Biomedical subjects

G Kang

Publications and source records attributed to G Kang.

At least 19 recordsLinked to original sources

PubMed2001

Improved efficacy of chemotherapy for glioblastoma by radiation-induced opening of blood-brain barrier: clinical results.

PURPOSE: To improve the efficacy of chemotherapy for glioblastoma through the radiation-induced opening of the blood-brain barrier (BBB). METHODS AND MATERIALS: In two previous articles, we have described the results of brain scanning using technetium 99m-labeled somatostatin and the measurement of methotrexate (MTX) concentrations in blood and cerebrospinal fluid (CSF) after i.v. injection. We discovered that the BBB and blood-cerebrospinal fluid barrier opened to a certain extent after 20- to 40-Gy irradiation, thus increasing the degree to which MTX permeated the brain tissue. On the basis of these findings, we retrospectively analyzed the outcome in 56 patients with glioblastoma given either chemotherapy (CCNU) after 20- to 40-Gy irradiation (28 patients) or radiation therapy alone (28 patients). RESULTS: The 1-, 3-, and 5-year survival rates were 57.14%, 22.50%, and 15.00% in the combined-therapy group and 17.86%, 7.14%, and 3.57% in the radiotherapy alone group, respectively. The respective median survival times were 29.11 +/- 6.99 and 9.86 +/- 3.45 months (p < 0.001), which represented a statistically significant difference. CONCLUSION: Our study further confirms that opening of the BBB induced by irradiation with 20-40 Gy may optimize the effects of intracranial chemotherapy.

Adolescent↗

PubMed2001

cAMP-regulated guanine nucleotide exchange factor II (Epac2) mediates Ca2+-induced Ca2+ release in INS-1 pancreatic beta-cells.

1. The signal transduction pathway responsible for cAMP-dependent Ca2+-induced Ca2+ release (CICR) from endoplasmic reticulum Ca2+ stores was assessed in the insulin-secreting cell line INS-1. 2. CICR was triggered by the GLP-1 receptor agonist exendin-4, an effect mimicked by caffeine, Sp-cAMPS or forskolin. CICR required influx of Ca2+ through L-type voltage-dependent Ca2+ channels, and was blocked by treatment with nimodipine, thapsigargin, or ryanodine, but not by the IP3 receptor antagonist xestospongin C. 3. Treatment with the cAMP antagonist 8-Br-Rp-cAMPS blocked CICR in response to exendin-4, whereas the PKA inhibitor H-89 was ineffective when tested at a concentration demonstrated to inhibit PKA-dependent gene expression. 4. RT-PCR of INS-1 cells demonstrated expression of mRNA coding for the type-II isoform of cAMP-regulated guanine nucleotide exchange factor (cAMP-GEF-II, Epac2). 5. CICR in response to forskolin was blocked by transient transfection and expression of a dominant negative mutant isoform of cAMP-GEF-II in which inactivating mutations were introduced into the exchange factor's two cAMP-binding domains. 6. It is concluded that CICR in INS-1 cells results from GLP-1 receptor-mediated sensitization of the intracellular Ca2+ release mechanism, a signal transduction pathway independent of PKA, but which requires cAMP-GEF-II.

Animals↗

PubMed2001

A monkey model for enterohemorrhagic Escherichia coli infection.

Adult Macaca radiata (n=22) were infected intragastrically with 10(12) Escherichia coli O157:H7 strain 84-01, which produces Shiga toxins 1 and 2. Clinical symptoms and bacterial excretion were documented in each monkey for a specified time period before they were killed. At necropsy, samples were obtained for culture and histologic and ultrastructural examination. Seventeen monkeys had diarrhea: E. coli O157 was isolated from postinfection stool samples from all monkeys and from autopsy cultures for 14 of 22 monkeys. Histologic examination showed attaching-effacing lesions, which appeared at 12 h and persisted for 7 days, in 12 monkeys. Widening of the intercellular spaces, degeneration and vacuolization of the epithelial cells, epithelial tufting, extrusion of epithelial cells, and neutrophilic infiltration were characteristic features seen in 20 of the 22 infected monkeys but not in 4 control monkeys. This monkey model closely parallels the early stages of the disease produced by E. coli O157:H7 and would be useful in the further study of pathogenic mechanisms and prevention methods in enterohemorrhagic E. coli infections.

Animals↗

PubMed2001

Pathogenesis of rotavirus gastroenteritis.

