Chronic mastoid sinusitis mimicking metastatic disease demonstrated by Tc-99m HMDP bone scintigraphy.
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Biomedical subjects
Publications and source records attributed to Y Ohmori.
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The distribution in the chicken of motoneurons innervating the hyolingual muscles, i.e. the M. branchiomandibularis (BM), M. ceratoglossus (CG), M. interceratobranchialis (CB), M. serpihyoideus (PH), M. stylohyoideus (YH) and one of the mandibular muscles, M. depressor mandibulae (DM), was examined by retrograde transport of horseradish peroxidase conjugated with wheatgerm agglutinin. Labelled motoneurons are found in the three subnuclei of the facial (VII) nucleus, as well as hypoglossal (XII) nucleus. The distribution of motoneurons projecting to the DM are observed in the three subnuclei, those of the BM, PH and YH in the intermediate and ventral subnuclei and those of the CB and CG in the intermediate subnucleus. Motoneurons projecting to the PH, YH, CB and CG are also distributed in the XII nucleus. The ratio of labelled motoneurons of the VII to XII nuclei decreases the PH, YH, CB and CG in that order, and the ratio of labelled ones of the ventral to intermediate subnuclei decreases the BM, PH and YH in that order. The topographical and functional aspects of the subdivision of the motor nucleus are discussed.
BACKGROUND: Since carcinoma of the esophagus is usually diagnosed at an advanced stage, many cases of esophageal cancer are beyond possible radical resection and only palliative treatment can be performed in such cases. Therefore, a great deal of discussion has taken place concerning indications for treatment modality, and various procedures have been performed to palliate such patients. The prognosis for such patients is still poor, even though many kinds of palliation have already been developed and applied. To improve the prognosis of such patients we developed a multidisciplinary treatment which includes high dose rate intraluminal brachytherapy (HDR-ILBRT) and evaluated its effectiveness, especially the HDR-ILBRT component. PATIENTS AND TREATMENT METHODS: Sixty-six patients with unresectable esophageal cancer enrolled in this study. Twenty-seven patients underwent bypass operations. Seven of the 27 patients received external irradiation only (group BE), 11 received external irradiation and HDR-ILBRT (group BEH), while the remaining 9 did not receive radiotherapy (group B). Another 39 patients without bypass operations were all treated with radiotherapy, 22 with external irradiation only (group E) and 17 were treated with external irradiation and HDR-ILBRT (group EH). After completion of radiotherapy, all patients received chemotherapy with 5-FU (2,500 mg/body) and CDDP (100 mg/body). RESULTS: Mean survival time and the 5-year survival rate of group BEH (13.3 +/- 1.5 months and 20%) were significantly improved compared with group BE + B (p < 0.05). In the patients without bypass operations, there were significant differences in the mean survival time and the 3-year survival rate in groups EH and E (group EH 16.5 +/- 2.5 months, 21.8%, group E 9.0 +/- 1.3 months, 0%, p < 0.05). The bypass operation itself and chemotherapy did not significantly affect the prognosis of patients with unresectable esophageal cancer. CONCLUSION: These results strongly suggest the use of HDR-ILBRT, as a component of multidisciplinary treatment for unresectable esophageal cancer, was significantly effective and HDR-ILBRT contributed to improve outcomes in patients with advanced esophageal cancer. HDR-ILBRT should be established as a component of treatments for unresectable esophageal cancer.
