Evaluation of effective energy using radiochromic film and a step-shaped aluminum filter.

Although the half-value layer (HVL) is one of the important parameters for quality assurance (QA) and quality control (QC), constant monitoring has not been performed because measurements using an ionization chamber (IC) are time-consuming and complicated. To solve these problems, a method using radiochromic film and step-shaped aluminum (Al) filters has been developed. To this end, GAFCHROMIC EBT2 dosimetry film (GAF-EBT2), which shows only slight energy dependency errors in comparison with GAFCHROMIC XR TYPE-R (GAF-R) and other radiochromic films, has been used. The measurement X-ray tube voltages were 120, 100, and 80 kV. GAF-EBT2 was scanned using a flat-bed scanner before and after exposure. To remove the non-uniformity error caused by image acquisition of the flat-bed scanner, the scanning image of the GAF-EBT2 before exposure was subtracted after exposure. HVL was evaluated using the density attenuation ratio. The effective energies obtained using HVLs of GAF-EBT2, GAF-R, and an IC dosimeter were compared. Effective energies with X-ray tube voltages of 120, 100, and 80 kV using GAF-EBT2 were 40.6, 36.0, and 32.9 keV, respectively. The difference ratios of the effective energies using GAF-EBT2 and the IC were 5.0%, 0.9%, and 2.7%, respectively. GAF-EBT2 and GAF-R proved to be capable of measuring effective energy with comparable precision. However, in HVL measurements of devices operating in the high-energy range (X-ray CT, radiotherapy machines, and so on), GAF-EBT2 was found to offer higher measurement precision than GAF-R, because it shows only a slight energy dependency.

Half-value layer measurement: simple process method using radiochromic film.

Although the half-value layer (HVL) is one of the important parameters for QA and QC, constant monitoring has not been performed because the measurements using an ionization chamber (IC) are time-consuming and complicated. To solve these problems, the use of radiochromic film (GAFCHROMIC XR TYPE R: GAF-R) with step-shaped aluminum (Al) filters, referred to herein as the simple process method, has been developed. The measurement X-ray tube voltages were 120 kV, 100 kV, and 80 kV. The Al filter area, the full exposure area, and the unexposed area were set on the GAF-R so as to obtain correct data. The HVL was evaluated using the density attenuation ratio. The HVLs obtained using the GAF-R and an 1C dosimeter were compared. HVLs with X-ray tube voltages of 120 kV, 100 kV, and 80 kV using the GAF-R were 4.10 mm, 3.55 mm and 2.97 mm, respectively. The difference ratios of the HVLs using the GAF-R and the IC were 1.2%, 7.6%, and 10.0%, respectively. The HVL at 120 kV can be routinely and quickly measured using the simple process method. Therefore, an IC dosimeter is not needed for HVL measurements for QA and QC. However, the HVL measurements of low energy (100 kV and 80 kV) need attention.

Evaluation of effective energy for QA and QC: measurement of half-value layer using radiochromic film density.

The effective energy of diagnostic X-rays is important for quality assurance (QA) and quality control (QC). However, the half-value layer (HVL), which is necessary to evaluate the effective energy, is not ubiquitously monitored because ionization-chamber dosimetry is time-consuming and complicated. To verify the applicability of GAFCHROMIC XR type R (GAF-R) film for HVL measurement as an alternative to monitoring with an ionization chamber, a single-strip method for measuring the HVL has been evaluated. Calibration curves of absorbed dose versus film density were generated using this single-strip method with GAF-R film, and the coefficient of determination (r2) of the straight-line approximation was evaluated. The HVLs (effective energies) estimated using the GAF-R film and an ionization chamber were compared. The coefficient of determination (r2) of the straight-line approximation obtained with the GAF-R film was more than 0.99. The effective energies (HVLs) evaluated using the GAF-R film and the ionization chamber were 43.25 keV (5.10 mm) and 39.86 keV (4.45 mm), respectively. The difference in the effective energies determined by the two methods was thus 8.5%. These results suggest that GAF-R might be used to evaluate the effective energy from the film-density growth without the need for ionization-chamber measurements.

[Subtraction image for dynamic liver MRI using free breath-hold at functional residual capacity: a clinical trial].

