Pulse Energy and Pulse Duration Effects in the Ionization and Fragmentation of Iodomethane by Ultraintense Hard X Rays.

The interaction of intense femtosecond x-ray pulses with molecules sensitively depends on the interplay between multiple photoabsorptions, Auger decay, charge rearrangement, and nuclear motion. Here, we report on a combined experimental and theoretical study of the ionization and fragmentation of iodomethane (CH_{3}I) by ultraintense (∼10^{19} W/cm^{2}) x-ray pulses at 8.3 keV, demonstrating how these dynamics depend on the x-ray pulse energy and duration. We show that the timing of multiple ionization steps leading to a particular reaction product and, thus, the product's final kinetic energy, is determined by the pulse duration rather than the pulse energy or intensity. While the overall degree of ionization is mainly defined by the pulse energy, our measurement reveals that the yield of the fragments with the highest charge states is enhanced for short pulse durations, in contrast to earlier observations for atoms and small molecules in the soft x-ray domain. We attribute this effect to a decreased charge transfer efficiency at larger internuclear separations, which are reached during longer pulses.

Femtosecond response of polyatomic molecules to ultra-intense hard X-rays.

X-ray free-electron lasers enable the investigation of the structure and dynamics of diverse systems, including atoms, molecules, nanocrystals and single bioparticles, under extreme conditions. Many imaging applications that target biological systems and complex materials use hard X-ray pulses with extremely high peak intensities (exceeding 1020 watts per square centimetre). However, fundamental investigations have focused mainly on the individual response of atoms and small molecules using soft X-rays with much lower intensities. Studies with intense X-ray pulses have shown that irradiated atoms reach a very high degree of ionization, owing to multiphoton absorption, which in a heteronuclear molecular system occurs predominantly locally on a heavy atom (provided that the absorption cross-section of the heavy atom is considerably larger than those of its neighbours) and is followed by efficient redistribution of the induced charge. In serial femtosecond crystallography of biological objects-an application of X-ray free-electron lasers that greatly enhances our ability to determine protein structure-the ionization of heavy atoms increases the local radiation damage that is seen in the diffraction patterns of these objects and has been suggested as a way of phasing the diffraction data. On the basis of experiments using either soft or less-intense hard X-rays, it is thought that the induced charge and associated radiation damage of atoms in polyatomic molecules can be inferred from the charge that is induced in an isolated atom under otherwise comparable irradiation conditions. Here we show that the femtosecond response of small polyatomic molecules that contain one heavy atom to ultra-intense (with intensities approaching 1020 watts per square centimetre), hard (with photon energies of 8.3 kiloelectronvolts) X-ray pulses is qualitatively different: our experimental and modelling results establish that, under these conditions, the ionization of a molecule is considerably enhanced compared to that of an individual heavy atom with the same absorption cross-section. This enhancement is driven by ultrafast charge transfer within the molecule, which refills the core holes that are created in the heavy atom, providing further targets for inner-shell ionization and resulting in the emission of more than 50 electrons during the X-ray pulse. Our results demonstrate that efficient modelling of X-ray-driven processes in complex systems at ultrahigh intensities is feasible.

Treatment with lactose (galactose)-restricted and medium-chain triglyceride-supplemented formula for neonatal intrahepatic cholestasis caused by citrin deficiency.

Citrin plays a role in the transfer of NADH-reducing equivalent from cytosol to mitochondria as part of the malate-aspartate shuttle in liver. Citrin deficiency may cause an impairment of glycolysis due to an increase in the cytosolic NADH/NAD ratio leading to an energy shortage in the liver. Mutations of the SLC25A13 gene are responsible for neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). Most patients with NICCD show a resolution of symptoms within the first year of life, but some patients present with severe symptoms and require liver transplantation. We treated four patients including three siblings with NICCD by lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula. This formula rapidly improved the clinical condition and laboratory findings. Early treatment was more effective and did not require long-term administration. Lactose (galactose)-restriction can avoid further increase in the cytosolic NADH/NAD ratio in the liver and MCT supplementation can provide energy to hepatic cells by producing an excess of acetyl-CoA in mitochondria. Early treatment with lactose (galactose)-restricted and MCT-supplemented formula is recommended for patients with NICCD and possibly for patients with CTLN2.