UNLABELLED: We synthesized fluorine-18-labeled fluoroboronophenylalanine (18F-10B-FBPA), an analog of boronophenylalanine (10B-BPA), and characterized its pharmacokinetics in patients with glioma. We conducted PET studies on three types of gliomas to clarify the relationship between tumor grade and each rate constant [K1 (ml/g/min), k2 (min[-1]) and k3 (min[-1])], and here, we discuss the metabolism of the 10B-BPA analog (18F-10B-FBPA). METHODS: Thirty-three cases of primary gliomas were studied by dynamic PET using DL-18F-10B-FBPA or L-18F-10B-FBPA. Dynamic PET images of 18F-10B-FBPA incorporation into tumors were obtained, and the arterial blood samplings were performed in all cases. RESULTS: When the dynamic PET data were represented as Gjedde-Patlak plots, there was a positive slope, suggesting the involvement of the putative metabolic pool of this tracer. A three-compartment model using rate constants (K1, k2 and k3) was used for the kinetic analysis. The accumulation of 18F-10B-FBPA was found to correlate with the degree of malignancy, and the L form of 18F-10B-FBPA was taken up better than was the DL form. The results of dynamic PET analysis suggested that K1 (measuring amino acid transport process) is a major factor determining the accumulation of 18F-10B-FBPA. A comparison of the rate constants revealed that k3 (metabolic process) did not correlate with the degree of malignancy. The absence of evident differences in k3 between DL and L forms suggests that k3 represents phenomena that are not dependent on the native form of L. CONCLUSION: These PET data will be of practical use for diagnosis of malignancy and direct prediction of the effectiveness of boron neutron capture therapy using 10B-BPA.
A 64-year-old female who was diagnosed with an amylase-producing tumor of unknown origin was treated by hyperthermochemotherapy. The patient was admitted with a complaint of abdominal fullness due to ascites. Laboratory examination showed high levels of serum amylase and tumor markers, including CA15-3, CA 125 and CA 72-4. Laparotomy showed peritoneal dissemination with histological findings of adenocarcinoma of unknown origin. After laparotomy, she was given hyperthermia combined with chemotherapy using carboplatin (CBDCA), mitomycin C (MMC) and doxifluridine (5'-DFUR). Hyperthermia (13.56 MHz radiofrequency for 40-50 min) was performed a total of six times within one and a half months. The total doses of CBDCA and MMC were 450 mg and 24 mg, respectively, and 600 mg of 5'-DFUR was orally administered every day. By these combined treatments, ascites disappeared and serum levels of amylase and all tumor markers were decreased and normalized. MRI and echo examination also showed complete disappearance of peritoneal metastasis. Two and a half years after the treatment, the patient is alive without any evidence of recurrence, which suggests that this combined therapy is one of the useful modalities for peritoneal dissemination as well as an inoperable tumor itself.
Determination of tumor boron-10 (10B) levels is required for accurate neutron dosimetry during boron neutron capture therapy. We assessed a new method for quantitative measurement of boronated drug uptake in high-grade gliomas. This method uses positron emission tomography (PET) with fluorine-18-labeled L-fluoroborono-phenylalanine (L-18F-10B-FBPA), which was synthesized as an analogue of L-boronophenylalanine. We studied the accumulation of L-18F-10B-FBPA by PET in patients with high-grade gliomas. Dynamic PET studies of brain tumors revealed that L-18F-10B-FBPA accumulated gradually after bolus injection, and the value of PET activity divided by the integrated plasma activity reached a constant level 42 min after injection, which was defined as the incorporation constant (Ic*). This constant reflected the appropriate L-18F-10B-FBPA accumulation in tumor tissue. Based on the Ic* constant, the methods for estimating tumor 10B concentration were devised. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This method was based solely on PET and can potentially provide data that would assist in the selection of patients for future treatment with boron neutron capture therapy after surgical resection of their brain tumors.