The outcome of intestinal infection with rotaviruses is more complex than initially appreciated, and it is affected by a complex interplay of host and viral factors. Rotaviruses infect intestinal enterocytes, and the early events in infection are mediated by virus-epithelial cell interactions. Diarrhoea may be caused by several mechanisms including (i) malabsorption that occurs secondary to the destruction of enterocytes, (ii) villus ischaemia and activation of the enteric nervous system that may be evoked by release of a vasoactive agent from infected epithelial cells in the absence of significant pathologic lesions or enterocyte damage, and (iii) intestinal secretion stimulated by the intracellular or extracellular action of the rotavirus non-structural protein, NSP4, a novel enterotoxin and secretory agonist with pleiotropic properties. New studies of rotavirus infection of polarized intestinal epithelial cells show that rotaviruses infect cells differently depending on whether or not they require sialic acid for initial binding, and infection alters epithelial cell functions. NSP4 also affects epithelial cell function and interactions. NSP4 (i) induces an age- and dose-dependent diarrhoeal response in young rodents that is similar to virus-induced disease, (ii) stimulates a Ca(2+)-dependent cell permeability where the secretory response is age-dependent, and (iii) alters epithelial cell integrity. Antibody to NSP4 protects mouse pups from diarrhoea induced by homotypic and heterotypic viruses. These data support a new mechanism of rotavirus-induced diarrhoea whereby a viral enterotoxin triggers a signal transduction pathway that alters epithelial cell permeability and chloride secretion. This new information about how a gastrointestinal virus causes disease demonstrates common pathogenic mechanisms for viral and bacterial pathogens not previously appreciated. These results also suggest new approaches to prevent or treat rotavirus-induced diarrhoea.

Animals↗

PubMed2001

Epidemiological and laboratory investigations of outbreaks of diarrhoea in rural South India: implications for control of disease.

Two epidemics of acute, watery diarrhoea in villages in North Arcot district, India, were investigated. The attack rates were 10.03 and 15.53 per 100 population, the median duration was 5 days and enteric pathogens were present in 56.8% and 60.3% of specimens from the two villages, but no predominant pathogen was identified. Examination of stools from a 20% age-stratified random sample of the population of one of the villages after the epidemic found 22.9% of asymptomatic subjects excreted bacterial enteric pathogens. Despite the high background of enteric pathogen carriage, the isolation rates for shigellae, enteropathogenic Escherichia coli and Shiga-toxin producing E. coli were significantly higher (P < 0.001, P < 0.02, P < 0.05) during the epidemic. The epidemics may have been caused by faecal contamination of well water following rain. Point-of-use techniques for water disinfection may be most effective for preventing such outbreaks, but further research into the development of appropriate technology is required.

Adolescent↗

PubMed2001

Calculation of induced current densities for humans by magnetic fields from electronic article surveillance devices.

This paper illustrates the use of the impedance method to calculate the electric fields and current densities induced in millimetre resolution anatomic models of the human body, namely an adult and 10- and 5-year-old children, for exposure to nonuniform magnetic fields typical of two assumed but representative electronic article surveillance (EAS) devices at 1 and 30 kHz, respectively. The devices assumed for the calculations are a solenoid type magnetic deactivator used at store checkouts and a pass-by panel-type EAS system consisting of two overlapping rectangular current-carrying coils used at entry and exit from a store. The impedance method code is modified to obtain induced current densities averaged over a cross section of 1 cm2 perpendicular to the direction of induced currents. This is done to compare the peak current densities with the limits or the basic restrictions given in the ICNIRP safety guidelines. Because of the stronger magnetic fields at lower heights for both the assumed devices, the peak 1 cm2 area-averaged current densities for the CNS tissues such as the brain and the spinal cord are increasingly larger for smaller models and are the highest for the model of the 5-year-old child. For both the EAS devices, the maximum 1 cm2 area-averaged current densities for the brain of the model of the adult are lower than the ICNIRP safety guideline, but may approach or exceed the ICNIRP basic restrictions for models of 10- and 5-year-old children if sufficiently strong magnetic fields are used.

Biophysical Phenomena↗

PubMed2001

A prospective study of nosocomial enteric pathogen acquisition in hospitalized children in South India.

Screening for enteric pathogens in stool samples from 249 children under the age of 36 months, admitted to hospital for non-gastrointestinal disorders, was positive at admission in 41 (16.4 per cent) in a prospective study of enteric pathogen acquisition and diarrhoea in hospitalized children. Infection with multiple organisms was found in 31/41 (75.6 per cent) children who were positive when screened at admission. Of 194 children who had no enteric pathogens on admission and could be followed up for 3 days after discharge, clinical or laboratory data showed nosocomial enteric infections in 39 (20.1 per cent). Presumed nosocomial infection with more than one organism was seen in only two patients and no pathogens were isolated in 14 (35.8 per cent). Children presenting to hospital may asymptomatically carry enteric pathogens and potentially act as a source of nosocomial infections. One in five children admitted into hospital without an enteric infection is at risk of developing a nosocomial gastrointestinal infection, with rotavirus being the most common aetiological agent.

