Biomedical subjects
Publications and source records attributed to T Kozuka.
Cysticercosis is an infection resulting from the larval form of the pork tapeworm, and domestic infection is rare in Japan. We report a case of Cysticercus cellulosae cutis in a Japanese woman who was thought to be infected in an endemic area and offer a brief review of the literature.
RATIONALE AND OBJECTIVES: To investigate whether expiratory high-resolution computed tomography (HRCT) is more useful than inspiratory HRCT for the detection of early-phase diffuse alveolar damage. METHODS: Eleven anesthetized rabbits were scanned with both inspiratory and expiratory HRCT every 30 minutes during mechanical ventilation. Ten rabbits were killed after the detection of pulmonary abnormalities on both inspiratory and expiratory HRCT. The remaining rabbit was killed when the pulmonary abnormalities appeared only on expiratory HRCT. RESULTS: In four cases (36%), the abnormal findings were detected earlier on expiratory HRCT than on inspiratory HRCT. In seven cases (64%), the abnormalities appeared simultaneously on inspiratory and expiratory HRCT. In all 11 cases, the histopathological changes of areas with abnormal CT findings corresponded to the exudative or proliferative phase of diffuse alveolar damage. CONCLUSIONS: Expiratory HRCT has the potential to detect the abnormalities of diffuse alveolar damage earlier than inspiratory HRCT.
The aim of the present study was to assess the evolution of various computed tomographic (CT) findings of lymphocytic interstitial pneumonia (LIP) with determination of potentially reversible or irreversible features. The study included 14 patients with biopsy-proved LIP who had serial thin-section CT examination 4 to 82 months (median 13 months) apart. Initial and follow-up CT scans were evaluated independently and then directly compared with each other by two observers. The main parenchymal abnormalities on the initial CT scan consisted of ground-glass attenuation (n = 14), thickening of interlobular septa (n = 13), centrilobular nodules (n = 12), cystic airspaces (n = 10), and airspace consolidation (n = 4). On follow-up CT, nine patients improved, one showed no change, and four showed increased extent of disease. With the exception of cysts, the parenchymal opacities were reversible. On follow-up CT, new cysts were seen in three patients; these developed mainly in areas with centrilobular nodules on initial CT. Honeycombing was seen on follow-up CT in four patients; in three patients it developed in areas of airspace consolidation and in one patient it developed in an area with ground-glass attenuation on initial CT. The majority of patients with LIP improved on follow-up. However, airspace consolidation may progress to honeycombing and centrilobular nodules may precede cystic formation.
Expression of human papillomavirus 16 (HPV-16) oncogenes is markedly higher in cervical cancer cells than in precancerous cells, and the elevated expression is believed to be required for the malignant phenotypes. We compared cancer cell lines CaSki (with 200 to 400 copies of HPV-16 DNA per cell) and SiHa (with one to two copies of HPV-16 DNA per cell) for the E7 expression in cells and the enhancer-promoter activity of the isolated viral long control region (LCR). Although these parameters per cell were 10-fold higher in CaSki than in SiHa, the levels of the E7 mRNA and protein per HPV DNA copy were 10- to 20-fold higher in SiHa than in CaSki. Characterization of the isolated LCRs showed that, whereas the LCR from CaSki resembled the prototype in structure and activity, the LCR from SiHa, with a deletion of 38 base pairs, enhanced transcription from P97 as assayed by using a plasmid capable of expressing luciferase. The upregulation appeared to be due to removal of one of the silencer YY1-binding sites. Furthermore, we isolated and characterized LCRs from 51 cervical cancer patients' biopsies. Among them, one with a deletion including YY1-binding sites and the other with a substitution in a YY1-motif were found to enhance the transcription. These findings suggest that mutation affecting YY1-motifs in the LCR is one of the mechanisms enhancing the viral oncogene expression in the course of progression of cancer cells.
A respiratory gating technique was developed to allow computed tomography-guided needle biopsy of small pulmonary nodules. Twenty-three pulmonary nodules less than 15 mm in diameter underwent biopsy with the use of this technique. There were 14 true-positive, eight true-negative, and one false-negative result (diagnostic accuracy, 96%). The diagnostic accuracy for small nodules without this technique in a historical control was 69% (P: <.05).
