Biomedical subjects

Y C Chang

Publications and source records attributed to Y C Chang.

At least 127 records · Page 7Linked to original sources

PubMed1999

A developmentally regulated gene cluster involved in conidial pigment biosynthesis in Aspergillus fumigatus.

Aspergillus fumigatus, a filamentous fungus producing bluish-green conidia, is an important opportunistic pathogen that primarily affects immunocompromised patients. Conidial pigmentation of A. fumigatus significantly influences its virulence in a murine model. In the present study, six genes, forming a gene cluster spanning 19 kb, were identified as involved in conidial pigment biosynthesis in A. fumigatus. Northern blot analyses showed the six genes to be developmentally regulated and expressed during conidiation. The gene products of alb1 (for "albino 1"), arp1 (for "aspergillus reddish-pink 1"), and arp2 have high similarity to polyketide synthases, scytalone dehydratases, and hydroxynaphthalene reductases, respectively, found in the dihydroxynaphthalene (DHN)-melanin pathway of brown and black fungi. The abr1 gene (for "aspergillus brown 1") encodes a putative protein possessing two signatures of multicopper oxidases. The abr2 gene product has homology to the laccase encoded by the yA gene of Aspergillus nidulans. The function of ayg1 (for "aspergillus yellowish-green 1") remains unknown. Involvement of the six genes in conidial pigmentation was confirmed by the altered conidial color phenotypes that resulted from disruption of each gene in A. fumigatus. The presence of a DHN-melanin pathway in A. fumigatus was supported by the accumulation of scytalone and flaviolin in the arp1 deletant, whereas only flaviolin was accumulated in the arp2 deletants. Scytalone and flaviolin are well-known signature metabolites of the DHN-melanin pathway. Based on DNA sequence similarity, gene disruption results, and biochemical analyses, we conclude that the 19-kb DNA fragment contains a six-gene cluster which is required for conidial pigment biosynthesis in A. fumigatus. However, the presence of abr1, abr2, and ayg1 in addition to alb1, arp1, and arp2 suggests that conidial pigment biosynthesis in A. fumigatus is more complex than the known DHN-melanin pathway.

Amino Acid Sequence↗

PubMed1999

Basic fibroblast growth factor in experimental and clinical bacterial meningitis.

Basic fibroblast growth factor (bFGF), a neurotrophic factor in the CNS, is expressed at high levels in response to seizures or strokes. We examined the expression of bFGF during experimental bacterial meningitis and the levels of bFGF in the cerebrospinal fluid (CSF) of children with bacterial meningitis. For the experimental study, a mouse model of meningitis was established by intracranial injection of Streptococcus pneumoniae. Twenty-four hours after induced meningitis, the brains were sectioned and stained immunohistochemically for bFGF. Neutrophils and macrophages infiltrating the leptomeninges and the ventricles exhibited strong bFGF immunoreactivity. The neurons in the areas adjacent to the inflamed ventricles also showed enhanced bFGF expression. For the clinical study, we used an enzyme immunoassay to measure bFGF in CSF in 18 children with bacterial meningitis, 12 with aseptic meningitis, and 18 controls. The CSF levels of bFGF were twice as high in children with bacterial meningitis (medians 6.75-7.21 pg/mL) compared with those who had aseptic meningitis (2.9 pg/mL) or in control subjects (2.65 pg/mL, p < 0.0001, respectively). In patients with bacterial meningitis who survived, CSF bFGF decreased significantly after 24-50 h of antibiotic therapy (p < 0.0005). Patients who developed major sequelae or died had much higher levels of CSF bFGF than those without (134.9 pg/mL versus 7.38 pg/mL, p < 0.05). These findings of enhanced immunoreactivity of bFGF in experimental bacterial meningitis and an association of CSF levels of bFGF with disease severity in childhood bacterial meningitis suggest a biologic role for this neurotrophic factor in the pathophysiology of bacterial meningitis.

Animals↗

PubMed1999

Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics.

