Biomedical subjects

K C Young

Publications and source records attributed to K C Young.

At least 19 recordsLinked to original sources

PubMed2003

Is the voltage gate of connexins CO2-sensitive? Cx45 channels and inhibition of calmodulin expression.

The sensitivity of Cx45 channels to CO2, transjunctional voltage ( V(j)) and inhibition of calmodulin (CaM) expression was tested in oocytes by dual voltage clamp. Cx45 channels are very sensitive to V(j) and close with V(j) preferentially by the slow gate, likely to be the same as the chemical gate. With a CO2-induced drop in junctional conductance ( G(j)), both the speed of V(j)-dependent inactivation of junctional current ( I(j)) and V(j) sensitivity increased. With 40-mV V(j)-pulses, the tau of single exponential I(j) decay reversibly decreased by;40% during CO2 application, and G(j steady state)/G(j peak) decreased multiphasically, indicating that both kinetics and V(j) sensitivity of chemical/slow V(j) gating are altered by changes in [H(+)](i) and/or [Ca(2+)](i). CaM expression was inhibited with oligonucleotides antisense to CaM mRNA. With 15 min CO2, relative junctional conductance ( G(jt)/ G(jt0)) dropped to 0% in controls, but only by;17% in CaM-antisense oocytes. Similarly, V(j) sensitivity was significantly lessened in CaM-antisense oocytes. The data indicate that both the speed and sensitivity of V(j)-dependent inactivation of the junctional current of Cx45 channels are affected by CO2 application, and that CaM plays a key role in channel gating.

Animals↗

PubMed2003

Image features of true positive and false negative cancers in screening mammograms.

The location, tissue background and imaging characteristics of true positive and false negative screens of breast cancers have been studied. This data can aid decisions in optimizing the display of mammographic information with the objective of minimizing false negative screens. Screening mammograms for four groups of women were digitized; those with screen detected cancers, those with false negative interval cancers, and matched normals for both groups. The optical density (OD) distribution in the main breast region of each mammogram was determined. The OD in three regions of interest around the cancers was also measured. Cancer locations were mapped and warped onto a typical image to show their spatial distribution. Where a cancer was detectable by calcifications alone it had a relatively low probability of being a false negative interval cancer. The mean OD differences between the cancer and the cancer background region (excluding calcifications) were approximately a factor of two lower in dense breasts compared with other breast types. Poorly defined masses that became interval cancers had mean OD differences that were approximately a factor of 0.1 OD lower than those that were detectable by screening. 22% of false negative cancers were located near the chest wall edge of the mammograms compared with 10% of the true positives. The results indicate the importance of effectively displaying information in the lighter areas of the mammogram, corresponding to glandular tissues, with sufficient contrast for suspicious mammographic details to be detected. Where the mean OD differences between the cancer and its background region are low, as measured for some poorly defined masses, there is an increased risk of a false negative interval cancer. Particular attention should be given to the chest wall area of the film, especially in the lower retroglandular region, during routine screening.

Breast Neoplasms↗

PubMed2002

Clinical comparison of high-dose interferon-alpha2b with or without ribavirin for treatment of interferon-relapsed chronic hepatitis C.

BACKGROUND: Interferon a with ribavirin combination therapy is effective but still unsatisfactory in the treatment of patients with interferon-relapsed chronic hepatitis C. AIMS: To compare, in a randomized, double blind, placebo-controlled study, high-dose interferon-alpha2b with or without ribavirin in the treatment for interferon-relapsers. PATIENTS: A total of 52 patients with interferon-relapsed chronic hepatitis C were randomly assigned to receive 24-week treatment with interferon-alpha2b (6 MU three times per week) combined with either ribavirin (1,000 to 1,200 mg per day) or a matched placebo and then followed for an additional 24 weeks. METHODS: Hepatitis C virus RNA was detected by reverse-transcription polymerase chain reaction. For determining viral concentration, the commercial bDNA Quantiplex hepatitis C virus-RNA 2.0 assay was used. Genotyping was performed by reverse hybridization assay RESULTS: At the end of treatment, no detectable hepatitis C virus RNA levels were observed in 92% (24/26) of patients on interferon alpha2b/ribavirin and 81% (21/26) of patients on interferon alpha2b/placebo. At the end of the follow-up, a higher sustained virological response rate was seen in patients treated with interferon alpha2b/ribavirin than those treated with interferon alpha2b/placebo (69% vs 23%, p < 0.001). Patients with either initially high levels of viral concentration or with genotype 1 responded poorly. Patients who received interferon-alpha2b/ribavirin treatment and in whom no hepatitis C virus RNA was detected at 4th week after treatment had 90% chance to achieve sustained virological response. CONCLUSIONS: High-dose interferon-alpha2b plus ribavirin treatment is highly effective in interferon-relapsed patients.