PURPOSE: Dynamic liver MRI images have been obtained under expiration breath holding (BH). However, problems with obtaining reproducible liver positions often observed. This study investigated ways to improve the reproducibility of liver position on dynamic liver MRI. MATERIALS AND METHODS: After giving informed consent, 60 patients (32 males and 28 females, ages 33-85, median age 69) were examined by liver dynamic MRI under two types of BH. The BH phases were voluntary expiration (VE) phase without any explanations and functional residual capacity (FRC) phase after careful explanation was provided. Plain images, arterial phase images, portal phase images and parenchymal phase images were obtained. For statistical evaluation of reproducibility, the area of the 2nd or 3rd images from top of the liver was measured in each phase using a threshold value of half maximum. Misregistration areas were calculated by finding the remainder of the liver area in the plain-arterial (Pl-A) phase, arterial-portal (A-Po) phase, plain-parenchymal (Pl-Pa) phase. Contingency table analysis was done due to the misregistration was occurred or not. RESULTS: Misregistration of liver image on the VE and the FRC of three phase types were statistical significant on the Pl-A (p < 0.01), on the A-Po (p < 0.01) and on the Pl-Pa (p < 0.05), respectively. CONCLUSION: The FRC phase following careful explanation of the BH provided significantly improved reproducibility of liver position on dynamic liver MRI. Therefore, precise subtraction images could be obtained for routine clinical examinations without slice matching.

Dose distribution in pediatric CT head examination using a new phantom with radiochromic film.

Performing a detailed dose measurement is important to keep radiation doses during computed tomography (CT) examinations as low as reasonably achievable. To estimate in detail the dose distribution during pediatric CT examination of the head, a sheet roll CT dosimetry phantom (SRCT-P) with radiochromic film (RF) was developed. The dose distributions in the SRCT-P (diameters of 6 [premature baby], 10 [neonate], and 14 [infant] cm) were evaluated. The SRCT-Ps were made by rolling up flexible acrylic sheets (1.1 g/cm3). RFs were positioned every 5 mm along the radius at each SRCT-P, starting at 10 mm (center) and ending on the surface. The dose distribution along the z-axis at the center or on the surface showed a flat or wave pattern, respectively. When the mean surface dose at 10 cm diameter was taken as 100%, the mean surface doses at 6 or 14 cm diameters were 105 or 96%, respectively, and the mean center doses at 6, 10, and 14 cm were 109, 99, and 74%, respectively. The maximum-minimum doses and dose distribution of a CT examination can be measured separately by using the SRCT-P with RF.

Computed tomography phantom for radiochromic film dosimetry.

To evaluate in detail the dose distribution during computed tomography (CT), a sheet roll CT dosimetry phantom (SRCT-P) with a radiochromic film (RF) was experimentally developed. The SRCT-P was made by rolling up a vinyl chloride sheet in a cylindrical shape to arbitrarily select the SRCT-P diameter, dose measurement position, and depth. The SRCT-P centre core consisted of a plastic hose in which a 10 mm acrylic bar with a RF was inserted. To determine the availability of the SRCT-P, the surface and centre doses (at a 5 mm radius) at each SRCT-P diameter (6-16 cm; every 2 cm) were measured. The ratios of the centre-to-surface doses (D(centre)/D(surface)) systematically increased, from 80 to 111%, for decreasing SRCT-P diameters, between 16 and 6 cm, respectively. The centre dose approached the surface dose as the SRCT-P diameter decreased. To use a RF for a CT dose measurement, further detailed research and analysis is necessary. However, this study has shown that a SRCT-P is useful and beneficial for the measurement of the dose distribution during a CT examination.

Taxol resistance and its reversal by synthetic isoprenoids in human bladder cancer cell line.

PURPOSE: We investigated the mechanism of action of reversal agents for taxol-resistance in bladder cancers. MATERIALS AND METHODS: We isolated a taxol-resistant cell line (KK47/TX30) from a human KK47 bladder cancer cell line (KK47/WT). We characterized KK47/TX30 cells and screened reversal agents for taxol-resistance. RESULTS: KK47/TX30 cells exhibited approximately 700-fold resistance to taxol and cross-resistance to Vinca alkaloids and topoisomerase II inhibitors. Western blot analysis demonstrated P-glycoprotein (P-gp) overexpression in taxol-resistant cells. Drug accumulation and efflux studies showed that the decreased taxol accumulation in the resistant cell line was due to enhanced taxol efflux. We synthesized 31 isoprenoids based on the structure of N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine (SDB), which could completely reverse multidrug resistance (MDR) as shown previously. Among those examined, trans-N,N'-bis(3,4-dimethoxybenzyl)-N-solanesyl-1,2-diaminocyclohexane (N-5228) could completely reverse taxol-resistance in KK47/TX30 cells. Results of a structure-activity relationship study of isoprenoids suggested that the following structural features were important for overcoming taxol-resistance: (1) a basic structure of 8 to 10 isoprene units, (2) a cyclohexane ring or benzene ring within the framework, (3) two cationic sites in close proximity to each other, and (4) a benzyl group with 3,4-dimethoxy functionalities with moderate electron-donation. CONCLUSIONS: Taxol-resistance was primarily mediated by P-gp overexpression in KK47/TX30 cells. One of the synthetic isoprenoids, N-5228 could completely reverse taxol-resistance in KK47/TX30 cells.

