Phase operator for the photon field and an index theorem.
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Biomedical subjects
Publications and source records attributed to K Fujikawa.
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To examine whether cell-to-cell interactions between human gingival epithelial cells (HGE) and periodontal ligament fibroblasts (PLF) or gingival fibroblasts (GF) take place in the periodontium, the effects on collagenase production by PLF and GF were analyzed after adding several concentrations of HGE-conditioned medium (HGE-CM) to PLF or GF culture. Collagenase production by both cell populations was stimulated by adding HGE-CM, which stimulated collagenase production by PLF to a greater extent than that by GF. The HGE-derived stimulatory factor had a molecular mass of approximately 20 kDa, and its stimulant effect was inhibited markedly in the presence of an anti-human interleukin-1 alpha (IL-1 alpha) neutralizing antibody, indicating that the factor was identical to, or antigenically cross-reactive with, IL-1 alpha. These results suggest that epithelial apical migration in the periodontium may occur after interstitial resident cells have released tissue-degrading enzymes, such as collagenase, and damaged the extracellular matrix, once a sufficient amount of IL-1 alpha-like factor for stimulating the production of proteolytic enzyme has been released by HGE in periodontal lesions.
The reproductive toxicity of iodixanol, a non-ionic isotonic contrast medium, was investigated in rats and rabbits. Iodixanol was administered intravenously to male rats at doses of 0.3, 1.0 or 2.0 gI/kg/day for 80 days or more until successful copulation. Female rats were treated with iodixanol at the same dose levels for at least 14 days prior to and in the early stage of pregnancy. No remarkable adverse effects on fertility were noted at any dose level. Increased water consumption and swollen paws/face were observed among male rats receiving > 1.0 gI/kg/day. In addition, decreased food consumption was observed in males of the 2.0 gI/kg/day group. In female rats, no remarkable adverse effects were noted at any dose level. Iodixanol elicited no evidence of teratogenicity when administered during the fetal organogenesis period to pregnant rats and rabbits at doses of 0.3, 1.0 or 2.0 gI/kg/day. No remarkable changes were observed in rat or rabbit fetuses, nor in dams of any dose group. In a perinatal and postnatal dosing study in rats using doses of 0.3, 1.0 or 2.0 gI/kg/day, iodixanol did not adversely affect the reproductive performance of the treated parent animals and pre- and postnatal development of their offspring.
In this study, we evaluated the osteoconductivity of calcium phosphate cement (CPC) as compared to that of a current hydroxyapatite-based material (AP) by implanting the materials in surgically formed defects in the jaws of dogs. One month post-operation, slight inflammatory reactions were observed in tissue areas adjacent to either CPC mass or AP. Three months after operation, the CPC mass-filled defects were covered with periosteum and bone tissues. The CPC mass in the defects was partially replaced by newly formed bone. In bone defects filled with AP, most of the interparticle space was filled with connective tissues including bone tissues. Six months post-operation, the CPC mass-filled defects were covered with periosteum and new bone, and most of the CPC mass was replaced by bone. Interparticle spaces of AP were filled with connective tissues and bone tissues.
BACKGROUND: Histological grading, especially the Gleason Score (GS), is considered to be of value in determining the prognosis of patients with prostate cancer. However, subjective histological grading is characterized by low reproducibility. On the other hand, estimate of Mean Nuclear Volume (MNV), which was developed by Gunderson and Jensen based on a sterological technique, is a very easy method with high reproducibility. Furthermore, it had been reported that MNV provides accurate prognosis of bladder cancer. In this study we compared MNV with two histological grading methods in determining the survival of prostate cancer. METHOD: A retrospective, prognostic study of 49 patients with prostate cancer diagnosed by Transurethral Resection of the Prostate (TUR-P) or Needle punch biopsy between Jan. 1983 and Jul. 1994 was performed. Unbiased estimates of MNV were compared with age at the time of diagnosis, clinical stage, histological grading according to, the general rules for clinical and pathological studies on prostatic cancer of the Japanese Urological Association (J.U.A.) and GS on the prognostic value. RESULTS: Although age at the time of diagnosis, J.U.A. classification and GS had no value as prognostic criteria, clinical stage (p = 0.0018) and MNV (p = 0.0087) correlated significantly with survival of prostate cancer. CONCLUSION: Results of this study indicate that estimates of MNV and clinical stage are prognostically superior to age at the time of diagnosis and morphologic grading of malignancy, such as J.U.A. classification and GS, in prostate cancer.