Adult↗

PubMed2002

Radiation doses in the UK trial of breast screening in women aged 40-48 years.

Although data have been published on the radiation doses involved in screening women in the UK in the age range 50-64 years, data have not been published for the screening of younger women, when one might expect higher doses and a different risk benefit balance. Therefore, data on the radiation doses arising from screening younger women (age range 40-48 years) as part of the UK age trial have been collected and reviewed. Each of the screening centres participating in the trial was asked to submit measurements of doses for samples of approximately 50 or 100 women. The doses for 2296 women were received. The dose estimates were corrected to take account of variations in composition with age and breast thickness and in the spectra used. The average received dose was 2.5 mGy per oblique film and 2.0 mGy per craniocaudal film. Although these doses are about 7% higher than those calculated for the screening of older women, this was owing to differences in equipment rather than age of the women. Age itself was not found to be a significant factor affecting the dose to screened women aged over or under 50 years. An identifiable sub-group of women with larger breasts who were screened using higher dose systems received doses that were about 4.2 times the average, and should be considered in any risk benefit analysis. Where modern mammography systems with automatic beam quality selection and alternative target and filter materials had been introduced, there was a 15% reduction in average received dose and up to a 50% reduction in received dose for large breasts.

Adult↗

PubMed2001

Mitochondria regulate inactivation of L-type Ca2+ channels in rat heart.

1. L-type Ca2+ channels play an important role in vital cell functions such as muscle contraction and hormone secretion. Both a voltage-dependent and a Ca2+-dependent process inactivate these channels. Here we present evidence that inhibition of the mitochondrial Ca2+ import mechanism in rat (Sprague-Dawley) ventricular myocytes by ruthenium red (RR), by Ru360 or by carbonyl cyanide m-chlorophenylhydrazone (CCCP) decreases the magnitude of electrically evoked transient elevations of cytosolic Ca2+ concentration ([Ca2+]c). These agents were most effective at stimulus rates greater than 1 Hz. 2. RR and CCCP also caused a significant delay in the recovery from inactivation of L-type Ca2+ currents (I(Ca)). This suggests that sequestration of cytosolic Ca2+, probably near the mouth of L-type Ca2+ channels, into mitochondria during cardiac contractile cycles, helps to remove the Ca2+-dependent inactivation of L-type Ca2+ channels. 3. We conclude that impairment of mitochondrial Ca2+ transport has no impact on either L-type Ca2+ currents or SR Ca2+ release at low stimulation frequencies (e.g. 0.1 Hz); however, it causes a depression of cytosolic Ca2+ transients attributable to an impaired recovery of L-type Ca2+ currents from inactivation at high stimulation frequencies (e.g. 3 Hz). The impairment of mitochondrial Ca2+ uptake and subsequent effects on Ca2+ transients at high frequencies at room temperature could be physiologically relevant since the normal heart rate of rat is around 5 Hz at body temperature. The role of mitochondria in clearing Ca2+ in the micro-domain near L-type Ca2+ channels could be impaired during high frequencies of heart beats such as in ventricular tachycardia, explaining, at least in part, the reduction of muscle contractility.

Animals↗

PubMed2001

Coiled coil region of streptokinase gamma-domain is essential for plasminogen activation.