Based on pharmacokinetic findings of fluorine-18-labeled L-fluoroboronophenylalanine by positron emission tomography (PET), methods for estimating tumor 10B concentration were devised. In clinical practice of boron neutron capture therapy (BNCT) for high-grade gliomas, a large amount of L-boronophenylalanine (L-10B-BPA)-fructose solution is used. Under these conditions, a slow i.v. infusion of L-10B-BPA-fructose solution should be performed for BNCT; therefore, the changes over time in 10B concentration in the target tissue were estimated by convoluting the actual time course of changes in plasma 10B concentration with a PET-based weight function including the proper rate constants [K1 (ml/g/min), k2 (min(-1)), k3 (min(-1)), and k4 (min(-1))]. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This demonstrated the similarity in pharmacokinetics between fluorine-18-labeled L-fluoroboronophenylalanine and L-10B-BPA. This method, using the appropriate rate constant, permits the determination of tumor 10B concentration and is widely suitable for clinical BNCT, because the averaged PET data are enough to use in future patients without individual PET study.
The morphology and distribution of leucine-enkephalin (LENK)- and substance P (SP)-containing axon terminals in the hypoglossal nucleus of the chicken was investigated immunocytochemically at the electron microscopic level. The major findings of the present study were as follows: 1) Both LENK- and SP-immunoreactive (IR) profiles including unmyelinated axons, varicosities and axon terminals were found throughout the hypoglossal nucleus. 2) LENK-IR profiles without synapses (preterminal axons and varicosities) were observed more frequently (66%) than LENK-IR synaptic profiles (34%). In contrast, SP-IR synaptic terminals were seen more often (68%) than SP-IR terminals without synapses (32%). 3) Both LENK- and SP-IR synaptic terminals ending on dendrites were more numerous (83% and 94%, respectively) than those making synapses on somata (17% and 6%, respectively). 4) The average diameter of SP-IR synaptic terminals were significantly larger than that of LENK-IR ones. 5) Both LENK- and SP-IR synaptic terminals contained numerous small clear vesicles and several large dense-cored vesicles (LDV). Although both LENK- and SP-IR synaptic terminals contained LDV consistently, SP-IR synaptic terminals contained significantly more LDV than LENK-IR types. 6) Postsynaptic dense bodies (Taxi bodies) were seen more frequently in SP-IR synaptic terminals than in LENK-IR ones. These findings confirm both LENK and SP innervation in the hypoglossal nucleus and suggest a functional role as neuromodulator for the two neuropeptides in tongue control.
IL-4 suppresses the IFN-gamma-induced expression of the IFN regulatory factor-1 (IRF-1) gene, and this suppression is attenuated by increasing the amount of IFN-gamma. The effects of IFN-gamma and IL-4 on transcription of a reporter gene under control of a 1.3-kb fragment from the IRF-1 gene promoter or the STAT binding element (SBE) from this gene in the context of a heterologous promoter are similar to their effects on the endogenous IRF-1 gene. IFN-gamma-dependent transcription of reporter gene is suppressed by IL-4, but IL-4 alone has no trans-activating function. IL-4 treatment does not inhibit the tyrosine phosphorylation or nuclear translocation of IFN-gamma-activated STAT1. Rather, IFN-gamma and IL-4 independently activate STAT1 and STAT6, respectively, and both proteins bind to the IRF-1 SBE in homodimeric form. The affinity of STAT1 for the IRF-1 SBE is higher than the affinity of STAT6, as measured by competition with unlabeled oligonucleotide. These observations suggest that IL-4 may suppress IFN-gamma-stimulated transcription of the IRF-1 gene by activation of STAT6, which can compete with STAT1 for occupancy of the IRF-1 SBE when STAT1 levels are low. Suppression may be attenuated as the quantity of STAT1 relative to that of STAT6 increases in cells treated with increasing amounts of IFN-gamma and displaces STAT6.
