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Biomedical subjects

Y C Chang

Publications and source records attributed to Y C Chang.

At least 145 records · Page 8Linked to original sources

Characterization of granular particles isolated from postsynaptic densities.

We describe here the isolation and biochemical characterization of a population of protein aggregates from the postsynaptic density (PSD) prepared from pig cerebral cortex. The protein constituents of these aggregates are linked together primarily by disulfide bonds. Negative staining electron microscopy revealed that the isolated protein aggregates were granular objects with an average outside diameter of approximately 21 nm and with small protrusions on their surface. The major constituents of the isolated granular aggregates consist of tubulin and an unidentified protein of 70 kDa in size. Small amounts of the alpha subunit of calcium/calmodulin-dependent protein kinase II and subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and NMDA subtypes of glutamate receptors were also detected by immunoblotting. Actin, however, was not found in these granular aggregates. We propose that these granular protein aggregates correspond to the approximately 20-nm-diameter granular particles of the PSD on the basis of their biochemical and morphological characteristics. The spatial arrangement of these granular aggregates relative to other components of the postsynaptic terminal is also postulated here.

Animals↗

Effect of isoflavones genistein and daidzein in the inhibition of lung metastasis in mice induced by B16F-10 melanoma cells.

Two dietary soybean isoflavones, genistein and daidzein, were studied for the inhibition of lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice. The isoflavone genistein at 200 mumol/kg body wt significantly inhibited (53.6%, p < 0.001) lung tumor nodule formation. The lung collagen hydroxyproline content and the serum sialic acid level, a marker of metastasis, were also significantly lower in these animals than in untreated tumor-bearing animals. Genistein treatment also increased the life span of the tumor-bearing animals (47.7%, p < 0.001). The isoflavone daidzein had no significant effect on the reduction of lung metastasis induced by B16F-10 melanoma cells.

Animals↗

Malignancy may adversely influence the quality and behaviour of oocytes.

A case series of eight cycles of in-vitro fertilization (IVF) in five women diagnosed with malignant disorders is presented. These patients chose to defer definitive treatment for a chance for preservation of potential fertility. The response of these patients to ovarian stimulation, and the outcome, was compared with 17 IVF cycles in 12 age-matched patients with isolated tubal infertility. An apparent adverse influence of malignant disease on the quality and behaviour of oocytes was observed. Despite a comparable total number of oocytes per cycle in the two groups, a significantly reduced percentage of mature oocytes was retrieved per cycle from patients with malignant diseases. The oocytes from patients with malignant disorders were of a poorer quality and exhibited a significantly impaired fertilization rate compared to the controls. We propose that neoplastic processes, irrespective of the site or cell of origin, may have a detrimental impact on the biology of oocytes, an effect akin to that seen on spermatozoa in men with certain malignancies.

Adenocarcinoma↗

Aetiologies and prognosis of Chinese patients with deep vein thrombosis of the lower extremities.

Deep vein thrombosis (DVT) of the lower extremities is not frequently encountered in Oriental patients. We investigated its aetiology and prognosis in 143 patients (65 males, 78 females), presenting to the National Taiwan University Hospital over 4.3 years, diagnosed by colour Doppler ultrasonography. Swelling and pain of the lower extremities were the most frequent presenting symptoms. The left femoropopliteal veins were more frequently involved than other parts of the lower extremities. In these patients, malignancy with or without intravenous catheterization was the most frequent cause (39 patients, 27%). Other common aetiologies included coagulopathy (29 patients, 20%), immobilization (24 patients, 17%) and catheter-related (13 patients, 9%). No definite aetiology could be determined in 37 patients (26%). During follow-up, 27 patients (19%) died, mostly with malignancy. Pulmonary embolism was noted in 16 patients and was not significantly directly related to death. Compared to similar studies in Caucasian patients, there were significant differences in the aetiology of DVT, with malignancy and coagulopathy more common in these Chinese patients.