The specific functions of the amino acid residues in the streptokinase (SK) gamma-domain were analyzed by studying the interactions of human plasminogen (HPlg) and SK mutants prepared by charge-to-alanine mutagenesis. SK with mutations of groups of amino acids outside the coiled coil region of SK gamma-domain, SK(K278A,K279A,E281A,K282A), and SK(D360A,R363A) had similar HPlg activator activities as wild-type SK. However, significant changes of the functions of SK with mutations within the coiled coil region were observed. Both SK(D322A,R324A,D325A) and SK(R330A,D331A,K332A,K334A) had decreased amounts of complex formation with microplasminogen and failed to activate HPlg. SK(D328A,R330A) had a 21-fold reduced catalytic efficiency for HPlg activation. The studies of SK with single amino acid mutation to Ala demonstrate that Arg(324), Asp(325), Lys(332), and Lys(334) play important roles in the formation of a HPlg.SK complex. On the other hand, amino acid residues Asp(322), Asp(328), and Arg(330) of SK are involved in the virgin enzyme induction. Potential contact between Lys(332) of SK and Glu(623) of human microplasmin and strong interactions between Asp(328) and Lys(330), Asp(331) and Lys(334), and Asp(322) and Lys(334) of SK are noticed. These interactions are important in maintaining a coiled coil conformation. Therefore, we conclude that the coiled coil region of SK gamma-domain, SK(Leu(314)-Ala(342)), plays very important roles in HPlg activation by participating in virgin enzyme induction and stabilizing the activator complex.

Base Sequence↗

PubMed2001

Incidence, transmission, and clinical significance of hepatitis G virus infection in hemodialysis patients.

A high prevalence of hepatitis G virus (HGV) infection has been noted in patients receiving chronic hemodialysis (HD) therapy, yet the incidence rate and transmission route have rarely been reported. Serum samples from 160 chronically uremic patients in a HD unit were initially collected at the time chronic HD therapy was begun, and thereafter annually in July and, finally, in November 1999. Serum HGV RNA was detected using nested reverse transcription polymerase chain reaction, and HGV E2 antibody was determined using an enzyme immunoassay. Nucleotide sequences of the 5'-noncoding region were studied in the HD patients with HGV viremia. Forty healthy staff members were also enrolled as control subjects. Three of the 40 (7.5%) healthy staff members were positive for HGV RNA or HGV E2 antibodies, in contrast to 40 of the 160 (25%) HD patients, including 14 (8.8%) who were positive for HGV RNA only, 25 (15.6%) who were positive for HGV E2 antibody only, and 1 (0.6%) who had both markers. HGV exposure did not correlate with gender, age, duration of HD therapy, or history of blood transfusions. At least 20 of the 40 (50%) patients with HGV exposure had been infected before the start of chronic HD therapy. Nevertheless, at least nine (22.5%) patients acquired new HGV infections after starting chronic HD therapy, with an incidence rate of > or = 2.6% per year. Three patients with newly acquired HGV viremia after HD therapy was started and two with pre-existing HGV viremia before HD therapy was started had the same nucleotide sequences. HGV and HCV infections (with a prevalence of 14.4%) might have been transmitted independently in HD patients. In addition, HGV infection was not found to cause significant elevation of alanine aminotransferase levels in the group exposed to HGV. To conclude, the incidence of new HGV infections was at least 2.6% per year. In addition to transmission through blood transfusion, HGV may have been transmitted nosocomially patient-to-patient within the HD unit. The compliance with standard universal precautions should be carefully re-examined, but it is not necessary to routinely screen for HGV infection among patients on chronic HD.

Adult↗

PubMed2001

Limitations and improvements of the quantiplex branched-DNA assay in Hepatitis B virus-infected patients receiving lamivudine.

The branched DNA (bDNA) assay for hepatitis B virus (Chiron Corporation Emerville, USA) was investigated by application to HBV-infected patients in Taiwan, where the B and C genotypes of hepatitis B virus are most prevalent. The study group included sera with hepatitis B surface antigen (HBsAg) and e antigen (HBeAg); Group 1 (n=70) without treatment; Group 2 (n=28) lamivudine treatment less than 3 months; Group 3 (n=73) lamivudine treatment 3-12 months; Group 4 (n=45) HBeAg-negative sera after 1 year treatment with lamivudine; control group (n=36) HBsAg-negative sera. Comparison of identical-sample results showed a significantly higher coefficient of variation for low-level HBV DNA (<100 MEq/ml) than for high-level (> or =100 MEq/ml), indicating increasing assay inaccuracy uncertainty as the sample HBV DNA concentration decreased. It is thus concluded that low-titered sera should receive special careful pipetting and processing. It was also found that using the relative luminescence of the negative control plus two standard deviations (S.D.) as a new cutoff could promote sensitivity (97.1-->97.1%, 89.3-->100%, 76.7-->84.9%, and 17.8-->22.2% in Groups 1-4, respectively) and specificity (94.4-->97.2%). In summary, the bDNA HBV assay showed only moderate assay performance for samples with low HBV DNA levels. This problem can be improved partially by choosing a new cutoff value based on the relative luminescence of the negative controls in the kit.