Tight regulation of transgene expression by tetracycline-dependent activator and repressor in brain.

Methods to temporally and spatially regulate gene mutations will provide a powerful strategy to investigate gene function in the brain. To develop these methods, we have established a tightly regulated system for transgene expression in the forebrain using both a tetracycline (Tc)-dependent transcription activator (rtTA) and a repressor (TetR-Kruppel-associated box). In this system, the repressor binds to the Tc-responsive element (TRE) in the absence of doxycycline (Dox), leading to the repression of leaky activation of TRE-mediated transcription caused by weak binding of rtTA to TRE. Upon Dox administration, only the activator binds to TRE and activates transcription. We tested this system in cultured cells by bicistronically expressing both the regulators using an internal ribosome entry site (IRES). In COS-1, HeLa and SHSY5Y cells, leaky transcription activation led by rtTA in the absence of Dox was repressed without decreasing the level of activated transcription in the presence of Dox. Using this system, transgenic mice were produced that express both the regulators using IRES in the forebrain under the control of the alphaCaMKII promoter and were bred with transgenic mice carrying the TRE-dependent reporter transgene. In reverse transcription-polymerase chain reaction and in situ hybridization analyses of the forebrain in adult double transgenic mice, the treatment of Dox induces reporter mRNA expression, which was not detected before the treatment and after the withdraw of Dox following the treatment. These results indicate that this system allows the tight regulation of transgene expression in a Dox-dependent fashion in the forebrain and will be useful in investigating gene function in the brain.

Preoperative airway evaluation using multi-slice three-dimensional computed tomography for a patient with severe tracheal stenosis.

A 71-yr-old female with a malignant thyroid tumour was to undergo thyroidectomy under general anaesthesia. Preoperative chest x-ray and plain computed tomography (CT) showed severe tracheal stenosis. Three-dimensional figures of the trachea and a virtual bronchoscopic movie were obtained from multi-slice CT to evaluate the stenotic region and to simulate fibroscopic tracheal intubation, respectively. After induction of general anaesthesia with propofol, a tracheal tube was successfully passed through the stenotic region under the guide of a fibroscope as simulated in the virtual movie. We conclude that multi-slice CT is useful for preoperative airway evaluation for patients with stenosis and distortion of the trachea.

The effect of pre-operative administration of midazolam on the development of intra-operative hypothermia.

(Midazolam is often used for premedication; it is known to promote vasodilation and may therefore affect redistribution of heat during surgery. We examined the effect of pre-operative administration of midazolam on the development of intra-operative hypothermia. Forty-five patients were randomly allocated to one of three groups to receive no premedication (Group C), IM midazolam 0.04 mg.kg(-1) (Group M1) or 0.08 mg.kg(-1) (Group M2) 30 min prior to anaesthesia. Sedation levels were assessed, and then general anaesthesia was induced and maintained using propofol and fentanyl. During surgery, core temperature, which was similar for the three groups prior to induction of anaesthesia, decreased significantly less in the midazolam groups M1 and M2 compared to the control group C. Patients who were more heavily sedated prior to induction of anaesthesia, had significantly lower core temperatures peri-operatively than those who were less sedated, and core temperatures in unpremedicated patients fell to significantly lower levels during surgery than those who were drowsy. We conclude that pre-operative administration of midazolam produces an effect on the development of peri-operative hypothermia. We found that moderate pre-operative sedation reduces the peri-operative heat loss, possibly by affecting core-to-peripheral heat distribution.

Recurrent neurological symptoms in a patient following repeat combined spinal and epidural anaesthesia.

