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Biomedical subjects

Y C Chang

Publications and source records attributed to Y C Chang.

At least 163 records · Page 9Linked to original sources

Effects of gamma knife radiosurgery for brain tumors: clinical evaluation.

BACKGROUND: Gamma knife radiosurgery is a safe and effective alternative to microsurgery in the management of selected intracranial lesions. In our initial three-year experience with gamma knife radiosurgery, 431 patients were treated using this method. This report presents the treatment results for three different types of brain tumors: benign meningiomas, malignant metastases and gliomas. METHODS: A retrospective study was performed to analyze a consecutive series of 71 meningiomas, 31 metastatic tumors and 21 gliomas treated by gamma knife radiosurgery between March 1993 and May 1996. The treatment results were investigated using regular magnetic resonance examinations and tumor volume measurement at six-month intervals to observe sequential changes of the tumors. Patients with meningiomas were further divided into three groups according to the peripheral radiation doses: high-dose (20-17 Gy, n = 18), medium-dose (16-15 Gy, n = 33) and low-dose (14-12 Gy, n = 20). The Generalized Estimation Equation was applied to compare treatment results in these three groups with different doses and tumor volumes. RESULTS: Volume measurements of the 71 meningiomas showed that 76% decreased in size, 16% stabilized and 8% increased in size. The volumes increased most frequently in the early stage (6-12 months) after treatment and subsequently regressed after the twelfth month. The tumor control rate for meningiomas in our three-year follow-up was over 90%. For meningiomas, the statistical analysis showed that both the radiation dose and tumor volume were significantly related to the development of adverse radiation effects (p < 0.05). In metastatic tumors, rapid tumor regression after radiosurgery was found in 87% of the patients. In gliomas, radiosurgery effectively inhibited tumor growth in selected patients with small, circumscribed, less infiltrative tumors. Ependymomas and low-grade astrocytomas had more favorable outcomes than other gliomas. CONCLUSIONS: Gamma knife radiosurgery is effective for controlling tumor growth in benign meningiomas for up to three years after surgery. In selected cases of malignant metastasis and gliomas, most patients appeared to benefit from the treatment with symptomatic improvement and prolonged survival. Treatment strategy and dose selection in radiosurgery should be adjusted to optimize tumor control and avoid adverse radiation effects.

Brain Neoplasms↗

Technetium-99m-HMPAO brain SPECT in neonates with hypoglycemic encephalopathy.

Regional brain injury in three neonates with hypoglycemic encephalopathy are presented using serial 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT and, for comparison, MRI. During the acute stage, both 99mTc-HMPAO SPECT and MRI reveal abnormalities in the posterior cerebrum. Technetium-99m-HMPAO SPECT reveals further areas of insult, for example the frontal lobes. The degree of hypoperfusion correlates with the clinical severity of hypoglycemia during the neonatal period and subsequent neurological sequelae. Follow-up with HMPAO SPECT several months after insult demonstrates persistent hypoperfusion in some areas, mainly in the occipital and posterior parietal regions. MRI can depict morphological changes with superior resolution. Because morphological change generally follows slowly after functional change, MRI is less sensitive than HMPAO SPECT in detecting and predicting the extent of hypoglycemic cerebral injury during the acute phase. HMPAO SPECT during the acute stage is a valuable tool for evaluating the extent and severity of brain injury in neonates with hypoglycemic encephalopathy.

Brain↗

Cryptococcus neoformans: virulence and host defences.

Cryptococcus neoformans represents a model organism for the study of virulence and the host response. In this discussion, there is a focus on the genetic, molecular, and biochemical aspects of C. neoformans as it interacts with the host. Investigations into direct and indirect virulence phenotypes are now possible. The molecular aspects of two major virulence factors, capsule and melanin, are characterized. Yeast polyol metabolism through mannitol is examined as a potential biochemical pathway for virulence. The concept of C. neoformans differentially expressed genes within the host or in response to certain environmental cues can be used indirectly to identify potential virulence genes. However, despite significant progress in molecular pathogenesis with C. neoformans, the future of research in this area will require a certain critical mass of investigators to help share in the developmental costs which continue to occur.

Cryptococcosis↗

Dose-dependent reduced haloperidol/haloperidol ratios: influence of patient-related variables.