Branched DNA Signal Amplification Assay↗

PubMed2001

Existence of hepatitis C virus in Culex quinquefasciatus after ingestion of infected blood: experimental approach to evaluating transmission by mosquitoes.

We used PCR to detect hepatitis C virus (HCV) RNA among supernatants of ground Culex quinquefasciatus mosquitoes that (i) had been fed HCV-positive blood, (ii) had been intrathoracically inoculated with HCV-positive blood, or (iii) were from homes of hepatitis C patients. HCV RNA was detectable under all three conditions, but it did not replicate in mosquitoes and was not detectably transmitted during feeding.

Animals↗

PubMed2001

Procedure for quantitatively assessing automatic exposure control in mammography: a study of the GE Senographe 600 TS.

The correct operation of a mammography system's automatic exposure control system (AEC) is essential if mammograms are to be produced with a suitable film exposure. A methodology has been developed that allows the performance of the AEC to be assessed quantitatively using clinical films. By digitizing mammograms, the mean optical density (OD) in the main breast region and in a region of interest corresponding to the position of the AEC detector are evaluated for each film, together with the area of the main breast. Using these data it is possible to determine the relationships between the mean OD, breast size and AEC detector position. The performance of the AEC on a GE Senographe 600 TS system was investigated. The study found that there is a tendency to underexpose smaller breasts, i.e. with an area less than approximately 4000 mm(2). This is equivalent to a compressed tissue width of approximately 60---80 mm. The difference in mean OD between the mammograms of small and large breasts was up to 0.7 OD. Provided the sensitive area of the AEC detector is known, this method of assessing AEC performance can be used with any mammography system.

Analog-Digital Conversion↗

PubMed2001

Implications of using high contrast mammography X-ray film-screen combinations.

The objective of this study was to determine the implications of using Fuji AD-M and Kodak min-R 2000, two high contrast X-ray film types developed for mammography. Evaluation of the Fuji AD-M film was divided into two parts. The first part was a contralateral comparison between mammograms using Fuji AD-M and Fuji UM-MA HC film-screen combinations. Fuji AD-M contrast was about 25% higher than that of Fuji UM-MA HC. The effect of increased contrast on image quality was investigated by visually grading the quality of information in different parts of each mammogram. Fuji AD-M film was generally judged to be better for overall diagnosis. However, 2.3% of mammograms produced using Fuji AD-M film were not acceptable and might have led to a technical recall of the patient. In the second part of this study, sets of mammograms from women attending mobile screening units were reviewed. One unit used Fuji AD-M film and the other used Kodak min-R 2000 film. Both samples of mammograms were digitized and analysed. The average film gradients between an optical density (OD) of 0.25 and 2.00 above base plus fog were 4.38 for Fuji AD-M film and 3.77 for Kodak min-R 2000 film. The main breast regions of the mammograms were judged to be satisfactorily displayed when breast tissues were above ODs of approximately 0.6 for Fuji AD-M film and 0.8 for Kodak min-R 2000 film.

Adult↗

PubMed2000

Incisional hernia after laparotomy: prospective randomized comparison between early-absorbable and late-absorbable suture materials.

Incisional hernia is a serious postoperative complication of laparotomy. Selecting an appropriate suture material may lessen such morbidity. This study undertook a prospective, randomized comparison of early-absorbable polyglactin 910 suture versus late-absorbable polydioxanone loop suture for fascial closure after abdominal surgery. A series of 340 consecutive patients undergoing elective laparotomy were randomized to have fascial closure with either polyglactin 910 suture or polydioxanone loop suture between October 1993 and August 1996. A 2-year follow-up revealed that 23 patients had died, and the overall mortality rate was 6.8% (23/340). Ten (10/340, 2.9%) patients, including seven with polyglactin 910 suture and three with polydioxanone loop suture, developed incisional hernias. The early postoperative evaluation revealed an incidence of wound infection of 4.1% (14/340). The development of incisional hernia was not secondary to postoperative wound infection in this study. Among these 340 patients, 192 had malignant diseases and 148 had nonmalignant ones. Fascial closure with polyglactin 910 suture was associated with more incisional hernias than that with polydioxanone loop suture, with marginal significance for patients in the malignant group (4.7% versus 0%, p = 0.07) but not in the nonmalignant group (2.6% versus 4.2%, p = 0.67). In conclusion, abdominal closure with a late-absorbable polydioxanone loop suture may be beneficial to patients with a malignant disease for preventing incisional hernia.

