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Although most patients in the intensive care unit (ICU) receive antibiotics, little is known about patterns of antibiotic use in ICUs in Japan. The objective of this study was to evaluate the pattern of antibiotic use in ICUs. A nationwide one-day cross-sectional surveillance of antibiotic use in the ICU was conducted three times between January 2011 and December 2011. All patients aged at least16 years were included. Data from 52 ICUs and 1148 patients were reviewed. There were 1028 prescriptions for intravenous antibiotics. Of 1148 patients, 834 (73%) received at least one intravenous antibiotic, and 575 had at least one known site of infection. Respiratory and intra-abdominal infections were the two most common types. Of 1028 prescriptions, 331 (34%) were for surgical or medical prophylaxis. Excluding prophylaxis, carbapenems were the most commonly prescribed agent. Infectious disease consultations, pre- and post-prescription antimicrobial stewardship, and ICU-dedicated antibiograms were available in 44%, 52%, 77%, and 21% of the ICUs, respectively. In logistic regression analysis adjusting for patient characteristics, treatment in a university hospital (adjusted odds ratio, 1.72; 95% CI, 1.05–2.84; P = 0.033) and an open ICU (adjusted odds ratio, 2.30; 95% CI, 1.02–5.17; P = 0.044) were significantly associated with greater likelihood of carbapenem use. An increase in the number of closed ICUs and more intensive care specialists may reduce carbapenem use in Japanese ICUs. Large-scale epidemiological studies of antimicrobial resistance in the ICU are needed.

We have already proposed a triple-tuned voltage-controlled oscillator (VCO) for achieving an ultra-wideband characteristic. The triple-tuned VCO consists of an active device and three tuned circuits. The fabricated VCO has achieved the oscillation bandwidth of 5.6-16.8 GHz and the phase noise of -114.9 dBc/Hz +/-2.9 dB at 1-MHz offset from the carrier. In this paper, for the first time, the conditions that the VCO achieves the ultra-wideband characteristic are clarified by formulation and simulation. It is also clarified that a transistor of the larger emitter size is suitable for the wideband VCO. In addition, the performances of the proposed VCO are compared with other reported wideband VCOs. As a result, it is shown that the proposed VCO has achieved the lowest figure of merit in the C-Ku-band.

We sampled cultured juveniles of the ayu Plecoglossus altivelis that would be used for river stocking, to evaluate histologically the development of the organs that are important for immunological competence of the fish. These samples included hatchery-produced fish reared in three different facilities (sample A), fish captured in Lake Biwa when they were larvae and cultured by three different fish farmers (B), and wild juveniles as the control. Each sample consisted of at least 10 fish. Histological observation and following quantification showed clear positive correlation of the thymus volume and the body length of the wild fish. However, the fish in each 2 groups of the samples A and B had significantly smaller thymuses than those of the wild fish of corresponding body lengths. Congestive splenomegaly was often observed in the cultured fish for both groups. To know the rearing conditions that affect thymus development, a preliminary experiment was conducted in which larval ayu were reared in aquaria for 3 months in four different rearing conditions with the combinations of two different water temperatures (13.8 and 17.2 °C) and two different stocking densities (0.25 and 2.5 kg/m3 at the start of the experiment). The result showed that both the high water temperature and the high rearing density suppressed development of the thymus significantly, whereas the fish reared in the combination of low water temperature and low rearing density developed the thymuses of the comparable size to those of the wild fish. These results suggest that inappropriate culture conditions may suppress the thymus development, even if the fish appear to grow normally.