Endoscopic treatment of a long fibroepithelial ureteral polyp.

A case is reported of a 30-year-old woman with a long fibroepithelial polyp in the middle ureter treated with the Ho-YAG laser endoscopically. She presented with an intermittent macroscopic hematuria and lower abdominal pain lasting for 1 year. The filling defect on urography occupying one-third of the ureter was migratory depending on the patient position. Transurethral flexible ureterorenoscopy showed a large pedunculated tumor with a small base at the middle ureter. About 1 month after the endoscopic irradiation of the Ho-YAG laser to the base of tumor, the tumor was spontaneously discharged and pathologic examination revealed it to be a fibroepithelial polyp without malignant component. Postoperatively, the patient remained asymptomatic and follow-up excretory urographs showed no abnormal findings.

An autoantibody cross-reactive to hepatitis C virus core and a host nuclear antigen.

GOR, an epitope borne by the amino acid sequence, GRRGQKAKSNPNRPL, is recognized by anti-GOR antibodies specifically found in patients with non-A, non-B hepatitis (NANBH). The epitope is not coded for by the hepatitis C virus (HCV), the presumed causative agent for NANBH, but by a single copy gene of the host. Anti-GOR antibodies, distinct from anti-HCV (c100-3) antibodies, were revealed to have dual specificities; they target both the presumed core gene product of HCV and a host component. This cross recognition is probably derived from homologous regions between the GOR epitope and a viral epitope on the core protein in HCV. It is therefore suggested that anti-GOR is an autoantibody induced by HCV infection. This may explain the autoimmune disease like aspect of NANBH pathogenesis.

Non-A, non-B hepatitis specific antibodies directed at host-derived epitope: implication for an autoimmune process.

A cDNA clone (GOR47-1) bearing an epitope with an aminoacid sequence GRRGQKAKSNPNRPL (GOR epitope) was isolated from the plasma of a laboratory chimpanzee infected with human non-A, non-B hepatitis (NANBH) agent. The epitope was not encoded by reported sequences of hepatitis C virus (HCV) but instead was coded for by a host cellular sequence. An enzyme-linked immunosorbent assay (ELISA) was developed for antibodies to the GOR epitope (anti-GOR). A patient with acute NANBH produced both IgM and IgG classes of anti-GOR in the acute phase of the illness, with concentrations of IgG class anti-GOR rising when anti-HCV became detectable. Anti-GOR was detected in serum from 59 (81%) of 73 patients with chronic NANBH, 40 (65%) of 62 with NANB liver cirrhosis, and 25 (63%) of 40 NANB patients with primary hepatocellular carcinoma, but in only less than 10% of patients with chronic liver diseases due to hepatitis B virus, alcohol, or an autoimmune disorder, and in only 2% of voluntary blood donors. Circulating HCV-RNA was detected by polymerase chain reaction (PCR) in most patients seropositive for anti-GOR but negative for anti-HCV. Detection of anti-GOR would therefore help in the diagnosis of NANBH and in reducing the occurrence of post-transfusion hepatitis.

[A case having initial onset of bronchial asthma, probably induced by prolonged mycoplasmal infection, accompanied with concurrent highly suspicious chlamydial infection].

A 37-year-old man who had had no allergic history was admitted to our hospital complaining of high fever, a dry hacking cough and dyspnea. Mycoplasma and Chlamydia mixed infection was diagnosed because of increased antibody titers to simultaneous Mycoplasma pneumoniae and Chlamydia psittaci, however only the Mycoplasma pneumoniae antibody titer was not decreased during the over six months. One month after the onset, bronchial asthma was diagnosed subsequently from for the clinical symptoms of wheeze and cough. Clinical studies of the dual infection and the possibility of Mycoplasma pneumoniae as the probable antigen of bronchial asthma were discussed.

Chondrosarcoma of the trachea. A case report and literature review.