Abdomen↗

PubMed2000

GB virus-C/hepatitis G virus infection in a hepatitis C virus endemic village: prevalence in residents with low educational attainment and frequent recovery in females.

AIMS/BACKGROUND: GB virus-C/hepatitis G virus (HGV) is a newly identified flavivirus, which may share the same mode of transmission as hepatitis C virus (HCV). The aim of this study was to investigate associated factors of HGV infection and clearance in a HCV endemic village in southern Taiwan. METHODS: Five hundred and ninety-four residents of a village in southern Taiwan were enrolled for hepatitis virus screening. Clinical features were recorded and a questionnaire addressing the possible routes of transmission was filled in by the participating residents. RESULTS: The prevalence of antibody to hepatitis C virus and hepatitis B surface antigen in the 594 residents was 70.7% and 19.5% respectively. Of the 399 residents tested for HGV RNA, GB virus-C/Hepatitis G virus envelop 2 protein (HGV-E2) antibody, and HCV RNA, the prevalence was 13.5%, 25.3%, 53.1% respectively. Multivariate logistic regression analysis showed that low educational attainment was associated with HGV infection, old age and low educational attainment were associated with HCV infection, and female gender was associated with HGV clearance. Alanine aminotransferase (ALT) values were significantly higher for residents with HCV infection alone, HBV infection alone, and co-infection of HCV and HBV than for those without HBV, HCV, and HGV infection. There were no differences in ALT values between subjects with HGV infection alone and those without HBV, HCV, and HGV infections. Residents with co-infection of HGV and HBV, or HGV and HCV had ALT values similar to those with HBV or HCV infection alone. CONCLUSION: HGV infection is common in the HCV endemic village. The transmission of HGV is closely related to low educational attainment. HGV clearance is frequently encountered in females. Co-infection of HGV does not compound hepatocellular inflammation.

Adult↗

PubMed2000

Additional factors for the estimation of mean glandular breast dose using the UK mammography dosimetry protocol.

The UK and European protocols for mammographic dosimetry use conversion factors that relate incident air kerma to the mean glandular dose (MGD) within the breast. The conversion factors currently used were obtained by computer simulation of a model breast with a composition of 50% adipose and 50% glandular tissues by weight (50% glandularity). Relative conversion factors have been calculated which allow the extension of the protocols to breasts of varying glandularity and for a wider range of mammographic x-ray spectra. The data have also been extended to breasts of a compressed thickness of 11 cm. To facilitate the calculation of MGD in patient surveys, typical breast glandularities are tabulated for women in the age ranges 40-49 and 50-64 years, and for breasts in the thickness range 2-11 cm. In addition, tables of equivalent thickness of polymethyl methacrylate have been provided to allow the simulation for dosimetric purposes of typical breasts of various thicknesses.

Adipose Tissue↗

PubMed2000

Radiation doses received in the UK Breast Screening Programme in 1997 and 1998.

The mean glandular doses (MGDs) to samples of women attending for mammographic screening are measured routinely at screening centres in the UK Breast Screening Programme (NHSBSP). This paper reviews the data collected during screening in the NHSBSP in 1997 and 1998 for 23,752 films, using 171 X-ray sets, for 8745 women. Average MGD was 2.03 mGy per oblique film and 1.65 mGy per craniocaudal film, similar to the MGDs found previously in the NHSBSP for the years 1994 and 1995. MGD was found to increase with compressed breast thickness where the tube potential was selected manually, so that the average dose for 10 cm thick breasts was 2.7 times the average for all breasts. For large breasts (> 70 mm) the use of X-ray sets such as the IGE DMR, which automatically select the beam quality for each breast, resulted in lower doses compared with sets using manual tube potential selection. MGD to the standard breast was found to vary from 0.7 to 2.2 mGy and to be correlated with the average MGD per mediolateral oblique film for the women screened on that system (R = 0.79). No correlation between age and MGD was found within the invited age range of 50-64 years.

