BAEP recordings on either side showed significant increments in the amplitudes of waves I to III. These findings are compatible with those observed in the cat model and other rodents, and thus confirm that (1) OCB lesion leads to increased amplitudes in some BAEP peaks which were evoked by certain hyperactive auditory nuclei and tracts; and (2) BAEP measurment is a convenient and useful tool for assessing the OCB function.

Animals↗

PubMed1997

A study of the referral patterns of obstetric clinics and the performance of receiving neonatal intensive care units in Taiwan.

To study the referral patterns of obstetric clinics, and the performance of receiving intensive care units measured by the survival of transported neonates, transport records were collected prospectively between July, 1991 and June, 1992. Two hundred and fifty-four transported neonates born in 51 obstetric clinics (level I units) in Tainan City and County, in southern Taiwan, were enrolled in this study. Nineteen percent of the transported neonates were very low birthweight infants (< 1500 g). Nearly equal numbers of them were transported to eight district hospitals (level II units) and to a tertiary center (level III unit), but these infants were 1.5 times more likely to die in a level II unit than a level III unit. In addition, equal numbers of infants assisted by mechanical ventilators were transported to level II and III units, but these infants were three times more likely to die in a level II unit than a level III unit (P = 0.006). Seventy-seven percent of the normal birthweight infants (> or = 2500 g) were transported to level II units, and the mortality in this group was 12.3% compared with 0% in those transported to the level III unit. Approximately 56% of these normal birthweight infants in level II units died of severe birth asphyxia. The referral patterns of level 1 units had an unfavorable effect on the survival of neonates requiring mechanical ventilation. Enhancing the skills of the staff in level I units to recognize and stabilize such infants, elevating the capability of level II units in treating some of these cases, and increasing the hospital beds for level III care are necessary to increase their chance of survival.

Health Services Research↗

PubMed1997

Three-dimensional imaging of trabecular bone using the computer numerically controlled milling technique.

Although various techniques exist for high-resolution, three-dimensional imaging of trabecular bone, a common limitation is that resolution depends on specimen size. Most techniques also have limited availability due to their expense and complexity. We therefore developed a simple, accurate technique that has a resolution that is independent of specimen size. Thin layers are serially removed from an embedded bone specimen using a computer numerically controlled (CNC) milling machine, and each exposed cross section is imaged using a low-magnification digital camera. Precise positioning of the specimen under the camera is achieved using the programmable feature of the CNC milling machine. Large specimens are imaged without loss of resolution by moving the specimen under the camera such that an array of field-of-views spans the full cross section. The images from each field-of-view are easily assembled and registered in the postprocessing. High-contrast sections are achieved by staining the bone black with silver nitrate and embedding it in whitened methylmethacrylate. Due to the high contrast nature and high resolution of the images, thresholding at a single value yielded excellent predictions of morphological parameters such as bone volume fraction (mean +/- SD percent error = 0.70 +/- 4.28%). The main limitations of this fully automated "CNC milling technique" are that the specimen is destroyed and the process is relatively slow. However, because of its accuracy, independence of image resolution from specimen size, and ease of implementation, this new technique is an excellent method for ex situ imaging of trabecular architecture, particularly when high resolution is required.

Bone and Bones↗

PubMed1997

Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB).

The dopaminergic system, and in particular the dopamine D2 receptor, has been implicated in reward mechanisms in the brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance-seeking behaviors (ethanol, drugs, tobacco, and food) and other related behaviors (pathological gambling, Tourette's disorder, attention-deficit/hyperactivity disorder). This is the first study supporting a strong association between the dopamine D2 receptor Taq A1 allele with schizoid/avoidant behavior (SAB). Additionally, an albeit weaker association between the 480-bp VNTR 10/10 allele of the dopamine transporter (DAT1) gene with SAB was similarly found.

Adult↗

PubMed1997

Enhancement of attention processing by Kantroll in healthy humans: a pilot study.

This is the first report in humans of the effects of daily ingestion of a specific amino acid mixture, Kantroll, on cognitive event-related potentials (ERPs) associated with performance. Cognitive ERPs were generated by two computerized visual attention tasks, the Spatial Orientation Task (SOT) and Contingent Continuous Performance Task (CCPT), in normal young adult volunteers, where each subject acted as his own control for testing before and after 28-30 days of amino acid ingestion. A statistically significant amplitude enhancement of the P300 component of the ERPs was seen after Kantroll for both tasks, as well as improvement with respect to cognitive processing speeds. The enhancement of neurophysiologic function observed in this study on normal controls is consistent with the facilitation of recovery of individuals with RDS (i.e., substance use disorder, ADHD, carbohydrate bingeing) following the ingestion of the amino acid supplement, Kantroll, and warrants additional placebo-controlled, double-blind, studies to confirm and extend these results.

Adult↗

PubMed1997

Synergestic effects of noise and aminoglycoside antibiotic (gentamicin) on auditory function in the gerbil.

Exposure to excessive noise can cause auditory impairment in people as well as in animals, which can be aggravated by many different ototoxic substances, such as aminoglycosides. In the present study, the gerbil was selected as the experimental animal because the gerbil has low-frequency auditory sensitivity that is similar to human beings. Auditory function in gerbils upon exposure to noise and/or gentamicin was evaluated from non-invasive records of brainstem auditory evoked potentials (BAEPs). Fifty mature male Mongolian gerbils were divided randomly into four groups. The control group was exposed neither to noise nor to gentamicin. The noise group was exposed to 100dBA noise ten hours a day for four weeks. The gentamicin group was treated with one dose of gentamicin, 75 mg/Kg i.m., daily for four weeks. The noise + gentamicin group was exposed concurrently to both noise and gentamicin treatment. BAEPs were recorded from all gerbils 24 hours before any experimental treatment, then every week for eight consecutive weeks. Long-term exposure to noise and/or gentamicin treatment was found to reduce gerbil's body weight. The increase in auditory threshold upon concurrent exposure to both noise and gentamicin treatment (evaluated from BAEPs) exceeded the sum of effects caused by exposure to noise alone and to gentamicin alone. Although differences of peak or interpeak latencies among the four groups were not statistically significant, large standard deviations were noted in the noise+gentamicin group. Thus the apparent threshold shifts in gerbils indicated a major noise and/or gentamicin induced auditory impairment to the cochlea, and the slight latency variations probably suggested a minor injury to the auditory pathways. We emphasize that noise and aminoglycoside antibiotic gentamicin can cause damage to the hearing ability at the frequency range vital to human speech recognition, and their effects are synergetic.

Animals↗

PubMed1997

Afferent loop syndrome complicated by a duodenal phytobezoar after Billroth-II subtotal gastrectomy.

We illustrate a rare late onset (10 yr) complication of gastric surgery with a combination of afferent loop syndrome and a large duodenal bezoar. The patient underwent a subtotal gastrectomy with Billroth II gastrojejunal anastomosis for benign peptic ulcer 10 yr ago. It was not until several days before this presentation that he suffered from epigastralgia and abdominal distension. Leukocytosis and abnormal blood biochemistry were found including amylase, lipase, alkaline phosphatase, total bilirubin, GOT, and GPT in which amylase was markedly elevated to 1188 U/L. Abdominal ultrasound scan and especially CT scan confirmed the diagnosis of a large bezoar in the dilated duodenal afferent loop. To our knowledge, the rare entity in our case is the first reported in the literature.

Abdominal Pain↗