LPS induces the expression of the gene encoding the type II TNF-alpha receptor in mononuclear phagocytes. To elucidate the nuclear signaling mechanisms involved in this response, a 772-bp fragment of the TNFRII gene promoter was analyzed by deletion and site-specific mutagenesis following transient transfection in the macrophage-like cell line RAW264.7. A region located between -100 and -75 relative to the transcription start site was found to be essential for LPS sensitivity. This contained a GC-rich region composed of two tandemly arrayed Sp-1 sites. While mutation of this region confirmed that it was essential for LPS sensitivity, the sequence was not able to confer LPS sensitivity upon a heterologous promoter. Internal deletion and site-specific mutagenesis of the 100-bp fragment identified regions immediately flanking an initiator region (Inr) site that were also necessary for sensitivity to LPS. Electrophoretic mobility shift assays demonstrated that the GC box bound Sp-1 and Sp-3, although the level of binding activity did not vary with LPS stimulation. An oligonucleotide probe containing nucleotide positions -45 to -18 also bound several protein complexes, but these were not enhanced by LPS. These findings indicate that the tandem GC box is necessary, but not sufficient, for LPS-mediated transcription of the TNFRII gene. A second apparently novel motif, located within 15 nucleotides of the Inr, is also necessary.
Interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha) cooperate to induce the expression of many gene products during inflammation. The present report demonstrates that a portion of this cooperativity is mediated by synergism between two distinct transcription factors: signal transducer and activator of transcription 1 (STAT1) and nuclear factor kappaB (NF-kappaB). IFNgamma and TNFalpha synergistically induce expression of mRNAs encoding interferon regulatory factor-1 (IRF-1), intercellular adhesion molecule-1, Mig (monokine induced by gamma-interferon), and RANTES (regulated on activation normal T cell expressed and secreted) in normal but not STAT1-deficient mouse fibroblasts, indicating a requirement for STAT1. Transient transfection assays in fibroblasts using site-directed mutants of a 1.3-kilobase pair sequence of the IRF-1 gene promoter revealed that the synergy was dependent upon two sequence elements; a STAT binding element and a kappaB motif. Artificial constructs containing a single copy of both a STAT binding element and a kappaB motif linked to the herpes virus thymidine kinase promoter were able to mediate synergistic response to IFNgamma and TNFalpha; such response varied with both the relative spacing and the specific sequence of the regions between these two sites. Cooperatively responsive sequence constructs bound both STAT1alpha and NF-kappaB in nuclear extracts prepared from IFNgamma- and/or TNFalpha-stimulated fibroblasts, although binding of individual factors was not cooperative. Thus, the frequently observed synergy between IFNgamma and TNFalpha in promoting inflammatory response depends in part upon cooperation between STAT1alpha and NF-kappaB, which is most likely mediated by their independent interaction with one or more components of the basal transcription complex.
In order to attain foreign gene expression in vivo in the testis of living mice, chloramphenicol acetyltransferase (CAT), firefly luciferase and bacterial lacZ reporter genes were transfected by microparticle bombardment and electroporation. The results showed that CAT reporter gene was expressed in a dose-dependent fashion. The X-gal staining showed that in some spermatogenic-like cells, the bacterial lacZ gene was also expressed by in vivo electroporation, but not by in vivo microparticle bombardment. The possibility of in vivo gene transfer to the spermatogenic cells of the mouse testis was further confirmed by the fact that the CAT reporter gene expression was testis-specific when driven by the mouse-protamin 1 promoter. It was concluded, therefore, that in vivo microparticle bombardment and, especially, electroporation provide convenient and efficient means of gene transfer to the testis of living mice.
By using three nonviral transfection methods, i.e., microparticle bombardment, lipofection and electroporation, the transfection efficiency and the expression intensity of a lacZ reporter gene were compared in developing chicken embryos in ovo. Of the three transfection methods employed, electroporation conferred the strongest expression of the bacterial lacZ gene with similar transfection efficiency. The results suggest that as far as transient gene expression is concerned, electroporation would provide a useful and efficient nonviral means of foreign gene transfection to somatic cells of living chicken embryos in ovo.
