Stroboscopic detection of nuclear resonance in an arbitrary scattering channel.

The theory of heterodyne/stroboscopic detection of nuclear resonance scattering is developed, starting from the total scattering matrix as a product of the matrix of the reference sample and the sample under study. This general approach holds for all dynamical scattering channels. In the forward channel, which has been discussed in detail in the literature, the electronic scattering manifests itself only in an energy-independent diminution of the scattered intensity. In all other channels, complex resonance line shapes of the heterodyne/stroboscopic spectra are encountered, as a result of the interference of electronic and nuclear scattering. The grazing-incidence case will be evaluated and described in detail. Experimental data of classical X-ray reflectivity and their stroboscopically detected resonant counterpart spectra on the [(nat)Fe/(57)Fe]10 isotope periodic multilayer and antiferromagnetic [(57)Fe/Cr]20 superlattice are fitted simultaneously.

POEMS syndrome with Guillan-Barre syndrome-like acute onset: a case report and review of neurological progression in 30 cases.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare cause of demyelinating neuropathy with monoclonal plasma cell proliferation, and POEMS neuropathy is usually chronically progressive. Herein, the authors report a 34-year-old woman with POEMS syndrome presenting as acute polyneuropathy. Within 2 weeks of disease onset, she became unable to walk with electrodiagnostic features of demyelination and was initially diagnosed as having Guillan-Barré syndrome. Other systemic features (oedema and skin changes) developed later, and an elevated serum level of vascular endothelial growth factor led to the diagnosis of POEMS syndrome. She received high-dose chemotherapy with autologous peripheral blood stem cell transplantation, resulting in good recovery. The authors also reviewed patterns and speed of progression of neuropathy in the 30 patients with POEMS syndrome; 22 (73%) of them were unable to walk independently with the median period of 9.5 months from POEMS onset (range 0.5-51 months). Whereas the speed of neuropathy progression varies considerably among patients, some POEMS patients can show acute or subacute polyneuropathy. The early diagnosis and treatment could result in rapid improvement as shown in the present patient.

Neuromuscular transmission is not impaired in axonal Guillain--Barré syndrome.

BACKGROUND: Previous studies have shown that anti-GQ1b antibodies induce massive neuromuscular blocking. If anti-GM1 and -GD1a antibodies have similar effects on the neuromuscular junction (NMJ) in human limb muscles, this may explain selective motor involvement in axonal Guillain--Barré syndrome (GBS). METHODS: Axonal-stimulating single-fibre electromyography was performed in the extensor digitorum communis muscle of 23 patients with GBS, including 13 with the axonal form whose sera had a high titre of serum IgG anti-GM1 or -GD1a antibodies. RESULTS: All patients with axonal or demyelinating GBS showed normal or near-normal jitter, and no blocking. CONCLUSION: In both axonal and demyelinating GBS, neuromuscular transmission is not impaired. Our results failed to support the hypothesis that anti-GM1 or -GD1a antibody affects the NMJ. In GBS, impulse transmission is presumably impaired in the motor nerve terminal axons proximal to the NMJ.

The mammalian enzyme which replaces B protein of E. coli quinolinate synthetase is D-aspartate oxidase.

In Escherichia coli quinolinic acid, a precursor of NAD+, is synthesized from L-aspartate and dihydroxyacetone phosphate by two enzymes, an FAD-containing 'B protein' and 'A protein'. An enzyme which can replace the B protein in the E. coli quinolinate synthetase system when D-aspartate replaces L-aspartate as a substrate has been purified 300-fold from bovine kidney. This enzyme is shown to be identical with the previously described D-aspartate oxidase (D-aspartate:oxygen oxidoreductase (deaminating), EC 1.4.3.1). The immediate reaction product of D-aspartate oxidase (iminoaspartate) is condensed with dihydroxyacetone phosphate to form quinolinate in a reaction catalyzed by E. coli quinolinate synthetase A protein. In the absence of A protein (or dihydroxyacetone phosphate) iminoaspartate is spontaneously hydrolyzed to form oxaloacetate with a half-life of about 2.5 min at 25 degrees C and pH 8.0.