Chi-Square Distribution↗

PubMed2001

Consumer satisfaction at a child and adolescent state psychiatric hospital.

OBJECTIVE: This study examined satisfaction with services among patients in a child psychiatric hospital and their parents, and assessed the relationship between consumer satisfaction and the perception of improvement in the problem that led to hospitalization. METHODS: A consumer satisfaction survey developed by the investigators was administered to three sampling waves of child and adolescent psychiatric inpatients (N=157) and their parents or guardians (N=111). Ninety-five percent of patients contacted and 97 percent of their parents or guardians agreed to participate in the study. The survey provided data about the children's and parents' satisfaction with inpatient care and their perceptions of the children's clinical improvement. RESULTS: Most parents and children reported high satisfaction with patient care. Twenty-eight percent of children and 21 percent of parents reported some form of abuse by the staff during the hospital stay. Those who reported abusive behavior were significantly less satisfied with the hospital experience than those who did not report abuse. The participants' perception of clinical improvement was only weakly related to their satisfaction. CONCLUSIONS: Most child psychiatric patients and their parents will participate in consumer satisfaction surveys about inpatient care. Consumers are critical of a hospital if specific prompts in the survey are provided. An unexpectedly high level of consumer-reported abuse was found. Consumer-perceived clinical improvement was only weakly related to satisfaction.

Adolescent↗

PubMed2001

A common molecular machinery for exocytosis and the 'kiss-and-run' mechanism in chromaffin cells is controlled by phosphorylation.

Exocytosis and 'kiss-and-run' secretion coexist in chromaffin cells. Our findings suggest that these mechanisms are closely related, based on their common molecular machinery. Here we present a model that describes how chromaffin cells regulate catecholamine release by switching the mode of secretion between the two pathways, a process controlled by phosphorylation. Stimulation-dependent vesicle-plasma membrane interactions in chromaffin cells were analysed by simultaneous 'on-cell' capacitance and conductance measurements, a technique that allows the monitoring of single vesicles. Capacitance steps represent fusions of large dense-core vesicles with the plasma membrane, whereas capacitance flickers correspond to transient connections of the vesicle lumen with the extracellular space. All these events require the presence of extracellular calcium in millimolar concentrations. 'Kiss-and-run' type of release is enhanced by the kinase inhibitor staurosporine, which suggests that this secretion mode is regulated by protein phosphorylation. We also observed capacitance bursts, which most probably represent 'hot spots' of secretion and we found that 'kiss-and-run' is the prevalent mechanism during these episodes. The significance of 'kiss-and run' for neurohormone release is even higher at physiological temperature, because up to half of all secretion events are mediated by this mechanism.

Animals↗

PubMed2001

Currents induced in anatomic models of the human for uniform and nonuniform power frequency magnetic fields.

We have used the quasi-static impedance method to calculate the currents induced in the nominal 2 x 2 x 3 and 6 mm resolution anatomically based models of the human body for exposure to magnetic fields at 60 Hz. Uniform magnetic fields of various orientations and magnitudes 1 or 0.417 mT suggested in the ACGIH and ICNIRP safety guidelines are used to calculate induced electric fields or current densities for the various glands and organs of the body including the pineal gland. The maximum 1 cm(2) area-averaged induced current densities for the central nervous system tissues, such as the brain and the spinal cord, were within the reference level of 10 mA/m(2) as suggested in the ICNIRP guidelines for magnetic fields (0.417 mT at 60 Hz). Tissue conductivities were found to play an important role and higher assumed tissue conductivities gave higher induced current densities. We have also determined the induced current density distributions for nonuniform magnetic fields associated with two commonly used electrical appliances, namely a hair dryer and a hair clipper. Because of considerably higher magnetic fields for the latter device, higher induced electric fields and current densities were calculated.

Biophysical Phenomena↗

PubMed2001

[Induction and kinetic characterization of nitric oxide synthase in hepatocytes].