Plasma reduced haloperidol (RH) concentrations or RH to haloperidol (HL) ratios have been suggested to be important in determining the clinical efficacy and extrapyramidal side effects of HL. In this study, we measured the steady-state plasma HL and RH levels by high performance liquid chromatography and analyzed the effects of various variables (dose, gender, age, and body weight) on RH/HL ratios in four dose groups of Chinese schizophrenic inpatients: 10 mg/day (n = 84), 20 (n = 111), 30 (n = 29), and 60 (n = 55). In addition, the polymorphic distribution of RH/HL ratios, suggested by previous investigators, was further tested in each dosage group (for controlling the potential dosage effect on RH/HL ratios). As a result, both age and body weight could influence RH/HL ratios. Each year increase in age (after adjusting the effects of gender, body weight, and dosage) would elevate the RH/HL ratio by 0.0067 (P < 0.0001). On the other hand, after adjusting gender, age, and dosage effects, each kg increment in body weight would decrease the RH/HL ratio by 0.0044 (P < 0.01). Gender did not influence the ratio. Furthermore, the high dosage groups had higher RH/HL ratios (even with other variables being controlled). In comparison with the 10 mg group, the 60 mg group exhibited a higher mean RH/HL ratio by 0.84 (P < 0.0001) and the 30 mg group did by 0.31 (P < 0.0001). The 20 mg group was almost equal to the 10 mg group in RH/HL ratios. Besides, at each dosage group, the frequency distribution of RH/HL ratios seemed to be predominantly unimodal with a small proportion of extreme outliers. The results of this study clearly indicate that aging or a high dose (> or = 30 mg/day) of HL could raise the plasma RH/HL ratio, while an increasing body weight would reduce that. In contrast, gender does not affect the ratios.

Adult↗

Transcriptional squelching by ectopic expression of E2F-1 and p53 is alleviated by proteasome inhibitors MG-132 and lactacystin.

The transcription factors p53 and E2F-1 play important roles in the control of cell cycle progression. In transient transfection experiments, expression of E2F-1, other E2F family members, or p53 squelched transcription from cotransfected plasmids in a dose-dependent manner. Although the proteasome inhibitors MG-132 and lactacystin markedly increased the level of expression of E2F-1 and p53, these inhibitors completely alleviated squelching by both proteins. Several observations indicate MG-132 alleviates squelching by influencing the conformation of newly synthesized p53 and E2F-1:MG-132 increased the fraction of wild type p53 bound by a monoclonal antibody which preferentially recognizes mutant conformers of p53, increased binding of hsp70 to p53 and inhibited nuclear accumulation of both p53 and E2F-1, but not the pocket protein p107. The protease inhibitors ALLN and ALLM did not influence expression of E2F-1 or p53, nor did they alleviate squelching by either transcription factor. Because MG-132 and lactacycstin are highly specific inhibitors of the proteasome protease, our results suggest that the proteasome influences post-translational processes involved in proper folding and cytoplasmic clearing of E2F-1 and p53.

Acetylcysteine↗

Measurements of serum müllerian inhibiting substance in the evaluation of children with nonpalpable gonads.

BACKGROUND: Müllerian inhibiting substance, produced constitutively by the prepubertal testes, promotes involution of the müllerian ducts during normal male sexual differentiation. In children with virilization and nonpalpable gonads, only those with testicular tissue should have detectable serum concentrations of müllerian inhibiting substance. METHODS: We measured serum mullerian inhibiting substance in 65 children with virilization at birth and nonpalpable gonads (age at diagnosis, 2 days to 11 years) and serum testosterone in 54 of them either after the administration of human chorionic gonadotropin or during the physiologic rise in testosterone that occurs in normal infants. RESULTS: The mean (+/-SD) serum mullerian inhibiting substance concentration in the 17 children with no testicular tissue was 0.7+/-0.5 ng per milliliter, as compared with 37.5+/-39.6 ng per milliliter in the 48 children with testes (P<0.001). In the latter group, the mean values in the 14 children with abnormal testes and the 34 with normal testes were 11.5+/-11.8 and 48.2+/-42.1 ng per milliliter, respectively (P< 0.001). The sensitivity and specificity of the serum müllerian inhibiting substance assay for detecting the absence of testicular tissue were 92 percent and 98 percent, respectively, as compared with 69 percent and 83 percent for the measurement of serum testosterone. Furthermore, measurement of serum mullerian inhibiting substance was more sensitive than serum testosterone measurement for the identification of children with abnormal testes (67 percent vs. 25 percent), whereas the specificity of the two tests was similar. CONCLUSIONS: Measurements of serum mullerian inhibiting substance can be used to determine testicular status in prepubertal children with nonpalpable gonads, thus differentiating anorchia from undescended testes in boys with bilateral cryptorchidism and serving as a measure of testicular integrity in children with intersexual anomalies.

Anti-Mullerian Hormone↗

A novel NMDA receptor antagonist protects against N-methyl-D-aspartate- and glutamate-induced neurotoxicity in the goldfish retina.