OBJECTIVE: The purpose of this study was to determine whether acute parenchymal lung diseases can be differentiated on the basis of the pattern and distribution of abnormalities revealed on high-resolution CT. MATERIALS AND METHODS: High-resolution CT scans of 90 patients with acute parenchymal lung diseases (19 with bacterial pneumonia, 13 with mycoplasmal pneumonia, 21 with acute interstitial pneumonia, 18 with hypersensitivity pneumonitis, 10 with acute eosinophilic pneumonia, and nine with pulmonary hemorrhage) were independently assessed by two observers who had no knowledge of clinical or pathologic data. The observers recorded abnormalities, their first-choice diagnosis, and their degree of confidence in their first-choice diagnosis. RESULTS: The two observers made a correct first-choice diagnosis in an average of 55 (61%) of 90 cases. Correct first-choice diagnosis was made in 50% of cases of bacterial pneumonia, 62% of mycoplasmal pneumonia, 90% of acute interstitial pneumonia, 72% of hypersensitivity pneumonitis, 30% of acute eosinophilic pneumonia, and 28% of pulmonary hemorrhage. CT findings allowed distinction between infectious and noninfectious causes in 81 (90%) of 90 cases. CONCLUSION: High-resolution CT is helpful in the differential diagnosis of infectious from noninfectious acute parenchymal lung disease. However, high-resolution CT is of limited value in making a specific diagnosis.
Human bone marrow stroma (BST)-dependent myeloma sister cell lines MOLP-6 and MOLP-7 were established from the peripheral blood of a multiple myeloma (MM) patient with IgA kappa type MM (stage IIIB). The growth of the cell lines is constitutively dependent on BST cells; none of the cytokines tested nor the culture supernatant of the BST cells could support the growth. Both cell lines showed typical plasma cell morphology with abundant cytoplasm and one to four nuclei under Wright staining. The immunoprofiles of MOLP-6 and MOLP-7 correspond to that seen typically in primary MM cells: positive for cytoplasmic immunoglobulin (Ig) chains, a heavy and kappa light chains, CD9, CD28, CD40, CD44, CD45, CD56, and PCA-1; the cells were negative for surface Igs and various other B-cell, T-cell and myelomonocyte associated markers. Both cell lines also expressed adhesion molecules including HCAM (CD44), VLA-4 (CD49d/CD29), VLA-6 (CD49f/CD29), ICAM-1 (CD54), NCAM (CD56), LFA-3 (CD58) and L-selectin (CD62L). The doubling time of MOLP-6 and MOLP-7 was 48 and 168 hours, respectively. In addition to this growth characteristic, the maximum cell density of each cell line was obtained at 1.7 x 10(6) cells/ml and 9.7 x 10(5) cells/ml, respectively. The characteristics of each cell line may reflect intraclonal variation of the proliferative capacity. The MOLP-6 together with the MOLP-7 sister will be useful model systems for the investigation of the biology of myeloma.
Recently, there have been several reports describing patients with multiple myeloma complicated by consciousness disturbance due to hyperammonemia. Here we report a patient with multiple myeloma and hyperammonemia, who died after rapid progression of the disease. A 71-year-old man who had been diagnosed as having Bence Jones protein (kappa)-type multiple myeloma in 1996 was readmitted to our hospital in February 1997 because of worsening bone pain, renal dysfunction, and hypercalcemia. Bone marrow aspiration yielded an almost dry tap, and the bone marrow was found to be completely occupied by immature plasma cells. Although liver dysfunction was slight, the serum ammonia level was high and increased gradually. Despite treatment, the patient died due to cerebral embolism and progression of plasmacytic leukemia in October 1997. Peripheral blood sampled at the time of death showed a serum ammonia level of 204 micrograms/dl, and the myeloma calls were cultured using monolayered bone marrow stromal cells as feeder cells. This led to the successful establishment of a cell line. The level of ammonia in the supernatant was high, indicating that the cultured myeloma cells produced and released ammonia.
We report our experience with allogeneic peripheral blood stem cell transplantation (allo-PBSCT) following a nonmyeloablative conditioning regimen consisting of cytarabine (8 g/m2) and cyclophosphamide (120 mg/kg) in the treatment of 2 patients aged 50 and 55 years with refractory chronic myelomonocytic leukemia and chronic myeloid leukemia in accelerated phase, respectively. Our nonmyeloablative regimen was well tolerated by older patients at high risk of regimen-related toxicity by the conventional conditioning regimen but was immunosuppressive enough to achieve mixed chimerism. After allo-PBSCT, we monitored chimerism in these patients by fluorescence in situ hybridization using X- and Y-specific probes and polymerase chain reaction-based analysis of a variable number of tandem repeats. We found that full chimerism and graft-versus-leukemia (GVL) effects could be induced in these patients by donor lymphocyte infusions and withdrawal of posttransplantation immunosuppressive therapy. Our observations suggest that a nonmyeloablative conditioning regimen can establish mixed chimerism and that donor lymphocyte infusion may induce GVL effects in older patients at high risk of regimen-related toxicity.