The effect of pyrazines on the metabolism of tryptophan and nicotinamide adenine dinucleotide in the rat. Evidence of the formation of a potent inhibitor of aminocarboxy-muconate-semialdehyde decarboxylase from pyrazinamide.

The intraperitoneal or oral administration of pyrazinamide and pyrazinoic acid (pyrazine 2-carboxylic acid) resulted in a marked increase of the NAD content in rat liver. The injections of pyrazine and pyrazine 2,3-dicarboxylic acid exhibited no significant effect on the hepatic NAD content. The boiled extract obtained from liver and kidney of rat injected with either pyrazinamide or pyrazinoic acid exhibited a potent inhibitory effect on the aminocarboxymuconate-semialdehyde decarboxylase (EC 4.1.1.45) activity in either lier or kidney, although pyrazinamide or pyrazinoic acid per se did not inhibit the enzyme activity. The unknown inhibitor of aminocarboxymuconate-semialdehyde decarboxylase was dialysable and heat-stable, and mostly excreted in urine by 6 and 12 h after injected of pyrazinoic acid and pyrazinamide, respectively. Pyrazine 2,3-dicarboxylic acid, pyrazine, nicotinamide, nicotinic acid, tryptophan, anthranilic acid, 5-hydroxyanthranilic acid and quinolinic acid exhibited no significant effect on the aminocarboxymuconate-semialdehyde decarboxylase activity in liver and kidney at the concentration of 1 mM in the reaction mixture. The expired 14CO2 from L-[benzen ring-U-14C]tryptophan was markedly decreased by the pyrazinamide injection, while the urinary excretion of 14C-labeled metabolites from L-tryptophan, mainly quinolinic acid, was markedly increased. These results suggest that the glutarate pathway of L-tryptophan was strongly inhibited by the inhibitor produced after the administration of pyrazinoic acid and pyrazinamide. Pyrazinamide but not pyrazinoic acid also exhibited a significant inhibition of the nuclear enzyme poly(ADP-ribose) synthetase in rat liver.

C225 antiepidermal growth factor receptor antibody enhances tumor radiocurability.

PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) has been correlated with tumor resistance to radiation. Blockade of EGFR with C225 anti-EGFR antibody was previously shown to synergistically enhance radiation-induced tumor growth delay. The purpose of this study was to assess whether C225 can increase tumor cure by radiation. METHODS AND MATERIALS: Nude mice bearing 8-mm-diameter A431 tumor xenografts in the hind leg were treated with C225 antibody, graded single doses of local tumor irradiation, or both. C225 was given i.p. at a dose of 1 mg/mouse 6 h before irradiation or 6 h before and 3 plus 6 days after irradiation. Tumor cure was the treatment endpoint assessed by the TCD(50) assay 120 days after treatment. The onset of recurrences of tumors not cured was also determined. RESULTS: C225 antibody increased the antitumor effects of radiation by reducing TCD(50) values and delaying tumor recurrences. Tumor radiocurability was enhanced by a factor of 1.18 by a single dose and by a factor of 1.92 by three doses of C225. Likewise, the appearance of tumor recurrences was delayed by a factor of 1.37 by a single dose and by a factor of 2.13 by three doses of C225. CONCLUSION: The data presented here demonstrate that C225 can increase tumor radiocurability and delay the appearance of recurrences of tumors not cured by radiation treatment.

Early radiation effects in highly apoptotic murine lymphoma xenografts monitored by 31P magnetic resonance spectroscopy.