BACKGROUND: Previous reports concerning the effects of gender and age on steady-state plasma concentrations of clozapine and its major metabolites, norclozapine and clozapine-N-oxide, have been controversial. Since the frequency distribution of the plasma levels is asymmetrical and skewed to the right, the statistical methods (such as analysis of variance and regression analysis) used earlier are actually inappropriate for analyzing the effects of the variables on the concentrations and might contribute to the inconsistent results. The goal of the present study, with befitting statistics, is to measure the potential effect of dose, gender, age, and body weight on plasma levels of clozapine and its 2 major metabolites. METHOD: We retrospectively analyzed data from a therapeutic drug monitoring study for steady-state plasma clozapine, norclozapine, and clozapine-N-oxide levels that was conducted in a large group of Chinese schizophrenic inpatients (male:female ratio = 83:79; age range, 33.8 +/- 9.3 years). The daily doses of clozapine had ranged from 100 to 900 mg, with a mean +/- SD value of 379.5 +/- 142.2 mg. Plasma concentrations had been measured using high-performance liquid chromatography with ultraviolet detection. Multiple linear regression was adopted to quantify the effects of various factors on the plasma levels. The natural logarithm of the plasma level was used as the dependent variable to overcome the skewness problem. RESULTS: After adjusting the effects of gender, age, and body weight by multiple linear regression, each 1-mg increment in the daily dose could raise the clozapine level by 0.31%, norclozapine by 0.27%, and clozapine-N-oxide by 0.16%. Female patients had 34.9% higher clozapine levels and 36.3% higher norclozapine, with other variables being controlled. No sex differences were demonstrated for clozapine-N-oxide levels. Each 1-year increment in age would elevate the clozapine level by 1.1%, norclozapine by 1.0%, and clozapine-N-oxide by 1.0%. Body weight could not influence the levels of these compounds. CONCLUSION: The present results suggest that women possess higher plasma levels (about one third higher) of clozapine and norclozapine, but not the N-oxide metabolite. Each addition of 1 year in age elevated clozapine and either metabolite's levels by about 1%. Furthermore, every 1-mg increase in the daily dose raised clozapine and norclozapine concentrations by approximately 0.3%. These findings could assist clinicians in optimizing clozapine dosing strategies.

Adult↗

PubMed1999

Medium optimization for the production of antioxidants from Aspergillus candidus.

The objective of this study was to optimize the factors for the production of antioxidant from Aspergillus candidus CCRC 31543. Extracts of broth filtrate had higher antioxidant activity (inhibition of peroxidation [IP] >98%) when sucrose or lactose was used as a carbon source. Sucrose in the medium also resulted in a higher yield of extracts. Ethyl acetate extracts had the highest yield and antioxidant activity compared with the other two solvents. For the production of antioxidant, inorganic nitrogen sources were found to be more suitable than organic nitrogen sources, and ammonium sulfate was better than sodium nitrate. Yeast extract had a strong influence on the yield of antioxidant extracts. Both mycelium and broth filtrate of A. candidus CCRC 31543 showed similar antioxidant activity (IP = 95%), and they also had similar extraction yields.

Antioxidants↗

PubMed1999

The duration of ambulatory visits to physicians.

BACKGROUND: The objective of our study was to determine the typical length of ambulatory visits to a nationally representative sample of primary care physicians, and the patient, physician, practice, and visit characteristics affecting duration of visit. METHODS: We used an analysis of cross-sectional survey data to determine duration of visit and the characteristics associated with it. The data sources were a random sample of the 19,192 visits by adults to 686 primary care physicians contained in the 1991-1992 National Ambulatory Medical Care Survey, and the results of the Physician Induction Interview conducted by the National Center for Health Statistics. Duration of visit was defined as the total time spent in face-to-face contact with the physician. RESULTS: Mean duration of visit was 16.3 minutes (standard deviation = 9.7). Multivariate analysis allowed the calculation of the independent effect on visit length of a variety of characteristics of patients, physicians, organizational/practice setting, geographic location, and visit content. Certain patient characteristics (increasing age and the presence of psychosocial problems) were associated with increased duration of visit. Visit content was also associated with increased duration, including ordering or performing 4 or more diagnostic tests (71% increase), Papanicolaou smears (34%), ambulatory surgical procedures (34%), patient admission to the hospital (32%), and 3 preventive screening tests (25%). Reduced duration of visit was associated with availability of non-physician support personnel and health maintenance organization and Medicaid insurance. CONCLUSIONS: Multiple factors affect duration of visit. Clinicians, policymakers, and health system managers should take these considerations into account in managing physician resources during daily ambulatory practice.