We studied the early detection of alloxan-induced pulmonary injury by magnetic resonance imaging in vivo. Permeability edema was induced in ten rats by intravenous injection of alloxan at 100 mg/kg. T1-and T2-weighted images were acquired in five rats every 30 min for 120 min after alloxan injection. Five rats served as controls. The rats were sacrificed immediately after imaging and examined microscopically. CT images were also acquired in five rats every 30 min for 120 min after alloxan injection. Five rats served as controls. The rats were sacrificed immediately after imaging, and the wet-to-dry ratio of the lung was measured. In T1-weighted images, relative signal intensity from the lung with permeability edema rose from 30 min to 120 min, and was greater than that from normal lung every time. In T2-weighted images, there was no statistically significant difference in relative signal intensity of the lung between permeability edema and the control during 120 min. In CT images, there was also no statistically significant difference in lung density between permeability edema and the control during 120 min. There was no statistically significant difference in the wet-to-dry lung ratio between edematous lung and normal lung. In histological study, mild congestion and interstitial edema were observed in edematous lung. These results suggest the potential capability of MR imaging in detecting the early phase of permeability pulmonary edema.
PURPOSE: Grading of malignancy in prostate cancer is based on qualitative, morphological examination and suffers from poor reproducibility. On the other hand, estimating the volume weighted mean nuclear volume, which was developed by Gunderson and Jensen based on a stereological technique, is a simple method with high reproducibility. Furthermore, it has been reported that mean nuclear volume is remarkably correlated with prognosis of bladder cancer. We compared mean nuclear volume to 2 histological grading methods and clinical stage to determine the prognosis of prostate cancer using a Cox proportional hazards model. MATERIALS AND METHODS: A retrospective, prognostic study of 52 patients with prostate cancer diagnosed by transurethral resection of the prostate or needle punch biopsy between January 1983 and July 1994 was performed. Unbiased estimates of mean nuclear volume were compared to patient age at diagnosis, clinical stage, histological grading according to the World Health Organization (WHO) classification and Gleason score of the prognostic value. RESULTS: Univariate analysis revealed that estimates of mean nuclear volume (p = 0.0011), clinical stage (p = 0.0014) and WHO classification (p = 0.0010) correlated significantly with progression-free survival, and that clinical stage (p = 0.0005) and estimates of mean nuclear volume (p = 0.0049) correlated significantly with disease-specific survival of patients with prostate cancer. However, multivariate analysis revealed that only estimates of mean nuclear volume and clinical stage were the 2 most powerful independent prognosticators in progression-free and disease-specific survival. CONCLUSIONS: Our results indicate that estimates of mean nuclear volume are prognostically superior to morphological grading of malignancy, such as Gleason score and WHO classification, in prostate cancer.
To evaluate the usefulness of MRA in the diagnosis of peripheral pulmonary nodules, 18 lung cancers and 12 old inflammatory nodules were studied employing multiplanar fast radiofrequency spoiled gradient echo sequence (SPGR) with phased array coils. For each case, 12 images in coronal and sagittal sections were obtained after administration of Gd-DTPA, and original images, maximum intensity projection (MIP) images and multiplanar reconstruction (MPR) images were used for the interpretation. In ten cases, MRA images were compared with resected specimens and we found that the minimum diameter of pulmonary vessels which could be demonstrated by our method was about 1.5mm. As the results of the interpretation of MRA images in 30 cases, venous involvement, which is one of the classical important findings indicative of malignancy, was clearly demonstrated in 15 of 18 (83%) lung cancers, whereas such involvement was detected in only 3 of 12 (25%) inflammatory nodules. Pulmonary MRA, especially MIP and MPR images could make it easy to identify involved vessels, and proved to be useful in differentiating pulmonary nodules.
We developed and implemented computerized patient management problems (CPMP) for medical school education as a simulation of case management and evaluated its efficacy in the School of Medicine at Chiba University. PMP was first developed in the USA; it was used for examinations by the board of American College of Physicians and then introduced to Japan for examination purposes. This test is a practical clinical test for decision making in various medical situations. PMP is, however, a kind of case simulation from a doctor's point of view; it is also a sophisticated tool in training medical students. PMP had many disadvantages in the past, but by computerizing PMP, we solved many problems. We developed the CPMP system for bedside teaching and evaluated its efficiency in terms of education by giving the same test twice and analyzing a survey.