PURPOSE: Phosphorus-31 magnetic resonance spectra (31P-MRS) were obtained from highly apoptotic murine lymphoma xenografts before and up to 24 hr following graded doses of radiation ranging from 2 to 30 Gy. Radiation-induced apoptosis was also estimated up to 24 hr by scoring apoptotic cells in tumor tissue. METHODS AND MATERIALS: Highly apoptotic murine lymphoma cells, EL4, were subcutaneously transplanted into C57/BL mice. At 7 days after transplantation, radiation was given to the tumor with a single dose at 3, 10, and 30 Gy. The beta-ATP/Pi, PME/Pi, and beta-ATP/PME values were calculated from the peak area of each spectrum. Radiation-induced apoptosis was scored with counting apoptotic cells on hematoxylin and eosin stained specimens (% apoptosis). RESULTS: The values of % apoptosis 4, 8, and 24 hr after radiation were 21.8, 19.6, and 4.6% at 3 Gy, 35.1, 25.6, and 14.8% at 10 Gy, 38.4, 38.0, and 30.6% at 30 Gy, respectively (cf. 4.4% in control). There was no correlation between early change in beta-ATP/Pi and % apoptosis at 4 hr after radiation when most of the apoptosis occurred. An early decrease in PME/Pi was observed at 4 hr after radiation dose at 30 Gy. For each dose, the values of beta-ATP/Pi 24 hr after radiation were inversely related to radiation dose. CONCLUSION: The increase in beta-ATP/Pi observed by 31P-MRS was linked to the degree of histological recovery from radiation-induced apoptosis.

Expression of vascular endothelial growth factor in human umbilical vein endothelial cells stimulated with interleukin-1alpha--an autocrine regulation of angiogenesis and inflammatory reactions.

Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells. We studied the production of VEGF by human umbilical vein endothelial cells (HUVEC) and smooth muscle cells (SMC) in response to the stimulation with interleukin-1alpha (IL-1alpha). HUVEC expressed VEGF mRNA in response to IL-1alpha in dose- and time-dependent manners. In HUVEC VEGF protein was detected only in cell lysates whereas in SMC most of the VEGF protein was detected in the conditioned medium. Immunofluorescent staining also confirmed the cell-associated VEGF in HUVEC. IL-1alpha also induced the expression of mRNA for IL-1alpha itself in HUVEC. Cycloheximide treatment of HUVEC slightly inhibited the IL-1alpha-induced expression of VEGF mRNA, and IL-1alpha may mediate, at least in part, VEGF expression in response to IL-1alpha. The growth of HUVEC stimulated with IL-1alpha was inhibited by a neutralizing antibody against VEGF. We conclude that IL-1alpha and VEGF may play an important role in autocrine growth regulation of HUVEC.

Radiation therapy for stage III non-small cell lung cancer invading chest wall.

The treatment outcome and prognostic factors for Stage III non-small cell lung cancer (NSCLC) invading the chest wall and treated with definitive radiation therapy alone were investigated. From 1976 to 1990, 40 consecutive patients with Stage III NSCLC invading the chest wall underwent radiation therapy alone. There were 31 with Stage IIIA and nine with Stage IIIB. Squamous cell carcinoma was present in 30 patients (75%). All the patients underwent radiation therapy at a total dose of 60-80 Gy at 2 Gy per fraction. Local pain completely disappeared in 11/13 (85%) and decreased in the remainder after treatment. The 5-year survival rate was 8% for all patients, 10% for Stage IIIA and 0% for IIIB (P = 0.02), 11% for lesions invading the parietal pleura and 0% for those invading the ribs or spine (P = 0.2). Good performance status, Stage IIIA, metastases of lymph nodes less than N3 and small tumor size were better prognostic factors by univariate analysis. By multivariate analysis, performance status (P = 0.01) and Stage (P = 0.03) were the important prognostic factors. Five-year local progression-free survival rates were 51% for patients with lesions invading the parietal pleura and 0% for those invading the ribs or spine (P = 0.009). Good pain relief was achieved in patients with lesions invading the ribs or spine by radiation therapy. Tumors invading the parietal pleura were fairly well controlled by radiation therapy alone.

Limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer.