Adult↗

PubMed1999

High-resolution computed tomography of pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a rare disease. It has been reported predominantly in Turkey. We report a case of PAM with characteristic high-resolution computed tomography (CT) findings. A 45-year-old Taiwanese woman had progressive difficulty in breathing for 7 years. Her chest radiographs showed diffuse high-density micronodules and reticular lines that obliterated the bronchovascular bundles and the margin of the heart and diaphragm. The micronodules were scattered throughout both lung fields with basal predominance. Examination of a transbronchial lung biopsy specimen showed PAM. High-resolution CT showed a unique and characteristic calcified reticular pattern and thickening of the interlobular septa of the lung parenchyma, with predominant basal and peripheral lung distribution. Reticulonodular changes of the interlobular septa and intralobular interstitial lines associated with subpleural air cysts and paraseptal emphysema were evident. These high-resolution CT findings are pathognomonic for PAM. Thus, lung biopsy may be avoided in the presence of this characteristic finding.

Calcinosis↗

PubMed1999

Interprotein disulfide bonds formed during isolation process tighten the structure of the postsynaptic density.

Postsynaptic densities (PSDs) isolated by biochemical means consist of a complex mixture of proteins that tightly bond to each other. The purpose of this report is to study whether the numerous interprotein disulfides found in the isolated PSDs contribute to the tight structure of the PSDs and whether these interprotein disulfides exist in vivo. PSDs were isolated from pig cerebral cortex by conventional methods except that iodoacetic acid (IAA) was added to all solutions to curtail the formation of disulfides during the isolation process. The PSDs thus isolated were fragmented easily by treatment with chaotropic reagents or ionic detergents, whereas the PSDs isolated in IAA-free solutions were resistant to these treatments. Electron microscopy revealed that the PSDs isolated in IAA-containing solutions were more fragmented than those isolated in IAA-free solutions. Furthermore, the PSD sample isolated in IAA-free solutions contained very large disulfide-linked aggregates that were virtually absent from the PSDs isolated in IAA-containing solutions. Our results suggest that the exceptionally tight structure of the PSDs isolated by conventional methods is due largely to the new disulfides formed during the isolation process and that the PSD proteins under in vivo conditions are held together primarily by noncovalent interactions.

Animals↗

PubMed1999

Alcohol metabolism and cardiovascular response in an alcoholic patient homozygous for the ALDH2*2 variant gene allele.