The cytologic presentation of a case of chondrosarcoma of the trachea in a 72-year-old man is described. A mass detected on routine chest roentgenogram and defined by CT scan was used to make a touch imprint smear during partial tumor resection. The cytologic findings included round or polygonal cells with occasional binucleation, round hyperchromatic nuclei and prominent nucleoli, present in an amorphous pink-violet or light-blue background containing fragments of chondroid tissue. The histopathology was interpreted as a low-grade chondrosarcoma. Cartilaginous tumors of the trachea should be considered in the differential diagnosis of upper airway obstruction.

Nucleotide sequence of a cloned hepatitis B virus genome, subtype ayr: comparison with genomes of the other three subtypes.

The entire nucleotide sequence of genomic DNA was determined for hepatitis B virus (HBV) of subtype ayr, which had been derived from the blood of a Japanese asymptomatic carrier. The genome was 3215 nucleotides long, and differed in DNA sequence by 10% from that of subtypes adw or ayw, but by only 2% from that of subtype adr. Amino acid sequences coded for by the S, C, P and X genes, as well as by the pre-S region, closely resembled those of subtype adr, indicating that the evolution of HBV/ayr from HBV/adr was more recent than the differentiation of the other three subtypes. In the product of the S gene, the mutually exclusive subtypic determinants of the surface antigen, d and y, were associated with variation of amino acid residues at only the 68th and 122nd positions from the N terminus, in contrast to the variation at as many as seven positions for the other set of subtypic determinants, w and r. Sequences representing high local hydrophilicity in the product of the S gene were involved in subtypic variation, although such sequences in the pre-S region were shared by HBV genomes of the various subtypes. In particular, a hydrophilic sequence of 19 amino acid residues, coded for by the pre-S(2) region and implicated in the presumed hepatotropism of HBV, was possessed in common by HBV/adr, HBV/ayr and HBV/ayw, and differed in HBV/adw by only one residue at the 9th position. This amino acid sequence appears to be a promising candidate for a synthetic peptide vaccine.

Integration of region X of hepatitis B virus genome in human primary hepatocellular carcinomas propagated in nude mice.

Tissues of human primary hepatocellular carcinoma (PHC) from six patients infected with hepatitis B virus (HBV) were propagated in nude mice, as well as a strain of hepatitis B surface antigen-positive PHC (PLC/PRF/5). Integration of viral DNA into chromosomal DNA of tumour cells was evaluated by the capacity to hybridize with radiolabelled DNA probes, each representing fundamental parts of the HBV genome, that is S and C genes and regions pre-S and X. All PHC cells possessed region X integrated in their chromosomes. However, integration of the S gene, C gene and region pre-S was found in only six of the seven PHCs. Based on these findings, the integration of region X seems to be most closely associated with carcinogenesis in HBV infection.

Lack of detectable reverse transcriptase activity in human and chimpanzee sera with a high infectivity for non-A, non-B hepatitis.

A serum sample from a patient with hepatitis and samples from two experimentally infected chimpanzees, all with a high infectivity for non-A, non-B hepatitis, were tested for reverse transcriptase. Biopsy confirmed that the hepatocytes of the chimpanzees that received these sera contained the characteristic tubular structures associated with non-A, non-B hepatitis. None of these three sera revealed detectable enzyme activity. We have not been able to confirm the association of reverse transcriptase activity with non-A, non-B hepatitis reported recently.

A solid-phase enzyme immunoassay for the common and subtypic determinants of hepatitis B surface antigen with monoclonal antibodies.

Monoclonal antibodies were raised against the common (a) as well as subtypic determinants (d, y, w and r) of hepatitis B surface antigen (HBsAg). They were applied to subtyping HBsAg by sandwiching it between antibody against a fixed on a solid-phase support and antibody against one or other of d, y, w and r, linked to horseradish peroxidase. The assay was applied to evaluate antigenic specificities of the NIH and Japanese panels composed of 44 sera containing HBsAg particles of various subtypes. HBsAg particles of a hybrid subtype, adyr, were sandwiched between monoclonal antibody against d and that against y, thereby indicating that they possessed both d and y determinants on the selfsame particle. The expression of d and y determinants on hybrid HBsAg particles was much less than that on ordinary particles of adw, adr, ayw or ayr subtype.

Determination of the antibody to hepatitis B e antigen by the inhibition on electrophoresis of free e antigen.