A healthy woman developed neurological symptoms after two consecutive Caesarean sections under combined spinal and epidural anaesthesia. Amethocaine was used for spinal anaesthesia and mepivacaine for epidural anaesthesia on both occasions, and a combination of fentanyl and bupivacaine was continuously infused for pain relief after the second. Her symptoms on both occasions were similar, including pain in the buttocks of 7-11 days duration and numbness in the sacral area of 5-6 months.

IM droperidol as premedication attenuates intraoperative hypothermia.

PURPOSE: Perioperative hypothermia results largely from core-to-peripheral heat redistribution. Droperidol, which is often used for premedication, promotes vasodilation, and thus may affect redistribution of heat. Accordingly, we tested the hypothesis that preanesthetic droperidol would affect perioperative hypothermia. METHODS: Twenty-three ASA physical status I patients scheduled for arthroscopic ligament reconstruction were randomly assigned to two groups to receive no premedication or im droperidol 0.1 mg x kg(-1) 30 min before anesthesia. Anesthesia was induced and maintained with propofol and fentanyl. We monitored core (tympanic) and peripheral (palm) temperatures, and skin (fingertip) blood flow for two hours after the induction of anesthesia during surgery. RESULTS: Before the induction of anesthesia, patients given droperidol were more deeply sedated than those given no premedication. Core temperature, which was similar in both groups before induction, decreased significantly more in the control than in the droperidol patients (0.75 +/- 0.34 degrees C and 0.37 +/- 0.20 degrees C, respectively, at 75 min after induction; P <0.01). Preinduction peripheral temperature and skin blood flow were lower in the control group than in the droperidol group, but the two variables became similar in both groups after induction. CONCLUSION: The results of the present study confirm our hypothesis that premedication with droperidol affects perioperative hypothermia. Droperidol may prevent core-to-peripheral heat redistribution after the induction of anesthesia.

Spinal anesthesia with tetracaine in 7.5% or 0.75% glucose in adolescents and adults.

UNLABELLED: To examine whether adolescents and adults might develop different anesthetic distribution and hemodynamic consequences after spinal injection of 0.5% tetracaine in 7.5% or 0.75% glucose, we studied 100 ASA I or II patients who were scheduled for elective surgery to the lower limb and fulfilled the following criteria: age between 13 and 16 yr (Adolescent group, n = 40) or between 25 and 74 yr (Adult group, n = 60); height between 155 and 180 cm; and body mass index between 18 and 32 kg/m(2). Patients in each group were then randomly divided into two equal subgroups to receive spinal anesthesia with 0.5% tetracaine in either 7.5% or 0.75% glucose with 0.125% phenylephrine at the L3-4 interspace. With patients in the supine horizontal position, neural block was assessed by cold, pinprick, and touch sensation and a modified Bromage scale after the injection of the study drug. The 7.5% glucose solution produced a significantly higher and faster spread of blockade in adolescents than in adults. In contrast, there were no differences in the levels of three sensory modalities between the two age groups after the 0.75% glucose solution, which produced a lower spread of blockade than the 7.5% glucose solution in either age group. Adolescents given the 0.75% glucose solution developed a smaller maximum decrease in systolic pressure than those given the heavier solution. We conclude that adolescents may develop an extensive level of blockade more easily and quickly than adults after intrathecal hyperbaric tetracaine, but that the difference may be reduced by using a less heavy solution. IMPLICATIONS: The influence of age on the characteristics of spinal anesthesia is still controversial. Our results show that adolescents develop blockade more extensively and quickly than adults after spinal anesthesia with 0.5%tetracaine in 7.5% glucose but not after the 0.75% glucose solution.

Tracking of individual nanocrystals using diffracted x rays

We demonstrated dynamical observation of an individual nanocrystal in supercooled liquid water with the guidance of x-ray diffracted spots from the nanocrystal itself. This new system, which we call diffracted x-ray tracking, monitored small Brownian motions (D=0.68 mrad(2)/s at 233 K) of a single nanoparticle in real time and real space.