Unlike other herpesviruses, Epstein-Barr virus (EBV) has not yet been shown to infect macrophages. Six macrophage cultures were isolated from normal and affected samples. Nested polymerase chain reaction revealed the existence of the EBV genome in all these macrophages. EBV latent genes expression in all cultures were detected by mRNA in situ hybridization and immunofluorescence staining. Some cultures also expressed EBV replicative-infection proteins, while in other cultures induction of these proteins was demonstrated. These findings are the first to show expression of several latent and replicative-infection genes of EBV in macrophages, indicating that EBV proliferates in macrophages.
The p53 mutation has been found only in 0-6% of cervical carcinomas. In light of recent studies demonstrating that mutation of p53 gene was found in over 20% of the patients with vulvar carcinoma, a disease of elderly women and a known human papillomavirus (HPV)-related malignancy, we analysed mutation of the p53 gene in 46 women with cervical carcinomas at the age of 60 or more (mean; 71 years, range; 60-96 years). The presence of HPV and its type were analysed by polymerase chain reaction (PCR)-based assay using the consensus primers for L1 region. Mutation of the p53 gene was analysed by PCR-based single-strand conformation polymorphism and DNA sequencing technique. Point mutation of the p53 gene was detected in 5 out of 46 (11%) cervical carcinomas: 1 of 17 (6%) samples associated with high-risk HPVs (HPV 16 and HPV 18) and 4 of 27 samples (15%) with intermediate-risk HPVs (P= 0.36) whereas no mutation was found in 2 HPV negative cases. The mutated residues resided in the selective sequence known as a DNA-binding domain. The immunohistochemistry revealed the overexpression in cancer tissues positive for p53 mutation. All of the observed mutations of the p53 gene were transition type, suggesting that the mutation may be caused by endogenous mutagenesis. Although falling short of statistical significance reduces the strength of the conclusion, data presented here imply that p53 gene mutation, particularly along with intermediate-risk HPV types, may constitute one pathogenetic factor in cervical carcinoma affecting elderly women.
BACKGROUND: Cyclosporine A (CYA) is an immunosuppressive agent which is being used in the treatment of an increasingly wide range of dermatologic diseases, but its use has been avoided in carriers of hepatitis C virus (HCV). METHODS: We administered small doses of CYA (maximum, 3 mg/kg/day) for a long time to treat dermatologic diseases in one HCV-antibody-positive patient with no HCV-RNA in the blood, one patient with a small amount of HCV-RNA in the blood, and two patients with large amounts of HCV-RNA in the blood. RESULTS: Skin lesions improved in all patients, but recurred upon complete or partial withdrawal of CYA. In the absence of HCV-RNA in the blood, or when only a small quantity of HCV-RNA was present in the blood, HCV-RNA load showed no apparent change. In one patient with a large blood HCV-RNA load, CYA dosage reduction was followed by increases in alanine aminotransferase (ALT) levels and decreases in blood HCV-RNA. Aggravation of hepatitis due to immunologic reactivation was suspected in this patient. CONCLUSIONS: The reduction of CYA dosage is a key element in the use of this agent for cutaneous diseases.
The objective of this study was to examine the feasibility of soft-copy (CRT) reading and suitable compression. Forty abdominal CT images with a space-occupying lesion (SOL) in liver and 40 normal images were selected for receiver-operating-curve (ROC) analysis. Each image was compressed by JPEG extended mode into 1/10 its original capacity, and then an expanded image was printed on film. Ten radiologists evaluated the presence of liver SOLs (primary and secondary tumors) on soft-copy (CRT) and hard-copy (film) images. Each radiologist reviewed four types of images (original and compressed hard-copy and original and compressed soft-copy images). Values of the area under the curve in the various ROC analyses were 0.858 (FILM) and 0.842 (CRT) for original images and 0.879 (FILM) and 0.846 (CRT) for compressed images. The results of ROC analysis showed better reading performance with hard-copy than soft-copy images, but the difference was not statistically significant. Compressed images showed a higher value (0.879) than original images (0.858), a difference that was statistically significant (p < 0.029) by the paired t-test but not by the jackknife method. The results indicate that soft-copy reading is a clinically acceptable alternative to hard-copy reading. We have had no difficulty in reading abdominal CT images compressed to 1/10 of the original size by the JPEG method. This study was supported in part by a grant from the Japanese Ministry of Health and Welfare.