A new method is described for the rapid and sensitive detection of the antibody to hepatitis B e antigen (anti-HBe) in serum. Twenty-five microliters of the test serum were incubated with 10 microliter of the purified small 'free' e antigen, and then the consumption of the added antigen was detected by the failure to precipitate with standard anti-HBe in counter-electrophoresis. When a total of 444 serums from asymptomatic carriers of hepatitis B surface antigen was tested for anti-HBe by this method, 348 (78.4%) were found to be positive with a detectability much higher than that of the passive hemagglutination method which detected the antibody in only 264 (59.5%) of the same serums.

Demonstration of two distinct antigenic determinants on hepatitis B e antigen by monoclonal antibodies.

Mice were immunized against hepatitis B e antigen (HBeAg) isolated from sera of asymptomatic carriers of hepatitis B virus. Their spleen cells were fused with mouse myeloma (NS-1) cells, and 5 clones of hybridoma cells secreting antibody against HBeAg (anti-HBe) were isolated. For the production of anti-HBe in large scale, cells were cultivated both in vitro and in the peritoneal cavity of ascitic mice. Although monoclonal antibodies produced by these clones showed a strong reactivity of anti-HBe in hemagglutination tests, individual monoclonal anti-HBe did not reveal any precipitin line in immunodiffusion. When 2 of the 5 monoclonal antibodies were mixed together, however, some combinations showed a precipitin line against HBeAg, whereas others did not. Utilizing solid-phase radioimmunoassay involving a number of combinations of monoclonal antibodies used for solid-phase and radiolabeling, the 5 antibodies were classified into 2 groups. Three of the anti-HBe antibodies were found to be directed to 1 determinant of HBeAg (determinant a); the remaining 2 to the other determinant (determinant b). Determinants a and b were detected on HBeAg in the serum, as well as on the polypeptide of 19,000 daltons (P19) derived from the nucleocapsid of hepatitis B virus. Monoclonal anti-HBe antibodies with different specificities may provide useful tools in delineating the antigenic structure of HBeAg and also in evaluating immune responses of the host directed to its subdeterminants.

Tubular forms of hepatitis B surface antigen bind with the nucleus of 22-nm spherical HBsAg particles.

Spherical hepatitis B surface antigen particles (HbsAg) of 22-nm diameter were treated with sodium dodecylsulphate in the absence of reducing agents, and their nuclei were exposed. Factors that interact with the nucleus of HbsAg were detected in the serum of HBsAg carriers who were seropositive for hepatitis B e antigen and identified as tubular forms of HBsAg. The other categories of hepatitis B antigen, Dane particles, and 22-nm spherical HBsAg did not bind with the nucleus of HBsAg. When tubular forms of HBsAg had been treated with a proteolytic enzyme, they lost the reactivity to bind with the nucleus of HBsAg. On the basis of the results obtained, tubular forms of HBsAg bear the receptor of protein nature for the nucleus of 22-nm spherical HBsAg. The receptor allows rapid determination of tubular forms by a haemagglutination method for the evaluation of their clinical and epidemiological implications.

Hepatitis B e antigen polypeptides isolated from sera of individuals infected with hepatitis B virus: comparison with HBeAg polypeptide derived from Dane particles.

Hepatitis B e antigen (HBeAg) occurs in the serum of individuals infected with hepatitis B virus both free and in association with IgG. Utilizing a succession of steps involving salt precipitation, affinity chromatography, ion-exchange chromatography and isoelectrofocusing, we isolated free and IgG-bound forms of HBeAg from the sera of infected individuals with an overall gain in specific activity of 3000-fold and 540-fold, respectively. Polypeptide profiles of purified HBeAg preparations were studied by SDS-polyacrylamide gel electrophoresis in the presence of 2-mercaptoethanol. Both free and IgG-bound preparations revealed polypeptides with mol. wt. of 15500 (P15.5) and 16 500 (P16.5), and HBeAg activity was detected corresponding to their positions. The HBeAg polypeptides (P15.5/16.5) derived from sera were physicochemically different from the two polypeptides with HBeAg activity (P19 and P45) liberated from Dane particle cores by the conventional method involving incubation with Nonidet P40 and 2-mercaptoethanol. However, when core particles were prepared in the presence of a proteolytic enzyme, in addition to Nonidet P40 and 2-mercaptoethanol, they gave rise to HBeAg polypeptides with mol. wt. of 31000 (P31) and 15 500. Furthermore, P31 split into P15.5 when heated at 100 degrees C for 2 min. On the basis of these results, P15.5 may be assumed to be the essential polypeptide bearing HBeAg activity in the serum and also in Dane particles.