Nitric oxide (NO) activates corpus cavernosum smooth muscle soluble guanylate cyclase (sGC) and increases the synthesis of cGMP that results in smooth muscle relaxation and ultimately, penile erection. To characterize sGC and define the potential synergy between NO and the allosteric activator YC-1 in corpus cavernosum, rat sGC was activated by either sodium nitroprusside (SNP) or YC-1, and YC-1 potentiated the effects of SNP with a 200-fold activation of sGC. Both SNP and YC-1 decreased the Km and increased the Vmax. ODQ significantly inhibited sGC activated by SNP with IC50 of 0.5 nM, but did not affect the sGC activated by YC-1 as well as basal sGC activity. SNP and YC-1 synergistically increased intracellular cGMP levels in rabbit corpus cavernosum smooth muscle cell cultures. YC-1 significantly relaxed rabbit cavernosum tissue strips in organ baths with an EC50 of 8.4 microM. In the presence of L-nitroarginine methyl ester to block endogenous NO production, co-administration of SNP shifted the dose response of YC-1 to the left, showing the synergism of SNP and YC-1 in tissue strips. In view of the clinical efficacy of phosphodiesterase-5 inhibitors, activation of sGC may provide an alternative means for enhancing the activity of neurally derived NO during sexual stimulation in the corpus cavernosum, representing a novel approach for the treatment of erectile dysfunction.

Macroscopic behavior of solids is widely studied from microscopic viewpoints such as molecular dynamics and lattice dynamics. However, there are some difficulties with the averaging methods in the microscopic expressions of stress, higher-order stress and heat flux. In this study, we discuss the microscopic expressions of macroscopic variables and macroscopic balance equations of a solid that is modeled as an assembly of atoms, on the basis of generalized Cosserat continuum theories. The concept of mesodomain is introduced to relate microscopic quantities of atoms to macroscopic quantities of continua. Microscopic expressions of stresses and heat flux are described as area averages of microscopic quantities such as velocities of atoms, interatomic potential forces. Balance equations for stress and higher-order stresses are derived from the equations of atomic motion. The energy equation, represented by the averages for the values in the mesodomain, is obtained by dividing the velocity of atoms into macroscopic motion and thermal motion. Since the generalized polar effects are taken into account in this model, derived macroscopic balance equations have the same form as the equations of generalized Cosserat continua. Moreover, microscopic descriptions obtained here show that the higher-order mechanical power of the generalized Cosserat continua is equivalent to the thermodynamic quantities of simple materials. The values of velocities of atoms calculated by molecular dynamics simulation are substituted into the newly obtained microscopic expressions of stress and higher-order stresses. The obtained values of stresses and the theoretical values derived from Eringen's formula correspond well, which demonstrates the usefulness of the present microscopic expressions for the practical application in computer simulations.

To elucidate the mechanism of propofol-induced pain on injection, we performed several studies using nafamostat mesilate, a kallikrein inhibitor, or lidocaine. As both pretreatment and low-dose mixing with nafamostat produced the same effects on pain reduction, we used the latter method in the following experiments. Low-dose mixing had the same effect on injection pain as mixing with lidocaine. The extent of pain was assessed by measuring bradykinin concentrations by mixing with blood. Propofol and its lipid solvent mixed with blood produced approximately two-fold generation of bradykinin compared with the saline control, and this was inhibited completely by nafamostat and lidocaine. Injection of the lipid solvent before propofol significantly aggravated pain compared with prior injection of saline, although the lipid solvent injected twice caused no change in pain. These results suggest that the lipid solvent for propofol activates the plasma kallikrein-kinin system and produces bradykinin which modifies the injected local vein. This modification of the peripheral vein may increase the contact between the aqueous phase propofol and the free nerve endings of the vessel, resulting in aggravation of propofol-induced pain.

Nonspecific responses of Japanese eels to environmental stress were monitored by assaying various lytic activities in eel epidermal extract. In fish maintained at 10 and 30 °C for up to 10 days, epidermal proteolytic activities due to serine protease and aminopeptidase and hemolytic activity varied within a 2-fold value range. Other proteolytic activities, due to cathepsins B and L, in the fish at 30 °C increased for up to 8 days and were 3.4 and 2.9-fold over those in fish maintained at 10 °C, respectively. This was accompanied by a 3.0-fold increase in bacteriolytic activity. Other forms of stress were exerted on the fishes by immersing them in a suspension of Flavobacterium columnare or giving them intraperitoneal injections of Edwardsiella tarda over 72 h. Although serine protease and aminopeptidase activities and hemolytic activity in the fishes exposed to F. columnare changed marginally, and were similar to those in the control fish, cathepsins B and L activities in the infected fishes increased more than 1.5-fold over their initial values over a 48 h period, along with a 4.5-fold increase in bacteriolytic activity. No marked change was detected in any of the lytic activities of the fishes exposed to E. tarda. These findings indicate that epidermal cathepsins B and L probably participate in bacteriolysis associated with Japanese eel skin and that their activities are elicited by environmental stimuli and may be an important nonspecific response of eels. Abbreviations: Cbz – carbobenzoxy; MCA – 4-methylcoumaryl-7-amide.