4(R)-(3-Phenylpropyl)-2(S)-glutamic acid, C(3), is a synthetic analogue of L-glutamate. This analogue reversibly inhibits the membrane depolarization of neurons in the CA1 region of rat hippocampal slices evoked by N-methyl-D-aspartate (NMDA), with an EC50 value of 3.6 microM, whereas the depolarization of these neurons evoked by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid is not inhibited by C(3). Analyses of the inhibitory effect of C(3) on NMDA-evoked currents of dissociated rat hippocampal neurons further revealed that C(3) acts as a competitive antagonist of NMDA receptors and that the inhibitory action of C(3) is not use-dependent. Using goldfish retina as a model, we found that the neuronal damage produced by glutamate or by NMDA was effectively prevented by C(3). Incubation of retinas with high concentrations of C(3), up to 1 mM, did not induce pathomorphological changes in retinal neurons. These results suggest that C(3) is a useful neuroprotectant against excitotoxic damage of neurons.

Animals↗

Level of transforming growth factor beta 1 is elevated in cerebrospinal fluid of children with acute bacterial meningitis.

We investigated the levels of transforming growth factor beta 1 (TGF-beta 1) in cerebrospinal fluid (CSF) in children with meningitis, with a view to prognostic relevance. CSF TGF-beta 1 levels on admission were measured by a sandwich enzyme immunoassay in children with bacterial meningitis (n = 16), aseptic meningitis (n = 12), and control subjects without evidence of central nervous system (CNS) infection (n = 16). Patients were followed up for a mean duration of 13 months, and neurodevelopmental sequelae was determined for those with bacterial meningitis. On admission, CSF TGF-beta 1 levels were significantly higher in children with bacterial meningitis (mean, standard error, 32.92, 2.36 pg/ml) as opposed to those with aseptic meningitis (25.26, 1.72 pg/ml) (P = 0.0155), or control subjects (20.53, 1.05 pg/ml) (P < 0.0001). The CSF TGF-beta 1 levels in children with aseptic meningitis were higher than those in the control group, but without significance (P = 0.02). No apparent correlation existed between CSF TGF-beta 1 levels and CSF protein or cell counts in patients with bacterial meningitis. No significant difference in CSF TGF-beta 1 levels was found between patients with or without major sequelae following bacterial meningitis.

Acute Disease↗

Risk factor of complications requiring neurosurgical intervention in infants with bacterial meningitis.

Among 50 consecutive cases of bacterial meningitis in infants aged 6 months or less, 9 (Group I) were confirmed to have complications requiring neurosurgery during the first 2 weeks of antibiotic treatment. Neurosurgery was performed in 40, 33, and 30% of cases caused by Streptococcus pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, respectively. There were 5 cases of subdural empyema, 1 case of brain abscess, 1 case of subdural empyema and brain abscess, and 2 cases of ventriculitis with severe hydrocephalus. All complications requiring neurosurgery were initially detected by cranial ultrasonography. The other 41 patients who did not undergo neurosurgery were classified as Group II. Comparison of clinical presentations and laboratory findings between the two groups showed that Group 1 contained more patients with a history of inadequate treatment, and longer duration of illness before diagnosis. Except for prolonged disturbance of consciousness, there was no difference between the two groups in clinical and laboratory data on admission or in clinical course during therapy. Due to the high incidence of complications requiring neurosurgical treatment, cost-effective cranial ultrasound is recommended for screening every young infant with bacterial meningitis, especially in cases caused by S. pneumoniae.

Anti-Bacterial Agents↗

Aspergillus fumigatus arp1 modulates conidial pigmentation and complement deposition.

Aspergillus fumigatus is an important pathogen causing invasive pulmonary aspergillosis in immunocompromised patients. The fungus propagates by conidia, which are the infectious structures inhaled by the human host. Opsonophagocytosis is thought to contribute to clearance of the inhaled conidia, a process that is facilitated by complement deposition on conidial surfaces. We now show that conidial colour mutants exhibit significant increases in C3 binding capacity compared with wild type. A reddish-pink mutation that led to enhanced C3 binding was complemented by a cosmid clone. A 3.3 kb DNA fragment from the subsequently rescued cosmid was sufficient to restore the bluish-green conidial pigment. The bluish-green transformant exhibited a level of C3 binding similar to that of the parental strain. A gene, designated arp1, was responsible for the complementation. Comparison of the genomic and cDNA sequences of arp1 revealed that it has two introns and encodes a putative protein of 168 amino acids. Arp1 is very similar to scytalone dehydratase, an enzyme involved in 1,8-dihydroxynaphthalene-melanin synthesis in Colletotrichum lagenarium and Magnaporthe grisea. Northern hybridization analysis revealed that arp1 is developmentally regulated, being expressed during conidiation. Disruption of arp1 resulted in reddish-pink conidia and increased C3 binding. Our studies suggest that arp1 modulates the bluish-green pigmentation of conidia as well as complement deposition.