A MAb 9F6 was capable of staining HPV16 E7 in a human cervical carcinoma line, CaSki, and rat 3Y1 cells stably expressing HPV16 E7 gene. Contrary to the current understanding of E7 as a nuclear protein, the site of staining was clearly cytoplasmic. The subcellular localization of E7 was further studied by using the beta-galactosidase (beta-gal) receptor method. A fusion protein composed of E7 and beta-gal was stably expressed in rat 3Y1 cells. The beta-gal activity in these cells was detected mostly in the nucleus, even though 9F6 still stained the cytoplasm of these cells. The fusion protein was also found to be oncogenic since transfected 3Y1 cells acquired transformed phenotypes such as increased saturation density and anchorage-independent growth. These results indicate that biologically active E7 exists mostly in the nucleus, but nuclear E7 is masked from 9F6. A series of deletion mutants of E7 further demonstrated that the amino acid sequence from 16 to 41 was enough to transport beta-gal into the nucleus. A mutation either at amino acid 24 or 26 which is known to disrupt the binding of E7 to RB, the retinoblastoma gene product, did not strongly affect the nuclear localization of the fusion protein, suggesting that the nuclear transportation of E7 is mostly independent of RB binding.
Annexin V is a human phospholipid binding protein (M(r) 36,000) that binds with high affinity to activated platelets in vitro. We studied the biodistribution and thrombus binding of annexin V in rabbit and swine models of fully occlusive arterial thrombi formed 1-2 h prior to injection of annexin V. Iodinated annexin V was cleared from blood in a rapid early phase (t1/2 = 6.4 min, 76% of radioactivity) and a slower late phase (t1/2 = 71 min, 24% of radioactivity). Organ uptake was highest in the kidney and spleen and lowest in heart and skeletal muscle. Thrombus/blood uptake ratios were (mean +/- SEM): 6.39 +/- 1.80 for rabbit iliac artery, 6.97 +/- 1.45 for swine carotid artery, and 7.68 +/- 1.70 for swine femoral artery (all p values < 0.01 versus control artery); a control protein, ovalbumin, showed an uptake ratio of 0.59 +/- 0.08 in swine femoral artery thrombi. These results indicate that annexin V is useful as an agent for selective targeting of platelet-containing thrombi.
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The expression and extracellular release of transferrin receptor (TR) was investigated by in vitro model system of erythroid differentiation. Human peripheral blood mononuclear cells were cultured with interleukin-3 (IL-3) for 7 days, and with erythropoietin (EPO) for an additional 8 days. After EPO stimulation, IL-3-stimulated blastic cells were serially differentiated into mature erythrocytes. [3H]-thymidine incorporation of cultured cells increased linearly from day 0 to 5, followed by a decrease. Flow cytometric analysis showed an increase of TR expression from day 0 to 5, followed by a slight decrease. By metabolic labeling with [35S]methionine and immunoprecipitation, the cell lysate exhibited a 95-kD band corresponding to the intact TR on sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography at day 5, when polychromatic erythroblasts had their peak. The culture supernatant solubilized by tween-20 exhibited a 95-kD and an 85-kD band on days 5 and 8, which corresponded to the intact and the truncated forms of TR, respectively. The 95-kD band was more intense at day 5 than at day 8. The reverse transcriptase-polymerase chain reaction assay showed that the receptor-mRNA expression was parallel to receptor synthesis. Thus, the synthesis and expression of TR on erythrocytes is associated mainly with cell proliferation in the early phase, and with both cell proliferation and hemoglobin production in the middle to late phases of maturation. Concomitantly, the extracellular release of TR from erythrocytes occurs in the middle to late phases of maturation. These data suggest that polychromatic erythroblasts release soluble TR as both intact and truncated forms and may be an important source of serum TR implicated as an index for erythropoietic activity in the marrow.
DNA polymerase beta (pol beta) cDNA of rat fused to an enhancer-promoter region plus a poly(A) signal sequence of actin 5C gene of Drosophila (abbreviated pol beta) was transferred to the Drosophila genome. Three of four constructed transgenic strains possessing transgene pol beta on different chromosomes were studied. Levels of the pol beta transcript and those of the polymerization activity of pol beta were markedly elevated in cultured cells transfected with pol beta-bearing vectors as well as in embryos of the transgenic strains. The popular idea that DNA polymerase beta participates in DNA repair was not supported by the observation that a pair of a normal and a pol beta strain, and the other pair of a mei-9 mei-41 (DNA-repair deficient double mutations) strain and a pol beta mei-9 mei-41 strain, showed no difference in survival within each pair after treatment with ultraviolet light, methylmethane sulfonate and mitomycin C. The other idea that DNA polymerase beta participates in recombination was supported by the findings that spontaneous frequency of recombination, either meiotic or mitotic, is significantly higher in a transgenic pol beta strain than in a non-transgenic strain. The enhanced recombination frequency in the pol beta strain may, however, reflect an indirect effect of over-produced pol beta proteins on chromosomal stability. Whatever the direct effect of rat pol beta is, the transgenic pol beta flies will be useful for study of the physiological role of pol beta and the mechanism of recombination.