Structure-activity relationships of (1'S)-1'-acetoxychavicol acetate, a major constituent of a southeast Asian condiment plant Languas galanga, on the inhibition of tumor-promoter-induced Epstein-Barr virus activation.

The structure-activity relationships of (1'S)-1'-acetoxychavicol acetate (ACA), a cancer chemopreventive agent of food origin, were investigated in an inhibitory test of tumor promoter teleocidin B-4-induced Epstein-Barr virus (EBV) activation in Raji cells. Through a test of 16 derivatives, the structural factors regulating activity were found to be as follows: (1) the absolute configuration at the 1'-position does not affect activity; (2) hydrogenation of the terminal methylene group abolishes activity; (3) both the phenolic and alcoholic hydroxyl groups are compulsorily acetylated, and it is necessary that the former is oriented only at the position para to the side chain; (4) an additional acetoxyl group is allowed to locate at the ortho or meta position; and (5) substitution of the hydrogen atom at the 1'-position by a methyl group reduces activity. Upon esterase blockade in Raji cells, (1'R,S)-ACA suppressed EBV activation, the extent of which was the same as tested in the control, suggesting that ACA bearing two acetoxyl groups is an intracellular structure prerequisite for activity exhibition. The present study suggests that nucleophilic attack to the 3'-position is important and involved in the interaction of ACA with an unidentified target molecule(s) participating in the process of EBV activation.

[Epidural anesthesia and general anesthesia using the cuffed oropharyngeal airway for an obese patient with Duchenne's muscular dystrophy].

Duchenne's muscular dystrophy is a genetic disorder whose features include abnormal responses to muscular relaxants and possible respiratory dysfunction after general anesthesia. The purpose of this report is to describe one management strategy used successfully to anesthetize an obese man with this disorder for atypical mastectomy. The anesthetic management during surgery involves epidural anesthesia using 2% mepivacaine and general anesthesia using the cuffed oropharyngeal airway. Postoperatively 0.25% bupivacaine was infused for epidural analgesia. The patient was observed in the intensive care unit until the first postoperative day and showed an uncomplicated intra- and post-operative course.

Motility of the canine pyloric ring following a pylorus-preserving pancreatoduodenectomy.

Recently, function-preserving operations have become popular, and pylorus-preserving pancreatoduodenectomy (PPPD) is frequently performed for diseases of the head of the pancreas. However, there are only a few basic studies on the pyloric function after PPPD. Using strain gauge force transducers (SGTs), we studied the pyloric motility of normal and PPPD dogs. We prepared three normal and three PPPD dogs in which the SGTs were implanted onto the antrum and pyloric ring, etc. In conscious dogs, the spontaneous gastrointestinal motility was recorded, and the plasma motilin concentration was measured during the interdigestive state. Following the administration of exogenous Leu13-motilin, the motility was again recorded. The relaxation and opening of the pyloric ring was observed synchronously with intense contractions of the antrum during the phase III of normal dogs. Phase III-like motility was recorded in the PPPD dogs, which was not a typical periodic motility. The plasma motilin concentration of one PPPD dog could be measured, and the motilin levels during the phase III-like motility were higher than during phase I. The phase III-like motility was induced by Leu13-motilin in both normal and PPPD dogs. The phase III-like motility recorded in the PPPD dogs was not a typical periodic one, and this aberrant motility was considered to be one of the causes of delayed gastric emptying. Phase III-like motility was induced by the administration of Leu13-motilin; therefore, it is possible that Leu13-motilin improved the motility of the pyloric ring after PPPD.

Pyloric opening and closure evaluated by means of strain gauge force transducers.