BACKGROUND: Alcohol metabolism is one of the biological determinants that can influence drinking behavior. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes involved in ethanol metabolism. Allelic variation of the ADH and ALDH genes can significantly affect vulnerability for the development of alcoholism. Homozygosity of the variant ALDH2*2 allele previously was believed to fully protect East Asian populations against the development of alcoholism. METHODS: Eighty Han Chinese alcoholics who met DSM-III-R criteria for alcohol dependence and 144 nonalcohol-dependent subjects were recruited and their data combined with data from 340 alcohol-dependent and 545 nonalcohol-dependent subjects described in an earlier report (Chen et al., 1999) to assess risk for alcoholism by logistic regression analysis. Genotypes of ADH2, ADH3, and ALDH2 were determined by polymerase chain reaction and restriction fragment length polymorphism. The ALDH2 genotype was confirmed by direct nucleotide sequencing. Blood ethanol concentration was determined by headspace gas chromatography and acetaldehyde concentration by high-performance liquid chromatography with fluorescence detection of the derivatized product. Cardiovascular hemodynamic parameters were measured by two-dimensional Doppler echocardiography and sphygmomanometry. Extracranial arterial blood flow was measured by Doppler ultrasonography. RESULTS: An alcohol-dependent patient was identified to be ALDH2*2/*2, ADH2*2/*2, and ADH3*1/*2. Following challenge with a moderate oral dose of ethanol (0.5 g/kg of body weight), the patient exhibited peak concentrations for ethanol (55.7 mg/dl) and acetaldehyde (125 microM). During 130 min postingestion, the patient generally displayed similar or even less intense cardiovascular hemodynamic alterations when compared to a previously published study of nonalcoholic individuals with ALDH2*2/*2 who had received a lower dose of ethanol (0.2 g/kg). Logistic regression analysis of the combinatorial genotypes of ADH2 and ALDH2 in 420 alcohol-dependent and 689 nonalcohol-dependent subjects indicated that risk for alcoholism was 100-fold lower for the ADH2*2/*2-ALDH2*2/*2 individuals than the ADH2*1/*1-ALDH2*1/*1 individuals. CONCLUSIONS: The gene status of ALDH2*2/*2 alone can tremendously but not completely (as thought previously) protect against development of alcohol dependence. Individuals carrying the combinatorial genotype of ADH2*2/*2-ALDH2*2/*2 are at the least risk for the disease in East Asians. Physiological tolerance or innate insensitivity to the accumulation of blood acetaldehyde following alcohol ingestion may be crucial for the development of alcoholism in individuals homozygous for ALDH2*2.

Adolescent↗

PubMed1999

Impact of magnetic resonance imaging on the advancement of medicine.

Magnetic resonance (MR) imaging has had a significant impact in many areas of modern medicine. Because of its good image resolution, tissue characterization, and functional assessment of various organs and systems, MR imaging has become an important modern technology in clinical practice and medical research. MR imaging has great flexibility in viewing anatomic structures in arbitrary imaging planes. With ultrafast MR imaging techniques, images of areas of interest can be obtained in a very short time, with elimination of physiologic motion artifacts. MR angiography obviates the need for catheterization and provides highly detailed images of the vascular anatomy, even of structures as small as the coronary artery. MR cholangiopancreatography provides results comparable to those of endoscopic retrograde cholangiopancreatography in many hepatobiliary diseases. Functional MR imaging is a new tool to evaluate physiologic function. MR spectroscopy has been used to explore the metabolic activity of normal and diseased organs and structures. The applications of MR imaging in clinical medicine and biomedical research are expanding.

Abdominal Neoplasms↗

PubMed1998

A single minute lesion around the ventral respiratory group in medulla produces fatal apnea in cats.

In 35 adult cats anesthetized with intraperitoneal chloralose and urethane, the ventrolateral medulla was explored by microinjection of kainic acid (KA, 24 mM, 200 nl) with metal electrode-tubing or glass micropipette to determine regions which elicit persistent apnea. Persistent apnea is defined as: (1) In spontaneously breathing cats, termination of respiration over 3 min with a decrease of the mean systemic arterial pressure (MSAP) to 25 mm Hg. (2) In animals under artificial ventilation and paralyzed by gallamine, cessation of bilateral phrenic nerve (PNA) activities over 25 min. The apnea producing area was located dorsal to the rostral pole of the lateral reticular nucleus, ventromedial to the ambiguous nucleus and immediately caudal to the retrofacial nucleus. Functionally, this region includes the rostral part of the ventral respiratory group (rVRG) encompassing the pre-BOtzinger area. We define this region as the VRG apnea producing area (VRG-Apa). Fatal apneusis was observed under following conditions: (1) Persistent apnea was produced after a single KA microinjection in one side of the VRG-Apa (5 animals). Microinjection of sodium glutamate (0.25 M, 70-200 nl) in the same area produced only brief apnea, while microinjection of kynurenic acid (0.1 M, 200 nl) showed little effect on the respiration but slightly increased the SAP. (2) Positioning an electrode nearby but not in the VRG-Apa with or without KA injection did not produce apnea. But when a second electrode insertion to the opposite VRG-Apa immediately produced persistent apnea even without KA injection (6 animals). (3) Midsagittal division of the medulla 0-5 mm rostral to the obex produced persistent silence of PNA on both sides in artificial ventilated animals (7 animals), while similar division 0-5 mm caudal to the obex (4 animals) produced a brief but reversible quiescence of PNA. In conclusion, findings of the present study support the existence of a restricted region of VRG-Apa. VRG-Apa on both sides are closely connected, and integrity of both VRG-Apa is essential for normal respiration.