Nitric oxide (NO) has an important role in the pulmonary vasodilatation associated with the transition from fetal to neonatal life. NO activates pulmonary soluble guanylate cyclase (sGC), an obligate heterodimer composed of alpha1- and beta1-subunits, increasing synthesis of guanosine 3',5'-cyclic monophosphate (cGMP) and leading to vasodilation. In this study, regulation of sGC subunit expression during pulmonary development was examined. RNA blot hybridization revealed abundant alpha1- and beta1-subunit mRNA in lungs of late-gestation fetal and neonatal Sprague-Dawley rats, with markedly reduced levels detected in adult lungs. Pulmonary sGC enzyme activity in the presence of 1 mM sodium nitroprusside, a NO-donor compound, was approximately sevenfold greater in 1- and 8-day-old rats than in adult rats (P < 0.03). With the use of immunoblot techniques, pulmonary alpha1-subunit concentrations closely correlated with mRNA levels. With in situ hybridization, alpha1- and beta1-subunit mRNAs were readily detected in pulmonary vascular and bronchial smooth muscle cells as well as alveolar and serosal epithelial cells in lungs of 1-day-old rats. In adult lungs, sGC subunit mRNAs were present at low levels and were found nearly exclusively in bronchial and vascular smooth muscle cells. These results demonstrate that abundant pulmonary sGC is available to respond to the increased NO produced during the perinatal period. High-level expression of sGC subunit genes outside the vasculature of lungs of 1-day-old rats suggests an important role for NO-cGMP signal transduction in the perinatal regulation of pulmonary epithelial function and bronchial tone.

A fluorescent-sensitive assay was used to demonstrate the protease activity in the dorsal skin of Japanese eel (Anguilla japonica). Two distinct extracts were separately prepared from skin mucus and epidermal cell layers, with no mutual contamination. The epidermal extract was sensitive to various substrates, whereas there was no, or only marginal, susceptibility to the same substrates for the mucous extract. Optimum hydrolysis pHs of the epidermal extract was variable and below pH 7.0, and the optimum hydrolysis temperatures were between 40 and 50 °C. In addition, Tos-Phe-Ch2Cl, chymostatin, CdCl2, CuCl2, HgCl2 and ZnCl2 inhibited protease activities to different extents. Several other reagents specifically affected the protease activities, and their induced effects were useful for the identification of epidermal proteases. The findings indicate that a proteolytic factor, exhibiting various enzymological specificities, is retained within epidermal cell layers of Japanese eel. This factor is composed of 4 distinct proteases, such as cathepsins L and B-like proteases, a serine protease and an aminopeptidase.