PURPOSE: To test the feasibility of a system for intermittent irradiation synchronized with respiratory motion in a clinical setting. MATERIALS AND METHODS: A newly developed gate pulse controller that starts and stops irradiation at a chosen phase of the respiratory cycle by controlling a linear accelerator was used in six patients with lung cancer. A laser displacement sensor was used for the detection of respiratory motion. Three patients underwent radiation therapy during the cycles between 50% expiration and 50% inspiration (step 1), and three patients underwent radiation therapy during the cycles between 70% expiration and 30% inspiration (step 2). RESULTS: The system functioned well; irradiation was verified with portal verification radiography in all six patients. The range of the tumor position during synchronized irradiation was detectable with fast portal localization radiography. The treatment times for steps 1 and 2 were 1.38-1.71 and 2.03-2.18 times longer, respectively, than those for conventional irradiation. CONCLUSION: Synchronized irradiation with the authors' system allowed convenient and reliable reduction of the target volume. Further study is needed to standardize the system for clinical use.
PURPOSE: To evaluate radiation therapy regimens for improvement in local control in patients with limited-stage small cell lung cancer. MATERIALS AND METHODS: Radical radiation therapy results in 117 patients with limited-stage small cell lung cancer were retrospectively reviewed. The protocols in 90 patients were 40 Gy in 20 fractions (n = 28), 50 Gy in 25 fractions (n = 32), and 45 Gy in 30 fractions (accelerated hyperfractionation, n = 30). The other 27 patients received thoracic irradiation (dose range, 20-60 Gy; median dose, 54 Gy). All patients underwent systemic chemotherapy. RESULTS: The 5-year Kaplan-Meier survival rates in the patients with N0, N1, N2, and N3 disease were 26%, 34%, 18%, and 0%, respectively; the rates of in-field relapse were 25%, 36%, 26%, and 25%, respectively; and the rates of marginal relapse were 0%, 9%, 15%, and 29%, respectively. In 56% of patients with marginal relapse, the relapse site was at the upper margin. The 4-year in-field control rates for the patients who underwent 40, 50, and 45 Gy were 51%, 70%, and 56%, respectively. CONCLUSION: Patients with N3 limited-stage small cell lung cancer should undergo a separate protocol, and the upper margin should be extended in patients with N2 or N3 disease.
Dose distribution images play important roles in the management of cancer patients. To date hard copies of these images have been stored and referred to by radiation oncologists as needed. In most cases, these images were not available to medical personnel outside the radiation oncology department. We have developed a mechanism in the hospital to access these dose distribution images via WWW (World Wide Web). A screen snapshot of a dose distribution image on the CRT of a treatment planning machine is copied to the WWW server and converted to a GIF image. Similarly, we can register dose volume histograms and digitally reconstructed radiographs on the WWW. Medical personnel throughout the hospital can access the images through the WWW browser. As a result, radiation oncologists are given detailed information on target definition in treatment planning by expert physicians. The system also helps co-medical staff in understanding dose distributions and predicting radiation injuries. At the same time, it actualizes an electronic archive of dose distribution images, which is a database for quick and reliable review, evaluation and comparison of treatment plans. This technique also furthers a close relationship among radiation oncologists, physicians, and co-medical personnel.
The effectiveness of a hospital information system (HIS) and a radiological information system (RIS) was evaluated to optimize preparation for the planned full clinical operation of a picture archiving and communication system (PACS), which is now linked experimentally to the HIS and the RIS. One thousand IC (integrated circuit) cards were used for time studies and flow studies in the hospital. Measurements were performed on image examination order entry, image examination, reporting, and image delivery times. Even though after the HIS and the RIS operation only a small amount of time savings were realized in each time fraction component, such as in the patient movement time, examination time, and film delivery time, the total turn-around time was shortened markedly, by more than 23 hours on average. It was verified that the HIS and the RIS was beneficial in the outpatient clinics of the orthopedic department. Our method of measurement employing IC cards before and after HIS and RIS operations can be applied in other hospitals.
First, annual cost of electronic filing of medical images were calculated and compared with that of film storage in two hospitals under different conditions. Storage of medical images using a pixel size of 100 microns x 100 microns and 2-byte depth on the 130 mm, 650 MB magneto-optical disks costs with four times as much as the cost for film storage. However, 175 microns x 175 microns 12 bits combined with implementation of lossless compression would reduce the cost to a level equal to that for films storage. Doubled or tripled densities of MOD will improve the cost ever further. Second, the effectiveness of Hospital Information System/Radiological Information System (HIS/RIS) was evaluated. Examination time, film delivery time and the total turn-around time was markedly shortened by more than 23 hours on average. Our measurement method employing IC cards in pre-post HIS/RIS/PACS procedures is generally applicable to other hospitals. Third, to determine the optimal method of maximizing the efficacy of diagnostic imaging, 260 questionnaires were sent to the staff of 13 university hospitals. Every situation was described by both a radiologist and the physician who ordered the examination and received the reports and images. The level of technical efficacy and diagnostic accuracy of radiology strongly influenced the diagnostic thought processes of the physician.