Adolescent↗

Acute symptomatic seizure disorders in young children--a population study in southern Taiwan.

PURPOSE: To determine the incidence, etiology, and prognosis of acute symptomatic seizures in children by age 3 years. METHODS: In a population-based birth cohort study of all 15,209 neonatal survivors born in Tainan City between October 1989 and December 1991, parents or caretakers of 13,493 children aged 3 years were surveyed by telephone regarding any provoked convulsive disorder, particularly acute symptomatic seizure, in the children; medical records were reviewed. RESULTS: Sixty-three children (39 boys, 24 girls) had acute symptomatic seizures (incidence 0.46 in 100). The leading causes of acute symptomatic seizures were acute gastroenteritis, encephalitis/encephalopathy, and bacterial meningitis. Age-specific incidence was highest in the group aged 1-12 months. Intracranial hemorrhage, bacterial meningitis, and metabolic disturbance were the major causes of acute symptomatic seizures in children aged 1-12 months. Acute gastroenteritis, encephalitis/encephalopathy, and bacterial meningitis accounted for 85% of the causes in children aged 13-24 months, and gastroenteritis and encephalitis/encephalopathy were the predominant causes in those aged 25-36 months. By age 5 years, subsequent unprovoked seizures developed in 14% of the survivors of acute symptomatic seizures. CONCLUSIONS: Many acute symptomatic seizures are preventable. The risk of subsequent unprovoked seizures is determined by underlying precipitating factors. Public education regarding the danger of shaken-baby syndrome and excessive water supplement, as well as and nationwide vaccination against bacterial meningitis in young children, is necessary.

Acute Disease↗

Cytotoxic and non-genotoxic effects of arecoline on human buccal fibroblasts in vitro.

Betel quid chewing has been linked to oral submucous fibrosis and oral cancer. Cytotoxicity and genotoxicity assays were used to investigate the pathobiological effects of arecoline on cultured human buccal fibroblasts. Arecoline increased double-stranded polynucleic acid at the concentration of 0.1 to 10 micrograms/ml in a concentration-dependent manner. At a concentration higher than 50 micrograms/ml, arecoline was cytotoxic to cultured fibroblasts and the cytotoxicity was dose-dependent. No genotoxicity for arecoline was found even at a concentration of 400 micrograms/ml. On the other hand, 600 micrograms/ml glutathione (GSH) and 200 micrograms/ml glycyrrhizin could prevent the arecoline-induced cytotoxicity. These results indicate that arecoline is a cytotoxic agent and no genotoxicity was found to human buccal fibroblasts. Furthermore, increasing consumption of GSH- and glycyrrhizin-rich foods may reduce the oral diseases associated with betel quid chewing.

Anti-Inflammatory Agents, Non-Steroidal↗

Isolation of the third capsule-associated gene, CAP60, required for virulence in Cryptococcus neoformans.

A polysaccharide capsule is one of the most important virulence factors for the pathogenic fungus Cryptococcus neoformans. We previously characterized two capsule-associated genes, CAP59 and CAP64. To further dissect the molecular mechanism of capsule synthesis, 16 acapsular mutants induced by 4-nitroquinoline-1-oxide were obtained. The acapsular phenotype of one of these mutants was complemented. The cloned gene was designated CAP60, and deletion of this newly described capsule-associated gene resulted in an acapsular phenotype. The proposed 67-kDa Cap60p contains 592 amino acids and appears to have a putative transmembrane domain close to the N terminus. DNA sequence analysis revealed that CAP60 has similarity to CAP59 at the center portion of its coding regions. Contour-clamped homogeneous electric field blot analysis suggested that these two genes are on the same chromosome. CAP60 and CAP59, however, could not be functionally substituted for each other by direct complementation or by domain swap experiments. In addition, CAP60 is closely linked to a gene which is similar to a cellulose growth-specific gene of Agaricus bisporus, CEL1. Immunogold electron microscopy studies of the epitope-tagged CAP60 gene revealed that Cap60p was primarily localized to the nuclear membrane. Animal model studies indicated that CAP60 is essential for virulence. Thus, CAP60 is required for both capsule formation and virulence.