Amino Acid Sequence↗

Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats.

These studies were undertaken to assess the estrogenic and antiestrogenic effects of dietary genistein. To determine estrogenic effects, genistein was mixed into a modified AIN-76 or AIN-93G semipurified diet at 0 (negative control), 150, 375 or 750 microg/g and 17, beta-estradiol at 1.0 microg/g and fed to ovariectomized 70-d-old Sprague-Dawley rats. Estrogenic potency was determined by analyzing uterine weight, mammary gland development, plasma prolactin and expression of uterine c-fos. Dietary genistein (375 and 750 microg/g) increased uterine wet and dry weights (P < 0.05). Mammary gland regression following ovariectomy was significantly inhibited by dietary genistein at 750 microg/g (P < 0.05). Plasma prolactin was significantly greater in ovariectomized rats fed genistein (750 microg/g) compared with comparable rats not receiving genistein. The relative binding affinity of genistein to the estrogen receptor (ER) was 0.01 that of estradiol. Genistein (750 microg/g) induced the uterine expression of c-fos. To evaluate potential antiestrogenic effects, genistein and estradiol were mixed into the modified AIN diets at the doses noted above and fed to ovariectomized rats. Dietary genistein (375 or 750 microg/g) did not inhibit the effects of estradiol on uterine weight, mammary gland development or plasma prolactin. Serum concentration of total genistein (conjugated plus free) in rats fed 750 microg/g was 2.2 micromol/L and free genistein was 0.4 micromol/L. Administration of dietary genistein at 750 microg/g can exert estrogenic effects in the uterus, mammary gland and hypothalamic/pituitary axis. Dietary genistein (750 microg/g) did not antagonize the action of estradiol in estradiol-supplemented ovariectomized rats or in intact rats.

Administration, Oral↗

Evaluation of swallowing safety with fiberoptic endoscope: comparison with videofluoroscopic technique.

Videofluoroscopy has long been viewed as the "gold standard" of swallowing examination for the comprehensive information it provides. However, it is not very efficient and accessible in some practical situations. In this study, we tried to use a modified technique of fiberoptic endoscopic examination of swallowing (FEES) in evaluating dysphagic patients. For each examination, a spoonful of pudding and dyed water were fed in sequence three times. The pharyngeal swallowing events were observed with fiberscope panoramically and videotaped. Twenty-eight chronic dysphagic patients underwent both videofluoroscopy and FEES in 2 weeks. Comparison of the results revealed that disagreements in premature oral leakage to the pharynx, pharyngeal stasis, laryngeal penetration, aspiration, effective cough reflex, and velopharyngeal incompetence were 39.3%, 10.7%, 14.3%, 14.3%, 39.3%, and 32.1%, respectively. FEES was found to be more sensitive in detecting these risky features of swallowing, except with respect to premature leakage. Possible causes of the discrepant results are discussed, and the limitation of videofluoroscopy in practical usage is discussed. FEES is conclusively a safer, more efficient, and sensitive method than videofluoroscopy in evaluating swallowing safety.

Adult↗

A gene homologous to Saccharomyces cerevisiae SNF1 appears to be essential for the viability of Candida albicans.

The SNF1 gene of Saccharomyces cerevisiae (ScSNF1) is essential for the derepression of catabolic repression. We report here the isolation and characterization of an SNF1 homolog from Candida albicans (CaSNF1) which is apparently essential for the viability of this organism. The putative amino acid sequence of CaSNF1 has 68% identity with that of ScSNF1 and can restore the S. cerevisiae snf1 delta mutant's ability to utilize sucrose. Disruption of one of the CaSNF1 alleles resulted in morphological changes and decreased growth rates but did not modify the carbon source utilization pattern. Repetitive unsuccessful attempts to generate a snf1/snf1 homozygote by disruption of the second allele, using various vectors and approaches, suggest the lethal nature of this mutation. Integration into the second allele was possible only when a full-length functional SNF1 sequence was reassembled, further supporting this hypothesis and indicating that the indispensability of Snf1p prevented the isolation of snf1/snf1 mutants. The mutant bearing two disrupted SNF1 alleles and the SNF1 functional sequence maintained its ability to utilize sucrose and produced stellate colonies with extensive hyphal growth on agar media. It was demonstrated that in a mouse model, the virulences of this mutant and the wild-type strain are similar, suggesting that hyphal growth in vitro is not an indicator for higher virulence.

Amino Acid Sequence↗