Age Factors↗

PubMed2000

Skin edge perception in mammograms: a comparison of two film-screen combinations.

The entire skin edge is not always seen on mammograms. The importance of demonstrating the full extent of the breast on a mammogram is uncertain, but there are implications for optimizing film design and use. The new Agfa HDR film has been designed to improve visualization of the skin edge without compromising overall contrast. A quantitative and qualitative comparison between Agfa HDR and the Fuji UMMA film has been performed. A total of 216 mammograms from 54 symptomatic women were analysed. For each view on each woman, one breast was imaged using Fuji UMMA film and the other using Agfa HDR film. The target density achieved on quality control films of PMMA blocks was 1.70 +/- 0.10 for both film types. A radiologist graded the skin edges of all the films as visible, just visible or dark. Measurements were made of the optical densities in the skin edge region and on the fully exposed black part of the film, adjacent to the skin line. 70% of the HDR films had visible skin edges compared with 43% of the UMMA films. 2% of the HDR films had dark skin edges compared with 26% of the UMMA films. Optical densities at the skin edge were broadly similar for the two films and in the range 3.6 +/- 0.3. However, the density of the black part of the Agfa film was about 0.5 higher than with the Fuji film and it appears that this was the main reason the skin edge region was better visualized with the Agfa film.

Female↗

PubMed1999

Analysis of optical density and contrast in mammograms.

The objective of this project is the development of tools for the UK NHSBSP to assess image quality quantitatively in clinical films, for the purposes of optimizing imaging procedures and audit. As an initial step, 120 mammograms of 46 women on a single day of screening were digitized and analysed to produce indices of optical density (OD) and contrast. Analysis was performed on three regions of interest (ROI): pectoral muscle, main breast and skin edge. Two radiologists independently graded the quality of information in the different parts of each mammogram, and categorized breast type as either "dense", "mixed density" or "fatty". Measurements of contrast and OD generally correlated well with the opinions of the radiologists. For the oblique mammograms, the mean OD in the main breast ranged between films from 1.25 to 2.24 with a mean of 1.69 +/- 0.02. In the craniocaudal mammograms, the mean OD in the main breast ROI ranged from 1.14 to 1.94 with a mean of 1.61 +/- 0.05. The OD for a quality control film of a 40 mm block of PMMA exposed on the same day with this system was 1.53. A contrast index (CI) was calculated for each mammogram as the difference between the points of maximum and minimum OD in the main breast. Mean CI was 1.02 +/- 0.09 for fatty breasts, 1.50 +/- 0.10 for mixed density breasts and 2.05 +/- 0.23 for dense breasts. A review of the radiologist assessments indicated that the main breast was satisfactorily displayed when glandular and fatty tissues were displayed within the OD range 0.8-2.9. An analysis of the dynamic range requirements showed that 17% of films had a dynamic range that lay above that calculated using the suggested OD limits.

Breast Neoplasms↗

PubMed1999

Plastic microchip electrophoresis for analysis of PCR products of hepatitis C virus.

BACKGROUND: Electrophoresis on polymeric rather than glass microstructures is a promising separation method for analytical chemistry. Assays on such devices need to be explored to allow assessment of their utility for the clinical laboratory. METHODS: We compared capillary and plastic microchip electrophoresis for clinical post-PCR analysis of hepatitis C virus (HCV). For capillary electrophoresis (CE), we used a separation medium composed of 10 g/L hydroxypropyl methyl cellulose in Tris-borate-EDTA buffer and 10 micromol/L intercalating dye. For microchip electrophoresis, the HCV assay established on the fused silica tubing was transferred to the untreated polymethylmethacrylate microchip with minimum modifications. RESULTS: CE resolved the 145-bp amplicon of HCV in 15 min. The confidence interval of the migration time was <3.2%. The same HCV amplicon was resolved by microchip electrophoresis in <1.5 min with the confidence interval of the migration time <1.3%. CONCLUSION: The polymer microchip, with advantages that include fast processing time, simple operation, and disposable use, holds great potential for clinical analysis.

DNA, Viral↗