Recently, gastrointestinal motility research and various studies to measure motility have been conducted. However, it is not easy to measure the pyloric sphincter motility, especially its open and closed motility. There are few reports on the opening and closed motility of the pyloric ring. In this study, I examined the pyloric motility with strain gauge force transducers (SGTs). SGTs were implanted onto the antrum, pyloric ring and duodenum of a dog. In order to clarify the relationship between the opening and closed motility of the pylorus and SGTs recordings, the pyloric ring was observed with a gastrofiberscope while measurements were taken using the SGTs in anesthetized dogs. In addition, the pyloric ring was extended mechanically with a balloon and measurement were taken using the SGTs. In conscious dogs, the natural gastropyloroduodenal motility was recorded. Then, cisapride, erythromycin, and Leu13-motilin were administered in the interdigestive state and the motility was recorded. The pyloric opening and closed motility could be monitored using SGTs. The pyloric ring opened when the pyloric motility recorded using the SGTs showed a negative deflection. In addition, in phase III, when intense contraction of the antrum was observed, relaxation and opening of the pyloric ring could be observed. Erythromycin and Leu13-motilin induced phase III-like motility and relaxation of the pyloric ring. However, in cisapride-induced motility, relaxation of the pyloric ring was not observed. The pyloric ring opening and closed motility can be monitored using SGTs and this method is effective for the evaluation of the pyloric function.

Studies of postoperative transarterial infusion chemotherapy for liver metastasis of colorectal carcinoma after hepatectomy.

BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy of postoperative transarterial infusion chemotherapy (PTIC) for the prevention of metastatic liver cancer recurrence after hepatectomy following curative surgery for colorectal carcinoma. METHODOLOGY: Thirty-eight patients who underwent curative hepatectomy for metastatic liver cancer from colorectal carcinoma were studied. Ten out of the 38 patients received PTIC (experimental group) and 28 patients did not receive chemotherapy (control group). PTIC was performed with an intrahepatic indwelling catheter, which was set-up for 3 weeks and repeated 3 times in two monthly intervals. RESULTS: In the control group, no significant differences were observed in the survival between patients with a single hepatic nodule and those with multiple hepatic nodules. Between patients with hepatic tumors of more than 3 cm in diameter and those with tumors less than 3 cm, and between patients with tumors located at H1 and H2, no significant differences were seen, either. However, the 5-year survival rate of the patients with metachronous liver metastases was 90% which was significantly better than for those patients with synchronous liver tumors (p < 0.05). The 100% of 3- and 100% of 4-year survival rates of the experimental group were significantly better than the 60% and 47% respectively of the control group (p < 0.05). The non-recurrence rate in the remnant liver was also significantly better in the experimental group than that in the control group (p < 0.01). The adverse effect of this protocol was negligible. CONCLUSION: We conclude that PTIC improved the survival and non-recurrence rate in the remnant liver of the patients with liver metastases from colorectal cancer after hepatectomy, and was considered to be safe and an important protective factor for the prevention of recurrence of liver metastases after hepatectomy.

Inflammatory fibroid polyp of the ileum with the appearance of a Borrmann type II lesion, caused by colostomy irrigation: report of a case.

Inflammatory fibroid polyps (IFPs) are rarely found in the gastrointestinal tract. The majority of IFPs are sessile-pedunculated or pedunculated polypoid lesions, whereas a polyp presenting like a Borrmann type II lesion is extremely unusual. This report describes the case of a 74-year-old man with a history of intussusception, in whom a preoperative diagnosis of a cecal tumor of the ileocecal valve was made. A laparotomy subsequently revealed a lesion similar to a Borrmann type II tumor located 15 cm above the ileocecal valve, but not at the valve. The lesion was diagnosed as an IFP which had been caused by repeated colostomy irrigation. The aim of the present report is to draw attention to this entity, which should be included in the differential diagnosis of intussusception and small bowel obstruction.

[Effective administration of recombinant granulocyte colony-stimulating factor to prevent granulocytopenia due to combination chemotherapy for testicular germ cell tumors].