Amino Acid Sequence↗

The developmentally regulated alb1 gene of Aspergillus fumigatus: its role in modulation of conidial morphology and virulence.

Aspergillus fumigatus, an important opportunistic pathogen which commonly affects neutropenic patients, produces conidia with a bluish-green color. We identified a gene, alb1, which is required for conidial pigmentation. The alb1 gene encodes a putative polyketide synthase, and disruption of alb1 resulted in an albino conidial phenotype. Expression of alb1 is developmentally regulated, and the 7-kb transcript is detected only during the conidiation stage. The alb1 mutation was found to block 1,3,6,8-tetrahydroxynaphthalene production, indicating that alb1 is involved in dihydroxynaphthalene-melanin biosynthesis. Scanning electron microscopy studies showed that the alb1 disruptant exhibited a smooth conidial surface, whereas complementation of the alb1 deletion restored the echinulate wild-type surface. Disruption of alb1 resulted in a significant increase in C3 binding on conidial surfaces, and the conidia of the alb1 disruptant were ingested by human neutrophils at a higher rate than were those of the wild type. The alb1-complemented strain producing bluish-green conidia exhibited inefficient C3 binding and neutrophil-mediated phagocytosis quantitatively similar to those of the wild type. Importantly, the alb1 disruptant had a statistically significant loss of virulence compared to the wild-type and alb1-complemented strains in a murine model. These results suggest that disruption of alb1 causes pleiotropic effects on conidial morphology and fungal virulence.

Amino Acid Sequence↗

Subdural empyema in 10 infants: US characteristics and clinical correlates.

PURPOSE: To investigate the ultrasonographic (US) characteristics of subdural empyema (SDE) and its differentiation from reactive subdural effusion (RSE) in infants with meningitis. MATERIALS AND METHODS: Images in 10 infants with SDE with or without RSE complicating meningitis were retrospectively reviewed and correlated with clinical findings and compared with US and magnetic resonance (MR) images in four infants with meningitis and RSE. RESULTS: At US, 15 of 16 SDEs in the 10 infants were seen as heterogeneous to hyperechoic convexity collections. Hyperechoic strands were seen in 12 SDEs. Other findings included a thick, echogenic inner membrane (n = 9), increased echogenicity of pia-arachnoid and exudates in the subarachnoid space (n = 16), mass effect (n = 16), and loculated extraaxial collections (n = 2). MR imaging findings correlated well with US and surgical results. At computed tomography, SDE was misinterpreted as RSE in one patient, due to the absence of inner membrane contrast material enhancement. Clinical outcome was related to the degree of brain damage consequent to meningitis and the chronicity of SDE. RSEs in seven infants (three with concurrent SDE) were anechoic; an inner membrane was seen in six, and increased pia-arachnoid echogenicity was seen in four. CONCLUSION: SDE has complex US features that are helpful for differentiation from anechoic RSE in infants with meningitis.

Diagnosis, Differential↗

Central nervous system candidiasis in very low-birth-weight premature neonates and infants: US characteristics and histopathologic and MR imaging correlates in five patients.