Animals↗

PubMed1998

Alleviation of apoptosis by serum in Chinese hamster ovary cells ectopically expressing human Fas antigen.

Fas-mediated apoptosis is an important regulatory mechanism for the development of T-cells and prevention of oncogenesis. Here, we establish Chinese hamster ovary (CHO) cell lines which stably express Fas antigen, and analyzed apoptosis induced by anti-Fas IgM. While Fas-transfected hamster cells did not undergo apoptosis when stimulated with anti-Fas antibody in the presence of medium containing 10% serum, in reduced serum concentrations, anti-Fas antibody caused these cells to round up and detach from the culture dish. Analysis of the DNA content by a flow cytometry demonstrated a significant increase of cells with sub-G1 amount of DNA upon Fas stimulation in the low serum concentrations. The increase in the number of apoptosis cells was inhibited by an apopain (CPP32, caspase 3) inhibitor or insulin-like growth factor-I. In contrast, apoptosis in a Fas-transfected mouse T-cell line occurred in the presence of 10% serum. these results suggest that factors including insulin-like growth factor-I in fetal bovine serum protect CHO cells from apopain-dependent apoptosis mediated by Fas-antigen stimulation.

Animals↗

PubMed1998

Molecular and electrophysiological characterizations of fGluR3 alpha, an ionotropic glutamate receptor subunit of a teleost fish.

Here we report the cloning and functional analysis of a cDNA encoding a functional glutamate receptor subunit of Oreochromis sp., a freshwater teleost fish. The deduced amino acid sequence of this cDNA clone, fGluR3 alpha, displays the highest sequence identity to that of the mammalian GluR3 subunit. Results of quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis indicated that the expression level of fGluR3 alpha in the cerebellum was much less than that in the telencephalon and optical lobe. Similar to its mammalian counterpart, variants of fGluR3 alpha were created by alternative splicing and RNA editing at the R/G site. The channel properties of homomeric fGluR3 alpha expressed in Xenopus oocytes were similar to those of the mammalian alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-preferring receptors. The rank order of agonist potency of the expressed fGluR3 alpha is AMPA > or = glutamate > or = quisqualate > domoate > or = kainate. This is the first functional glutamate receptor of teleost fish being demonstrated to be sensitive to AMPA. Furthermore, this study suggested a strong functional conservation of AMPA-preferring receptors in vertebrates.

Amino Acid Sequence↗

PubMed1998

Virulence of catalase-deficient aspergillus nidulans in p47(phox)-/- mice. Implications for fungal pathogenicity and host defense in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare genetic disorder in which phagocytes fail to produce superoxide because of defects in one of several components of the NADPH oxidase complex. As a result, patients develop recurrent life-threatening bacterial and fungal infections. The organisms to which CGD patients are most susceptible produce catalase, regarded as an important factor for microbial pathogenicity in CGD. To test the role of pathogen-derived catalase in CGD directly, we have generated isogenic strains of Aspergillus nidulans in which one or both of the catalase genes (catA and catB), have been deleted. We hypothesized that catalase negative mutants would be less virulent than the wild-type strain in experimental animal models. CGD mice were produced by disruption of the p47(phox) gene which encodes the 47-kD subunit of the NADPH oxidase. Wild-type A. nidulans inoculated intranasally caused fatal infection in CGD mice, but did not cause disease in wild-type littermates. Surprisingly, wild-type A. nidulans and the catA, catB, and catA/catB mutants were equally virulent in CGD mice. Histopathological studies of fatally infected CGD mice showed widely distributed lesions in the lungs regardless of the presence or absence of the catA and catB genes. Similar to the CGD model, catalase-deficient A. nidulans was highly virulent in cortisone-treated BALB/c mice. Taken together, these results indicate that catalases do not play a significant role in pathogenicity of A. nidulans in p47(phox)-/- mice, and therefore raise doubt about the central role of catalases as a fungal virulence factor in CGD.