OBJECTIVE: To study the synergistic responses of nitric oxide synthase (NOS) induction in rat hepatocytes to LPS and various cytokines in vitro and the kinetic characteristics of iNOS. METHODS: The hepatocytes were isolated by in-situ pre-perfusion and collagenase circulatory perfusion of rat livers. The effects of LPS associated with IFN-r, TNF-alpha and IL-1beta or IL-6 on NOS activity, cGMP, and NO(2)(-)+NO(3)(-) were observed in hepatocytes, respectively. Also the kinetic characteristics of this enzyme and dose response of corticosteroids on the induction of iNOS were analyzed. RESULTS: The maximum induction of NOS activity was observed in hepatocytes treated by LPS in combination with IFN-r, TNF-alpha and IL-1beta or IL-6. The kinetic analysis of this iNOS demonstrated specific constants of Km=10.8 micromol/L, Vmax=263.2 pmol/min/mg protein(for L-Arg), and Ki of 0.56, 0.94 micromol/L for competitive inhibitor, L-NMMA and NNA, respectively. The time course of induction showed that iNOS activity peaked at 9 h; however, significant increase in release of NO(2)(-)+NO(3)(-) and cGMP sustained for at least 18 h. Dexamethasone and hydrocortisone dramatically inhibited the NOS induction in hepatocytes in vitro with IC50 of 3.5+/-10(-8)mol/L and 2.6+/-10(-6)mol/L, respectively. CONCLUSIONS: The expression of inductive NOS in hepatocytes requires specific synergetic action of cytokines, and the inducible characteristics may play an important pathogenesis in endotoxemia and septic shock.

Animals↗

PubMed2001

[Study on p53 gene mutation in hepatocellular carcinoma patients in China].

OBJECTIVE: To study p53 gene mutation in human hepatocellular carcinoma (HCC) samples and the relationship between p53 gene mutation and hepatitis B virus (HBV) infection. METHODS: DNA samples were prepared from 50 specimens of HCC patients that had been infected with HBV. Exons 5-9 were amplified with polymerase chain reaction (PCR), and then detected by single strand conformation polymorphism (SSCP). RESULTS: Over 26% (13/50) of p53 DNA samples were found to be mutated, mainly in exons 5-8 relating to 3,3,4,3 cases respectively and along with 4 suspicious samples. CONCLUSION: p53 gene mutation might be one of the causes of HCC, and HBV infection may be associated with such mutation in China.

Adolescent↗

PubMed2001

[Annexin V technique for the study of liver damage].

OBJECTIVE: To evaluate Annexin V technique for measuring hepatic apoptosis and to investigate the protective function of Rg1 and Rb1 on acute liver injury. METHODS: LPS-treated acute liver injury and the protective effect of Rg1 and Rb1 were assessed by Annexin V double staining and PI staining measurements. The activity of sPLA(2) was measured by [(3)H]-labelled oleic acid method. RESULTS: Annexin V showed a higher sensitivity and specificity than PI staining. It was only the Annexin V assay that could discriminate normal cells, apoptosis cells, and necrotic cells. Rg1 and Rb1 could reduce the percentage of hepatic apoptotic and necrotic cells (P<0.01) and activity of sPLA2 (P<0.01). CONCLUSIONS: The Annexin V assay is an ideal method for measuring apoptosis presently. Rg1 and Rb1 have a definite protective effect on acute liver injury in rats.

Animals↗

PubMed2001

Enteroaggregative Escherichia coli infection in a rabbit model.

Type strains of enteroaggregative Escherichia coli EAEC (17-2, serotype O3:H2; JM 221, serotype O92:H33), isolates from an adult and a child with diarrhoea and an asymptomatic colonised child were used to orally infect adult rabbits. The experimental animals were followed up and sacrificed at defined time periods. Colonisation of both small and large intestine was seen with all strains and isolates used. Isolates from an adult patient with diarrhoea (MP 27) and from an asymptomatic colonised child from the community (KM 1337) were recovered from the small intestine during the first week of infection and subsequently from the large intestine. A total of seven rabbits was infected with MP 27; while colonising the gastrointestinal tract of all seven rabbits, this isolate caused diarrhoea in only one. On ultrastructural examination, the rabbits infected with 17-2 showed invasion of lymphoid follicles. Bacteria were seen in intercellular spaces and within M cells, a finding that has not previously been described. It is clearly possible to produce gut colonisation by oral infection with EAEC in adult rabbits with normal flora.

Animals↗

PubMed2001

A study on some phenotypic virulence markers of enteropathogenic Escherichia coli.