PURPOSE: To analyze the high-resolution (i.e., 5.0- or 7.5-MHz) ultrasonographic (US) imaging characteristics of central nervous system (CNS) candidiasis and their histopathologic and magnetic resonance (MR) imaging correlates in very low-birth-weight (VLBW) premature neonates and infants with systemic candidiasis. MATERIALS AND METHODS: The US images obtained in one VLBW neonate (age, 24 days; weight, 846 g) and four VLBW infants (age range, 36-161 days; weight range, 800-1, 360 g) with proved CNS candidiasis complicating systemic candidiasis and the clinical (n = 5), histopathologic (n = 3), and MR imaging (n = 2) correlates were retrospectively reviewed. RESULTS: The cranial US findings consisted of parenchymal abnormalities in four and ventricular lesions in three patients. The most common findings were multiple echogenic, rim-like microabscesses (four patients) scattered in the subcortical, periventricular, and basal ganglial areas. Confluent macroabscess formation, seen as echogenic mass-like lesions with hypoechoic centers in the periventricular regions and/or thalami, was noted on the US images obtained in two patients. The ventricles showed dilatation in two, increased ependymal echogenicity in three, the presence of intraventricular echogenic septa in two, and a lumpy choroid plexus or the presence of debris in two patients. US findings correlated well with MR imaging and autopsy findings. The histopathologic changes in the posterior fossa were well demonstrated on MR images but not demonstrated on 5.0- or 7.5-MHz US images. CONCLUSION: CNS candidiasis in VLBW neonates and infants has characteristic US features that may help in the early diagnosis of CNS involvement in systemic candidiasis.

Autopsy↗

The effectiveness and factors related to treatment results of gamma knife radiosurgery for meningiomas.

A retrospective analysis was conducted on 80 patients with intracranial mengiomas treated with Gamma Knife radiosurgery between 1993 and 1996. The purpose was to analyze the efficacy of the treatment and to assess appropriate treatment parameters. The results were assessed by regular MR examinations, and tumor volume was measured at 6-month intervals. Mean follow-up duration was 21 months (range 6-45 months). 63 meningiomas were at the skull base and 17 were distal from the skull base. Tumor volumes <5 ml (n=38), 5-10 ml (n=21), 10-15 ml (n=14), 15-20 ml (n=7). The patients were divided into 3 groups according to the radiation dose. The groups were high-dose (peripheral dose 17-20 Gy, n=19), medium-dose (15-16 Gy, n=33) and low-dose (12-14 Gy, n=28) groups. A statistical method (Generalized Estimation Equation) was applied to compare treatment results in these groups with different doses and tumor volumes. The volume measurement at the latest follow-up showed 74% (59/80) meningiomas decreased in volume, 17% (14/80) had no tumor enlargement and 9% (7/80) had increased in volume. The increased volume was found more frequently in the patients with a short (6-12 months) follow-up period. In this series, the tumors had 32&percnt reduction in average tumor volume at 3 years after radiosurgery. At the range of 12-20 Gy peripheral dose (PD), radiosurgery was effective to reduce tumor volume 0.7% per month (p<0.05). However, higher doses had no significant difference on tumor volume reduction (p>0.05). On the other hand, high-dose (PD>17 Gy) treatment was associated with a higher risk of temporary tumor swelling and the development of adverse radiation effects (AREs). The AREs detected on MR images occurred in (25/80) 31% patients. Only 6/25 AREs were symptomatic and 2 had neurological sequelae. Peripheral doses, tumor volumes and their locations had significant impacts on the ARE (p<0. 05). In conclusion, a peripheral dose of 15-16 Gy may be adequate for meningiomas with small volumes (<5 ml). In larger tumors (>10 ml) a lower PD is preferred (12-14 Gy). To avoid initial tumor swelling and ARE, high-dose irradiation (PD>17 Gy) is not recommended for meningiomas larger than 5 ml.

Adult↗

The relationship between low back discomfort ratings and the NIOSH lifting index.

An epidemiological study was performed to evaluate the relation between low-back discomfort ratings and use of the revised NIOSH lifting guide to assess the risk of manual material handling (MMH) tasks. We surveyed 97 MMH workers on site in 15 factories and designed a questionnaire to systematically collect job-related information. Approximately 90% of the workers had suffered various degrees of lower back discomfort, and 80% had sought medical treatment. The survey showed that 42 of the 97 jobs analyzed had a recommended weight limit of 0, which was attributed to either a horizontal distance or a lifting frequency that exceeded the bounds of the NIOSH lifting index. Apparently, the limits for horizontal distance and maximum allowable frequency are too stringent to accommodate many existing MMH jobs. For the remaining 55 jobs, the significant positive correlation obtained between the lifting index and the severity of low-back discomfort suggests that the lifting index is reliable in assessing the potential risk of low-back injury in MMH. These findings provide useful information on the application of the NIOSH lifting guide to the assessment of low-back pain.