Acatalasia↗

PubMed1998

Subtypes and case-fatality rates of stroke: a hospital-based stroke registry in Taiwan (SCAN-IV).

Stroke data bank can afford important information regarding risk factors, pathogenesis, prognosis, etc. By means of hospital-based stroke registry, we investigated the risk factors and case-fatality rates in different types of stroke and transient ischemic attack (TIA) patients at the National Taiwan University Hospital in 1995. After excluding ineligible patients, 995 patients aged 1-98 years (575 men and 420 women) were recruited. Men predominated in all age groups for stroke and TIA in general except for cerebral hemorrhage (CH) in patients aged < 35 years and subarachnoid hemorrhage (SAH) in patients aged > or = 45 years. Of these, 676 (67.9%), 41 (4.1%), 228 (22.9%) and 50 (5%) patients were classified in the categories of cerebral infarction (CI), TIA, CH and SAH, respectively. The CI/CH ratio was 2.96. Hypertension remained one of the most important risk factors for CI, CH and TIA patients. Severe extracranial carotid artery stenosis (> or = 50%) was found in 12% of the CI patients and 27% of the TIA patients, but not found in the CH and SAH patients. Of these patients, the 30-day case-fatality rate was 10.9%, highest in SAH (30%), followed by CH (24.1%) and CI (5.6%). There were 41 in-hospital stroke patients who had significantly higher case-fatality rates than the other stroke patients (P<0.001 for all stroke, CI and CH patients by chi2 test). As compared to the previous stroke registries in Taiwan, there is a secular trend of increasing CI/CH ratios. These findings in Taiwan were compared with those in other populations, including other Asian, Caucasian and black populations. The CI/CH ratios in Asian populations, including Chinese, Japanese and Korean, were much lower than those in Caucasian and black populations. Dietary, environmental and genetic factors probably play important roles in these differences.

Adolescent↗

PubMed1998

Regional difference in epidermal thinning after skin denervation.

Denervation of skin has a profound influence on epidermis; epidermal thinning was a consistent finding in rats. However, it is not clear whether the degree of epidermal thinning was similar in the region receiving the same innervation. In mice, how early epidermal nerves were degenerated after nerve injury remained unknown. To address these issues, we transected the sciatic nerve in mice and compared the changes of epidermal thickness in different areas of the hind foot skin. Epidermal nerves degenerated within 48 h after nerve transection, similar to what was observed in rats. Seven days after nerve transection, there was differential thinning of epidermis. The interpad area, in the center of the sciatic nerve-innervated region, exhibited the most profound degree of epidermal thinning (34.6 +/- 3.1 vs 47.8 +/- 2.4 microns, P < 0.01). The heel area, in the periphery of the sciatic nerve-innervated zone, did not show significant thinning of epidermis after denervation (37.3 +/- 4.8 vs 41.5 +/- 5.1 microns, P > 0.05). The degree of epidermal thinning after denervation in the pad area was the intermediate one: with 98.8 +/- 4.8 vs 120.1 +/- 7.3 microns, P < 0.02, in the rete pegs, and 51.1 +/- 4.1 vs 62.1 +/- 6.0 microns, P < 0.02, in the dermal papilla. The differential thinning was obvious when the thickness of the denervated epidermis was normalized to that of the control epidermis with the ratios of 0.73 +/- 0.03 in the interpad area, 0.83 +/- 0.04 in the rete peg, 0.85 +/- 0.05 in the dermal papilla, and 0.92 +/- 0.05 in the heel. Epidermal thinning was reversed by reinnervation of the epidermis after sciatic nerve crush (41.5 +/- 1.5 vs 45.0 +/- 2.0 microns in the interpad area, P > 0.05). These findings suggest that sensory nerves exhibit trophic influences on the epidermis presumably through the effects of diffusible factors.