The outcome of limited field irradiation for medically inoperable patients with peripheral stage I non-small cell lung cancer (NSCLC) was analyzed to discuss the elective irradiation of regional lymph nodes. From 1976 through 1994, 36 patients with peripheral stage I NSCLC were treated with definitive radiation therapy (RT) alone at Gunma University hospital. The total dose ranged from 60 to 81 Gy with a 2 Gy-daily standard fractionation, although only one patient received 48 Gy. Ten patients received elective irradiation of the regional lymph nodes with a total dose of 40 Gy or more. The overall response rate was 97% with 31% complete responses. The overall survival rates at 3 and 5 years were 42 and 23%, and disease-specific survival rates were 56 and 39% at 3 and 5 years, respectively. In 26 patients without the elective regional irradiation, disease-specific survival rates at 3 and 5 years were 53 and 40%, respectively, whereas they were 64 and 39% in 10 patients with the regional nodal irradiation. The cumulative 5-year local progression rate was 28%, and the overall progression rate was 60% at 5 years. Four patients had a local recurrence as the only site of initial tumor progression. Combined local and regional progression was seen in two patients, and one patient had a local recurrence in combination with distant metastasis. Twelve patients had distant failure without evidence of local or regional progression. Only one patient without regional nodal irradiation developed an isolated regional failure. No patient had serious complications related to RT. High-dose limited field RT is justified for medically inoperable patients with peripheral stage I NSCLC. The regional nodal irradiation can be omitted in these pulmonary compromised patients because of the low regional relapse rate. Dose-escalation by a conformal RT with a small target volume can be expected to provide a better local control rate and better survival.

Ca2+/protein modulator-dependent and -independent cyclic GMP phosphodiesterase from hog heart.

Ca2+/protein modulator-dependent and -independent guanosine 3':5'-monophosphate (cGMP) phosphodiesterases were separated from hog heart. The protein modulator-free Ca2+/protein modulator-dependent enzyme was partially purified by repeated DEAE-cellulose column chromatography and heat treatment. The final preparation of this enzyme showed no significant basal activity under the standard assay conditions. Lineweaver-Burk plots of the Ca2+/protein modulator-dependent enzyme activity indicated the presence of only a single kinetic form of the enzyme with Km=2.0 X 10(-6) M for for cGMP, whereas the plots for the independent enzyme were anomalous, showing both high and low K m values for cGMP. The Ca2+/protein modulator-dependent enzyme proved relatively stable at 48 degrees C for 1 h, but the independent form lost its activity under the same conditions. Furthermore, 50% inhibition of the dependent enzyme activity, but only 10% inhibition of the independent enzyme activity, was observed with 0.1 mM adenosine 3':5'-monophosphate (cAMP) when 1 muM cGMP was employed as a substrate.

Induction of p53-dependent apoptosis in vivo by nedaplatin and ionizing radiation.

p53 protein expression, apoptosis and growth delay induced by nedaplatin, a novel platinum compound, were investigated in vivo, and compared with those induced by ionizing radiation. A human ependymoblastoma with wild-type p53 was transplanted subcutaneously to the thighs of nude mice. The incidences of p53 protein-positive cells and apoptosis in tumors increased following exposure to ionizing radiation. In tumors treated with nedaplatin, they also increased, but the incidences of p53 protein-positive cells and apoptosis induced by 32 mg/kg nedaplatin, 1/2 LD50, were lower than those induced by 1 Gy irradiation. However, growth-delay assay showed no significant difference between the efficacy of 32 mg/kg nedaplatin and that of 1 Gy irradiation. These results suggest that the main antineoplastic activity caused by nedaplatin may be mediated through different mechanisms than those of the p53-dependent early apoptosis.

Experimental study of the effects on apoptosis of docetaxel alone and in combination with irradiation.

The effects of docetaxel alone and in combination with irradiation were experimentally investigated in terms of induction of apoptosis. A human ependymoblastoma was transplanted into nude mice, and they were intravenously injected with docetaxel, followed or preceded by irradiation with a single dose of 2 Gy. Apoptosis was less common in the docetaxel-alone group than in the irradiation-alone group. When administration of docetaxel was followed by irradiation, apoptosis was equal to or less common than in the irradiation-alone group. Apoptosis was most common in the irradiation-followed-by-docetaxel group. The incidence of mitosis was lower in the irradiation-alone group and the irradiation-followed-by-docetaxel group than in the docetaxel-alone group and the docetaxel-followed-by-irradiation group. The combined effect of irradiation and docetaxel appears to be useful in inducing apoptosis, but the sequence of irradiation and docetaxel is important.