Adolescent↗

Identification of the main generator source of longitudinal muscle contraction in the earthworm ventral nerve cord.

The main generator source of a longitudinal muscle contraction was identified as an M (mechanical-stimulus-sensitive) circuit composed of a presynaptic M-1 neuron and a postsynaptic M-2 neuron in the ventral nerve cord of the earthworm, Amynthas hawayanus, by simultaneous intracellular response recording and Lucifer Yellow-CH injection with two microelectrodes. Five-peaked responses were evoked in both neurons by a mechanical, but not by an electrical, stimulus to the mechanoreceptor in the shaft of a seta at the opposite side of an epidermis-muscle-nerve-cord preparation. This response was correlated to 84% of the amplitude, 73% of the rising rate and 81% of the duration of a longitudinal muscle contraction recorded by a mechanoelectrical transducer after eliminating the other possible generator sources by partitioning the epidermis-muscle piece of this preparation. The pre- and postsynaptic relationship between these two neurons was determined by alternately stimulating and recording with two microelectrodes. Images of the Lucifer Yellow-CH-filled M-1 and M-2 neurons showed that both of them are composed of bundles of longitudinal processes situated on the side of the nerve cord opposite to stimulation. The M-1 neuron has an afferent process (A1) in the first nerve at the stimulated side of this preparation and the M-2 neuron has two efferent processes (E1 and E3) in the first and third nerves at the recording side where their effector muscle cell was identified by a third microelectrode.

Animals↗

Facilitation of the main generator source of earthworm muscle contraction by a peripheral neuron.

A constant facilitation of responses evoked in the earthworm muscle contraction generator neurons by responses evoked in the neurons of its peripheral nervous system was demonstrated. It is based on the proposal that these two responses are bifurcations of an afferent response evoked by the same peripheral mechanical stimulus but converging again on this central neuron. A single-peaked generator response without facilitation was demonstrated by sectioning the afferent route of the peripheral facilitatory modulatory response, or conditioning response (CR). The multipeaked response could be restored by restimulating the sectioned modulatory neuron with an intracellular substitutive conditioning stimulus (SCS). These multipeaked responses were proposed to be the result of reverberating the original single peaked unconditioned response (UR) through a parallel (P) neuronal circuit which receives the facilitation of the peripheral modulatory neuron. This peripheral modulatory neuron was named "Peri-Kästchen" (PK) neuron because it has about 20 peripheral processes distributed on the surface of a Kästchen of longitudinal muscle cells on the body wall of this preparation as revealed by the Lucifer Yellow-CH-filling method.

Animals↗

Persistent attenuation and enhancement of the earthworm main muscle contraction generator response induced by repeated stimulation of a peripheral neuron.

Responses evoked in the earthworm, Amynthas hawayanus, main muscle contraction generator M-2 (postsynaptic mechanical-stimulus-sensitive) neuron by threshold mechanical stimuli in 2-s intertrial intervals (ITI) were used as the control or unconditioned responses (UR). Their attenuation induced by decreasing these intervals in non-associative conditioning and their enhancement induced by associating the unconditioned stimuli (US) to a train of short (0.1 s) hyperpolarizing electrical substitutive conditioning stimuli (SCS) in the Peri-Kästchen (PK) neuron were measured in four parameters, i.e., peak numbers (N) and amplitude (AMP) averaged from 120 responses, sum of these amplitudes (sigma AMP) and the highest peak amplitude (V) over a period of 4 min. Persistent attenuation similar to habituation was induced by decreasing the control ITI to 0.5 s and 2.0 s in non-associative conditioning within less than 4 min. Dishabituation was induced by randomly pairing one of these habituated US to an electrical stimulus in the PK neuron. All four parameters of the UR were enhanced by forward (SCS-US), but not backward (US-SCS), association of the US with 25, 100 and 250-Hz trains of SCS with 40-ms interstimulus intervals (ISI) for 4 min and persisted for another 4 min after turning off the SCS. The enhancement of these parameters was proportional to the SCS frequencies in the train. No UR was evoked by the SCS when the US was turned off after 4 min of classical conditioning.