Six Japanese patients in Hokkaido area were diagnosed as xeroderma pigmentosum (XP) at two University Hospital; one patient, a 29 years old female (XP2AS) at Asahikawa Medical College, and five patients, namely, a 53 years old male (XP1SA), a 45 years old female (XP2SA), a 46 years old female (XP3SA), a 47 years old male (XP4SA) and a 34 years old male (XP5SA) at Hokkaido University School of Medicine. All these XP patients showed mild skin symptoms and had no apparent neurological abnormalities. To identify genetic complementation groups of these patients, DNA repair capacities in skin fibroblasts derived from the patients were analyzed by ultraviolet light (UV)-induced unscheduled DNA synthesis (UDS), and also by colony-forming abilities of UV-irradiated cells incubated with or without caffeine added in post-UV culture medium. The levels of UDS measured by autoradiography in these XP cells irradiated with 20 J/m2 of UV were 67 to 84% of those of normal human fibroblasts. Although one XP cell strain (XP2AS) showed about 2-fold greater sensitivity to killing by UV than normal cells, UV sensitivities of the rest of 5 XP strains were similar or only slightly higher than those of normal cells. However, UV sensitivities of all the 6 XP cell strains markedly increased by addition of 1 mM caffeine in the post-UV incubation medium, a phenomenon characteristic of XP variant cells. We also analyzed post-replication repair in XP1SA cells by sedimentation of newly-synthesized DNA in alkaline sucrose gradient, and found that this strain is defective in this repair system. From these results, we concluded that all the 6 XP strains studied here belong to XP variants.
A study was conducted to examine the effect of endotoxin present in periodontal pockets on the proliferation and attachment of human cell lines on the culture plates (Ca9-22 and gingival fibroblasts). The endotoxin was collected from periodontal pockets of anterior teeth in patients with periodontal disease by subgingival irrigation with sterilized distilled water. The solutions obtained were then subjected to hot phenol-water extraction. The collected endotoxin from periodontal pocket and four other kinds of endotoxin obtained commercially as positive controls were added to cell cultures and the numbers of viable cells on the culture plates were counted. Among the commercially available endotoxins used in this study, only 500 micrograms/ml of endotoxin derived from Escherichia coli 0111:B4 significantly decreased the number of attachment cells of Ca9-22 and gingival fibroblasts on the culture plates. Endotoxin from periodontal pockets at 5 micrograms/ml also significantly decreased the numbers of attachment cells of both cell lines.
A study was conducted to investigate subgingival plaque formation on two types of dental implant material in the human oral cavity. Fifteen teeth affected by severe periodontitis and scheduled for extraction in five patients were selected. After thorough root planing, inlay cavities were prepared from the gingival margin to 5 mm subgingivally. Then, rectangular test specimens (polycrystal aluminum ceramic (P), single-crystal aluminum ceramic (S)) or a control dentin specimen (D) were installed in gold inlays, which were placed in the inlay cavities and left for 3, 7 or 21 d. As a consequence, 4 mm of the surface of each specimen was exposed to the environment of the periodontal pocket. After each test period, the specimens were removed from the inlays and examined by scanning electron microscopy (SEM). The results suggested that S is a more suitable dental implant material than P from the viewpoint of clinical application because of its lower degree of plaque accumulation.
The new cognition-enhancing agent nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384, CAS 77191-36-7) was assessed for dependence liability in rats using the DAF (drug admixed food) method and an intravenous self-administration system. In the physical dependence test, nefiracetam and codeine phosphate were administered to rats mixed with food for 43 days in a gradually increasing dosage schedule, followed by feeding a drug-free normal diet to detect signs of withdrawal. After the withdrawal, rats in the nefiracetam treated groups showed no withdrawal symptoms (e.g. body weight loss) and exhibited greater body weight gains than control. On the other hand, rats in the codeine phosphate treated group showed overt withdrawal symptoms (e. g. soft stool, diarrhea, vocalization) and a significant body weight loss, suggesting development of physical dependence on the drug. It was concluded that nefiracetam did not possess physical dependence liability in rats. In the reinforcement liability test, through an indwelling cannula implanted into the right jugular vein rats were allowed to self-administer nefiracetam, morphine hydrochloride or pentobarbital for 14 days. Saline was administered to negative control animals for the same period. The daily frequency of self-administration increased progressively with time in rats of the morphine hydrochloride and pentobarbital groups. In the nefiracetam groups, it remained comparable to or was even lower than that in the saline control group. When compared with the saline control, the group mean frequency of self-administration showed a tendency to be small for nefiracetam, whereas the morphine hydrochloride and pentobarbital showed greater frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)