Effect of paclitaxel pretreatment on radiation-induced p53-dependent apoptosis.

The aim of this study was to investigate the effect of paclitaxel on radiation-induced p53-dependent apoptosis. A human ependymoblastoma transplanted to nude mice was used. They were treated with paclitaxel (40 mg/kg), irradiation (2 Gy), or a combination of both. Apoptosis was markedly increased in the irradiation group. p53 protein expression was well correlated with the frequency of radiation-induced apoptosis. There was only a slight increase in apoptosis in the paclitaxel group, with little p53 protein expression. In the combination group, the frequency of apoptosis varied with the time intervals, and the group irradiated 12 h after paclitaxel administration showed much less apoptosis than the irradiation group. The Ki-67 labeling index in the paclitaxel group was always higher than before administration. The present study indicates that p53-dependent apoptosis was frequently induced in the human tumor in vivo by irradiation, but not by paclitaxel alone. When combined with irradiation, the timing affected the frequency of apoptosis and the degree of p53 protein expression.

Radiotherapy with concurrent docetaxel and carboplatin for head and neck cancer.

BACKGROUND: This study was designed to evaluate the concomitant use of docetaxel and carboplatin for radiosensitization in head and neck cancer. MATERIALS AND METHODS: One dose of docetaxel at 10 mg/m2 and five doses of carboplatin at AUC of 0.4 per week were administered to patients during the first two weeks of radiotherapy. Sixteen patients were treated with this regimen. Radiotherapy was given to a total dose of 64.8 to 82.0 Gy. Altered fractionation radiotherapy was performed in 12 patients with untreated advanced tumors. RESULTS: The complete response (CR) rate was 81%, with a partial response (PR) rate of 19%. Toxicities included grade 3 mucositis in 69% of patients and grade 2 dermatitis in 56% of patients. CONCLUSION: This schedule of docetaxel and carboplatin combined with radiotherapy may become a useful approach for the management of head and neck cancer with proper management of mucositis.

Clinical FDG-PET in diagnosis and evaluation of radiation response of patients with nasopharyngeal tumor.

BACKGROUND: We investigated the utility of clinical FDG-PET in patients with nasopharyngeal tumor treated by radiotherapy, retrospectively. MATERIALS AND METHODS: Fifteen patients with known or suspected nasopharyngeal tumors underwent FDG-PET. PET images were evaluated with visual interpretation qualitatively. Semiquantitative analysis was also performed on the metabolic ratios (MRs). RESULTS: The sensitivity and specificity of FDG-PET based on visual inspection were 92.9% (13/14) and 83.3% (10/12), respectively. There was a statistically significant difference between histological types in the mean MR. MR was significantly decreased by radiotherapy in patients with poorly differentiated squamous cell carcinoma. PET scans obtained 1-3 months after radiotherapy indicated decreased levels of FDG uptake in all tumors but one scan did not accurately reflect the status of the disease. CONCLUSION: These results are encouraging as to the clinical usefulness of FDG-PET for evaluating radiation effects in patients with nasopharyngeal tumor.

Cytotoxic effect of paclitaxel (taxol) either alone or in combination with irradiation in two rat yolk sac tumour cell lines with different radiosensitivities in vitro.