BACKGROUND & OBJECTIVES: The problem of enteropathogenic Escherichia coli (EPEC) causing diarrhoea in infants exists in India. But often the enteropathogenic status is not based on adequate characterization. Hence there is a need for evaluating the serotyping being used to identify EPEC for its validity in the light of recent knowledge on phenotypic markers of virulence. This study was done to evaluate the EPEC isolates for two potential virulence factors namely entero-adhesiveness with subsequent actin accumulation and verotoxin production. METHODS: Fifty consecutive EPEC strains identified by serotyping from stool samples of children with diarrhoea during January 1997 to June 1999 were studied for HEp-2 cell adherence, the fluorescent actin staining (FAS) characteristics of Hep-2 cells and vero cytotoxin production. RESULTS: Serotypes O55, O125 and O126 accounted for most of the isolates. In the Hep-2 assay, 72 per cent of the strains showed localised pattern of adherence and 22 per cent showed a mixed pattern of localised and diffuse adherence. In the FAS test 96 per cent strains showed typical staining while none of the strains produced verotoxin. INTERPRETATION & CONCLUSION: 'O' serogrouping appears to be still the simplest and an useful test for presumptive identification of EPEC. The FAS test for confirmation of EPEC was found to be very consistent in indicating EPEC.

Animals↗

PubMed2000

Characterisation of rotavirus G9 strains isolated in the UK between 1995 and 1998.

G9P[6] and G9P[8] rotavirus strains were identified during 1995/96 through the molecular epidemiological surveillance of rotavirus strains circulating in the UK between 1995 and 1998. An increase in the incidence and spread of sporadic infections with rotavirus genotype G9P[8] across the UK was detected in the two following seasons. Partial sequencing of the VP7 gene showed that all the UK strains shared a high degree of homology and were related very closely to G9 strains from the US and from symptomatic infections in India (> or =96% homology). The UK strains were related more distantly to the apathogenic Indian strain 116E (85-87.8% homology). Phylogenetic analysis revealed clustering of the UK strains into 3 different lineages (I to III) and into two sub-lineages within lineage I. There were correlations between VP7 sequence clustering, the P type and the geographical origin of the G9 strains. Partial sequencing of the VP4 gene showed high degree of homology (>98%) among all the P[6] strains, and the sequences obtained from the P[8] strains clustered into 2 of the 3 global lineages described for P[8] strains associated with other G types. These data suggest that G9 strains may be a recent importation into the UK, and that G9P[8] strains may have emerged through reassortment in humans between G9P[6] strains introduced recently and the more prevalent cocirculating G1, G3 and G4 strains that normally carry VP4 genes of P[8] type.

Aged↗

PubMed2000

Familial intrahepatic cholestatic cirrhosis with positive antimitochondrial antibody: familial primary biliary cirrhosis.

We present three siblings (out of four) with intrahepatic cholestatic disease and cirrhosis. Two of the siblings, a 33-year-old woman and a 34-year-old man had advanced liver disease- with the liver histology showing established cirrhosis with chronic cholestasis and excess copper accumulation. Both died two years later due to hepatic encephalopathy. The third sibling, a 37-year-old man on routine check-up was found to have abnormal liver functions. The liver biopsy showed marked bile ductular proliferation with bridging fibrosis, reduction in interlobular bile ducts, and excess copper accumulation. The presence of antimitochondrial antibody in the serum in 1 in 320 dilutions in all three patients and 1 in 80 dilutions in the oldest healthy sibling and hypergammaglobulinemia in all the siblings confirmed the diagnosis of familial primary biliary cirrhosis. Antinuclear and smooth muscle antibodies were not present. Clinical and biochemical improvement has been noted in the third sibling after therapy with ursodeoxycholic acid.

Adult↗

PubMed2000

Rat hepatocellular apoptosis induced by glycodeoxycholate.

OBJECTIVE: To explore the relationship between glycodeoxycholate (GDC) and rat hepatocellular apoptosis. METHODS: GDC was used to treat rat hepatocytes cultured in vitro and the apoptotic cells were observed and analyzed with light microscope, transmission electron microscope, TUNEL in situ hybridization, DNA agarose gel electrophoresis and flow cytometry. RESULTS: When rat hepatocytes were incubated with GDC (final concentration of 100 micromol/L) for 2h, apoptotic hepatocytes were observed with light and transmission electron microscope, and TUNEL in situ hybridization. When the hepatocytes were incubated with GDC (final concentration of 50, 100, 150 micromol/L, respectively) for 2h, or with GDC (final concentration of 100 micromol/L) for 2, 4, 6, 8h, respectively, agarose gel electrophoresis of the hepatocytes DNA demonstrated the typical ladder patterns. CONCLUSION: GDC with final concentration of 50, 100, 150 micromol/L could induce rat hepatocellular apoptosis.

Animals↗