The identification of adrenaline- (A) and noradrenaline- (NA) containing cells in the adrenal medulla of the chicken and colocalization of serotonin and neuropeptides with A or NA in medullary cells were investigated with the use of immunohistochemical methods. Antisera against tyrosine hydroxylase and phenylethanolamine-N-methyltransferase were used as markers for catecholamine- and A-synthesizing cells, respectively. About 70% of catecholamine-synthesizing cells also exhibited immunoreactivity for phenylethanolamine-N-methyltransferase antiserum. Therefore, these cells are A-containing ones and the rest of cells seem to be NA-containing cells. Immunoreactivity with serotonin antiserum was observed in almost all medullary cells. Galanin-immunoreactivity was also found throughout the adrenal medulla, but was stronger in A-containing cells than in NA-containing ones. Cholecystokinin-immunoreactivity was restricted to A-containing cells. Methionine-enkephalin-immunoreactivity was seen in both A- and NA-containing cells, but in about half of medullary cells. From these results, it is suggested that serotonin, galanin, cholecystokinin, and methionine-enkephalin may be co-released with A and/or NA from adrenal medullary cells of the chicken.
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During infection with plerocercoids of Spirometra erinacei, organisms in the peritoneal cavity of infected animals have many bound inflammatory leukocytes yet survive apparently unharmed. Coculture of IFN gamma and LPS stimulated mouse peritoneal macrophages with live plerocercoids suppressed the mRNA expression of the inducible isoform of nitric oxide synthase (iNOS) and JE, the murine homologue of monocyte chemotactic protein-1 (MCP-1). Excretory/secretory (ES) products from plerocercoids also suppressed the induced iNOS and JE mRNA and reduced nitrite production of macrophages in a dose dependent manner. The suppression of inducible mRNA levels in macrophages cultured for 24 h with ES products varied with the nature of the stimuli; IFN gamma/ LPS-induced iNOS mRNA levels were effected less than were iNOS mRNA levels induced by IFN gamma/IL-2 or IFN gamma/ TNF alpha. Similar findings were obtained when nitrite production was measured. Thus modulation of LPS and cytokine inducible mRNA levels appear to be the primary target of ES products. We speculate that a major physiological role for this inhibitory activity in ES products might be the down regulation of pro-inflammatory gene expression.
Distributions of the cardiac plexuses and cardiac ganglia were gross-anatomically and histologically studied in eight Beijing ducks. The cardiac plexuses consisted of two components, the cardiac nerve arising from the sympathetic trunk and the cranial and caudal cardiac nerves arising from the vagus. Branches of these nerves made the cardiac plexuses on the epicardium. The cardiac plexuses could be divided into the six plexuses, that is, the right and left coronary plexuses, pericardiac transverse sinus plexus, caudal cardiac plexus, and right and left superior cardiac plexuses. There were small ganglia in the caudal cardiac plexus and the right and left coronary plexuses. These ganglia containing multipolar neurons were found like a linking chain in a single nerve.
Long-term mortality and morbidity was evaluated in 267 patients with a minimum follow-up of 10 yr and the physical status, graft function and quality of life in 15 patients with a functioning graft surviving for over 20 yr were reviewed. Actual patient and graft survival rates were 80.2% and 51.1% at 10 yr (n = 267) and 56.4% and 32.7% at 20 yr (n = 55), respectively. Although the rate of graft failure due to rejection was 4 times higher than that of patient death within 10 yr, it decreased to the level of patient death in the second decade. Dominant causes of death in patients with graft surviving for over 10 yr were hepatic failure due to viral hepatitis and malignancies. In 15 patients with graft currently surviving beyond 20 yr, while all patients have excellent graft function, malignancy occurred in 5, viral hepatitis in 3, aseptic necrosis in 3, and diabetes mellitus in one patient. No patient has suffered cardiovascular complications. Despite a high rate of morbidity, they show a satisfying status of rehabilitation (full time working 11/ 15, 73.3%). In order to attain more improved QOL in patients with long-term surviving renal transplant, close follow-up aiming at diminution of complications is required throughout the period after transplantation.