PURPOSE: To investigate the differences between two rat yolk sac tumour cell lines with different radiosensitivities in paclitaxel sensitivity and in the sensitizing effects of paclitaxel in combination with irradiation. MATERIALS AND METHODS: NMT-1 is a parent radiosensitive cell line and NMT-1R is a variant radioresistant cell line. RESULTS: Clonogenic assay demonstrated almost the same paclitaxel sensitivity with Do of 5.15 nM in NMT-1 and 5.02 nM in NMT-1R. Many apoptotic cells and DNA ladder formations were observed at 24 h after exposure to paclitaxel in both cell lines. The incidence of DNA fragmentation after 24 h exposure to 20 nM paclitaxel was 12.4 +/- 3.3% for NMT-1, and 13.0 +/- 1.9% for NMT-1R. Paclitaxel showed a supra-additive effect in combination with irradiation in both cell lines at 12 h after paclitaxel treatment only when the accumulation of cells in the G2/M phase reached its peak. CONCLUSIONS: Paclitaxel had the same cytotoxic effect in two cell lines with different radiosensitivity due to the induction of apoptosis. A supra-additive effect to radiation was observed with 12 h pretreatment in both cell lines. Paclitaxel may be effective for tumours with a component of different radiosensitivity in combination with irradiation.

Mechanism of chloramphenicol resistance in Bacillus badius 211.

Six strains of chloramphenicol (CM)-resistant endospore-forming bacteria, which can grow in the presence of 100 microgram/ml of CM, were isolated and identified as Bacillus badius. Mechanism of CM-resistance in one of the isolated strains, Bacillus badius 211, was investigated. No inactivation of CM was demonstrated when the strain was grown in nutrient broth containing 100 microgram/ml of CM, as evidenced by paper-disc bioassay of CM in the growth medium. In accordance with this result, no CM acetylation activity was demonstrated either with the intact cells or with the crude extracts of the CM-resistant strain. Poly U- and Poly A-directed polyphenylalanine and polylysine syntheses by S--30 preparations of both CM-resistant and CM-sensitive strains of Bacillus badius were almost equally inhibited by CM. From these results, the mechanism of CM resistance in Bacillus badius 211 seems to be due to other unknown mechanism.

Whole body PET for the evaluation of bony metastases in patients with breast cancer: comparison with 99Tcm-MDP bone scintigraphy.

The purpose of this study was to determine the potential role of positron emission tomography (PET) using 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) for the evaluation of bony metastasis compared with 99Tcm-methylene diphosphonate (99Tcm-MDP) bone scintigraphy in patients with breast cancer. Fifty-one female patients with breast cancer who had PET together with a bone scan within 1 month between September 1994 and March 1997 were included in this study. The median age was 49 years (range 29-79 years). The sensitivity, specificity and accuracy of the bone scan were 77.7%, 80.9% and 80.3%, respectively. On the other hand, for the detection of bone metastases PET had a sensitivity, specificity and accuracy of 77.7%, 97.6% and 94.1%, respectively. In the diagnosis of bony metastasis derived from breast cancer, FDG-PET was statistically superior to bone scintigraphy in its specificity. In conclusion, FDG-PET appears to be a powerful tool not only in the diagnosis of the primary lesion and soft tissue metastasis, but also in the diagnosis of bony metastasis among patients with breast cancer.

Development of a health guidance support system for lifestyle improvement. Committee of Health Evaluation Support System Council of Japan AMHTS Institutions.

OBJECTIVE: To provide automated advice for lifestyle adjustment based on an assessment of the results of a questionnaire and medical examination or health checkup data. METHODS: A system was developed that gathers data based on questions regarding weight gain, exercise, smoking, sleep, eating habits, salt intake, animal fat intake, snacks, alcohol, and oral hygiene; body mass index, resting blood pressure, fasting blood sugar, total cholesterol, triglycerides, uric acid and liver function tests. Based on the relationships between the lifestyle data and the health checkup data, a health assessment sheet was generated for persons being allocated to a multiple-risk-factor syndrome group. RESULTS: Health assessment and useful advice for lifestyle improvement were automatically extracted with the system, toward the high risk group for lifestyle related diseases. The system is operational. CONCLUSIONS: We developed a health guidance support system for lifestyle improvement. In comparison with conventional, limited advice methods, we developed a practical system that defined the necessity for lifestyle improvement more clearly, and made giving advice easier.