Animals↗

PubMed1998

In vitro evaluation of the cytotoxicity and genotoxicity of root canal medicines on human pulp fibroblasts.

An intracanal medicine is often required because microorganisms in the dentinal tubes may be difficult to eliminate completely by instrumentation. Phenolic compounds are widely used in dental treatment as sedatives for the dental pulp or as disinfectants for caries and the root canal. In this study, propidium iodide fluorescence and DNA precipitation assay were used to investigated the cytotoxic and genotoxic effects of camphorated phenol and camphorated parachlorophenol on cultured human pulp fibroblasts in vitro. Both medicines reduced the content of double-stranded polynucleic acid of fibroblasts over a 24-h culture period in a concentration-dependent manner. Camphorated parachlorophenol was more cytotoxic than camphorated phenol. But, both medicines did not cause genotoxicity on pulp cells. The advantage of these experimental methods are simplicity and rapidity. Furthermore, this experimental system may be useful for preliminary cytotoxicity and genotoxicity screening of various dental medicines in vitro.

Anti-Infective Agents, Local↗

PubMed1998

Risk factors analysis for early fatality in children with acute bacterial meningitis.

To identify the cause of early fatality and to delineate the clinical findings on admission associated with this early fatality, a retrospective study of 101 children with bacterial meningitis was performed in southern Taiwan. Risk factors for early fatality are compared between patients with and without acute death in the first 3 days after admission. The overall patient fatality is 27%. Eighty-five percent of them (23 patients) occur at an average of 16.5 hours after admission despite proper antibiotic treatment. The causes of early death are predominantly hemodynamic in 14 patients (61%) and predominantly neurologic in nine (39%). Analysis of clinical parameters available on admission indicated a significant risk of early death in patients who have tachycardia, tachypnea, hypothermia, poor skin perfusion, metabolic acidosis, leukopenia, thrombocytopenia, low cerebrospinal fluid leukocyte count, and high cerebrospinal fluid lactate level. Multivariate analysis demonstrates that metabolic acidosis, poor skin perfusion, and low cerebrospinal fluid leukocyte count are independently and significantly associated with early fatality. In conclusion, two thirds of early fatalities in children with bacterial meningitis are the result of septic shock. Close surveillance for signs of septic shock, as well as of brain herniation should be continued, especially within 3 days after antibiotic treatment.

Acute Disease↗

PubMed1998

Cytotoxic effect of pingyangmycin on cultured KB cells.

The antitumour antibiotic pingyangmycin (PYM; bleomycin A5) was isolated from many components of bleomycin (BLM) produced by Streptomyces pingyangensisn. PYM has a similar chemical structure to that of BLM but the terminal amine moiety is different. Therefore, it would be of significance to demonstrate the antitumour effect and action mechanism of PYM on cultivated tumour cells. In this study, we used the cell growth curve, plating efficiency, and DNA synthesis inhibition assay to demonstrate the cytotoxicity of PYM on cultured KB cells. In the meantime, the morphological variations of drug-treated cells were also observed. In addition, we used the DNA precipitation assay, a simple and rapid assay, for detecting DNA damage caused by PYM on cultured KB cells for potential genotoxicity. Our results indicate that the effect of PYM significantly inhibits the cell growth, colonyforming ability, and DNA synthesis of KB cells in a dose-dependent manner. Furthermore, when treated with 5 micrograms/ml of PYM for 24 h on cultured KB cells, DNA strand breaks can be induced (P < 0.05). Therefore, it is considered that the action mechanism of PYM is due to its ability to inhibit the synthesis of DNA and split the DNA chains.

Antibiotics, Antineoplastic↗