Animals↗

mdm2 and bax, downstream mediators of the p53 response, are degraded by the ubiquitin-proteasome pathway.

Upon activation in response to cellular stress or DNA damage, the p53 tumor suppressor induces the expression of gene products involved in cell cycle arrest and apoptosis. Using the proteasome-specific inhibitors, MG132 (N-acetyl-L-leucinyl-L-leucinal-L-leucinal) and lactacystin, here we show that the p53-response proteins, bax and mdm2 as well as p21, are degraded by the ubiquitin-proteasome pathway in HeLa cells. MG132 also increased expression of the three proteins in cells that lack p53, showing that stabilization of the p53 response proteins is not due to increased levels of p53 itself. Increases in mdm2 protein levels by MG132 was accompanied by increases in polyubiquitinated forms of the proteins. Our results indicate that ubiquitin-dependent protein degradation influences the turnover of downstream targets of p53, therefore suggesting that the proteasome plays a role in regulating apoptosis and cell cycle arrest in response to p53.

Animals↗

Magnetic resonance angiography in the diagnosis of thoracic venous obstruction.

The aims of this study were to evaluate the diagnostic value of orthogonal magnetic resonance angiography (MRA) and to compare the results of MRA with those of digital subtraction venography (DSV) in thoracic venous diseases. Ten normal volunteers were evaluated using two-dimensional time-of-flight MRA in three orthogonal planes to determine the image quality of each venous segment. Twelve consecutive patients suspected of having thoracic venous disease were studied with both MRA and DSV. In the normal subjects, the plane perpendicular to the target vein provided the most consistent visualization. Using three orthogonal MRA images, a diagnostic-quality image was obtained in 175 (83%) of 210 venous segments in normal volunteers. In patients with thoracic venous obstructive disease, MRA was more effective than DSV in detecting total (84 vs 54), patent (56 vs 36), stenotic (13 vs 10), and obstructive (15 vs 8) venous segments, poststenotic or postobstructive veins (15 vs 10), thrombosis of the internal jugular vein (7 vs 2), intraluminal thrombus (5 vs 3), and azygos veins (12 vs 2). Using venous segments visible on DVS (n = 54) as the standard, the sensitivity and specificity of MRA were 94% and 100%, respectively, in detecting venous patency, and 100% and 98% in detecting complete venous obstruction. In the shoulder region, the sensitivity and specificity of MRA were 93% and 100%, respectively, in detecting venous patency, and 100% and 97% in detecting venous obstruction. We conclude that MRA with three orthogonal planes can provide relatively complete and reliable venous mapping, without the need for contrast medium.

Adult↗

Diagnosis of pulmonary sequestration by magnetic resonance imaging.

Pulmonary sequestration, an uncommon congenital anomaly, is traditionally best diagnosed using arteriography; however, this is invasive and not without risk of morbidity and mortality. We report two patients with pulmonary sequestration diagnosed using magnetic imaging techniques. The first was a 22-year-old woman and the second a 17-year-old boy, both of whom presented with symptoms of cough and exertional dyspnea. Pulmonary sequestration was suspected from their chest radiographs. Magnetic resonance imaging and magnetic resonance angiography clearly demonstrated the aberrant artery arising from the aorta in a single noninvasive examination that did not require the use of contrast medium. We recommend magnetic resonance imaging as a safe, efficient, and noninvasive modality for the diagnosis of pulmonary sequestration.

Adolescent↗