A prospective randomized study on the administration of recombinant granulocyte colony stimulating factor (rG-CSF) was conducted on 15 patients with testicular germ cell tumors. The clinical stagings of all patients except one were minimal to moderate extent according to the Indiana University staging system. Combination chemotherapy using bleomycin, etoposide and cisplatinum (BEP) was performed as the initial treatment on the eligible patients. rG-CSF was administered by two different methods; 1) routine administration on the 6th day after BEP chemotherapy (group A), and 2) the same method, but after granulocytopenia of 1,500/mm3 had developed (group B). The administration of rG-CSF in group A significantly reduced the severity of leucocytopenia and also the incidence of stomatitis compared with group B. Although rG-CSF produced no significant side effects, the thrombocytopenia was prominent in the group A patients (not significant). BEP chemotherapy itself is an easily-tolerable and well established method for treating young adult patients. The method used in group B seems to be suitable in situations where thrombocytopenia and cost effectiveness.

[Tumor size and DNA ploidy changes in renal cell carcinomas--flow cytometric analysis of DNA content in renal cell carcinomas associated with von Hippel-Lindau disease].

BACKGROUND: Renal cell carcinomas (RCCs) develop in 8-63% of von Hippel-Lindau disease (VHL) patients, and loss of 3p segments, chromosome aberrations found in 90% of sporadic RCCs, has also been observed in RCCs associated with VHL. In fact, comparative analysis showed that the chromosome aberrations in RCCs associated with VHL are similar to those found in sporadic RCCs. VHL patients have the whole spectrum of tumors from small early lesions to large ones in the same kidney, providing a unique opportunity to analyze tumors in different stages of development. Subsequently deoxyribonucleic acid (DNA) content in RCCs of VHL patients was examined and correlated to their tumor size to gain some insight in the progression of sporadic RCCs. METHODS: From 1988 to 1991, we have experienced 6 cases of RCCs associated with VHL who underwent partial or radical nephrectomy. A total number of 52 paraffin-embedded samples from 33 RCCs from 6 patients with VHL was analyzed by flow cytometry. RESULTS: The sizes of tumors ranged from 0.2 to 8.2 cm. DNA aneuploid patterns demonstrated in none of 9 tumors less than 1.6 cm, 4 of 14 tumors (29%) as large as 1.6 to 2.5 cm, and 5 of 10 tumors (50%) larger than 2.5 cm (p < 0.05). Twelve tumors less than 1.8 cm showed DNA diploid, so the smallest size of aneuploid tumors was 1.8 cm. CONCLUSION: These data suggest that DNA ploidy change (diploid to aneuploid) in RCCs probably takes place as tumors grow approximately 1.8 cm in size.

[Studies on nuclear DNA content in bladder cancers using flow cytometry].

This study was designed to evaluate the clinical relevance between the DNA ploidy and histopathology, and the incidence of the DNA heterogeneity in patients with bladder cancers. Flow cytometry(FCM) was used to study the DNA ploidy in 63 patients who underwent total cystectomy. The DNA ploidy and DNA index were analyzed by FCM in total 478 paraffin embedded samples (7.6 samples per case on the average). The DNA ploidy of 52 bladder cancers, that had coexisted after total cystectomy, showed that 24 cases, 46% were DNA aneuploid and 18 cases, 35% had DNA heterogeneity. The other 11 cases which were found to be pT0 after cystectomy were all DNA diploid. There were significantly good correlation among DNA ploidy pattern and intravesical involvement (lymph-duct involvement and venous involvement), but were not among the DNA ploidy pattern and tumor grade and stage. With regard to the evaluation of two vertically devided samples of tumors, DNA aneuploid had been not always recognized in the deeper samples, therefore, the author did not determine that there was good correlation between the DNA ploidy and the tumor invasion. In lymph node metastases, the 39 diploid tumors had given rise to lymph node metastases in only 5 cases(13%), whereas 11 cases(46%) of the 24 aneuploid tumors had metastasized(p < 0.01). Eleven of 16 lymph node metastases were DNA diploid and the others were DNA aneuploid. These data suggest that although the incidence of DNA heterogeneity in bladder cancers (35%) is thought to be relatively small, the DNA ploidy will be able to be the important prognosticating factor in bladder cancers.