Three isozymes of nitric oxide (NO) synthase (EC 1.14.13.39) have been identified and the cDNAs for these enzymes isolated. In humans, isozymes I (in neuronal and epithelial cells), II (in cytokine-induced cells), and III (in endothelial cells) are encoded for by three different genes located on chromosomes 12, 17, and 7, respectively. The deduced amino acid sequences of the human isozymes show less than 59% identity. Across species, amino acid sequences for each isoform are well conserved (> 90% for isoforms I and III, > 80% for isoform II). All isoforms use L-arginine and molecular oxygen as substrates and require the cofactors NADPH, 6(R)-5,6,7,8-tetrahydrobiopterin, flavin adenine dinucleotide, and flavin mononucleotide. They all bind calmodulin and contain heme. Isoform I is constitutively present in central and peripheral neuronal cells and certain epithelial cells. Its activity is regulated by Ca2+ and calmodulin. Its functions include long-term regulation of synaptic transmission in the central nervous system, central regulation of blood pressure, smooth muscle relaxation, and vasodilation via peripheral nitrergic nerves. It has also been implicated in neuronal death in cerebrovascular stroke. Expression of isoform II of NO synthase can be induced with lipopolysaccharide and cytokines in a multitude of different cells. Based on sequencing data there is no evidence for more than one inducible isozyme at this time. NO synthase II is not regulated by Ca2+; it produces large amounts of NO that has cytostatic effects on parasitic target cells by inhibiting iron-containing enzymes and causing DNA fragmentation. Induced NO synthase II is involved in the pathophysiology of autoimmune diseases and septic shock. Isoform III of NO synthase has been found mostly in endothelial cells. It is constitutively expressed, but expression can be enhanced, eg, by shear stress. Its activity is regulated by Ca2+ and calmodulin. NO from endothelial cells keeps blood vessels dilated, prevents the adhesion of platelets and white cells, and probably inhibits vascular smooth muscle proliferation.

Fish skin contains a variety of humoral defence lysins which have an integral role in fish immunity because of the ability of these proteins to destroy invading substances ( Alexander & Ingram 1992). These lysins generally comprise bacteriolysins, proteolysins and haemolysins. The lysins seem to be either individually or cooperatively stimulated to respond to pathogenic infection and environmental stress, such as ionic, osmotic, thermal and pollution stress ( Shephard 1994; Rice, Kergosien & Adams 1996; Bly, Quiniou & Clem 1997). There have only been a few reports on these lysins ( Al-Hassan, Thomson, Ali & Criddle 1987; Aranishi, Mano, Nakane & Hirose 1998). The present paper describes thermal effects on defence lysis, such as proteolysis, bacteriolysis and haemolysis, in the skin of the European eel, Anguilla anguilla L.

We have already proposed a triple tuned voltage controlled oscillator (VCO) for achieving an ultra-wideband characteristic. The fabricated VCO in C-Ku band has achieved the oscillation bandwidth of 5.6 GHz-16.8 GHz. In this paper, for achieving the wide oscillation bandwidth in the higher frequency band, we proposes a VCO that consists of a MMIC working as an active circuit and external hyper-abrupt junction varacter diodes connect to the MMIC with Au wires. The fabricated VCO in X-K band achieves the oscillation bandwidth of 9.9 GHz-21.9 GHz and the phase noise of -109.4 dBc/Hz +/-2.4 dB at 1 MHz offset from the carrier. In addition, it is shown that the fabricated VCO achieves the widest oscillation bandwidth and the lowest phase noise in X-K band compared with other reported wideband VCOs.

This article discusses the role and methodology of disease surveillance, which provides epidemiological data to formulate actions to control or eliminate disease hazard, one of the indispensable systems in national and global public health intelligence services. The target diseases include not only infectious diseases but also noncommunicable diseases as well as accidents and injuries. Efficacy is increasing with ever-newer diagnostic technology as well as expanding information technology. A few experiences in how surveillance has played an essential role in disease control are illustrated.

Complementary DNA clones corresponding to the 70- and 82-kDa subunits of soluble guanylate cyclase of rat lung have been isolated. Blot hybridization of total poly(A)+ RNA from rat tissues detected mRNA of about 3.4 kilobases for the 70-kDa subunit and about 5.5 kilobases for the 82-kDa subunit. Messenger RNA levels of both subunits were abundant in lung and cerebrum, moderate in cerebellum, heart, and kidney, and low in liver and muscle, consistent with previously described enzyme activities in these tissues. Southern blot analysis of high molecular weight genomic DNA from rat liver indicated that the genes for the 70- and 82-kDa subunits are different. The carboxyl-terminal region of the 70- and 82-kDa subunits showed a high degree of homology and also had a partial homology with the putative catalytic domain of particulate guanylate cyclase and adenylate cyclase, indicating that both the 70- and 82-kDa subunits have catalytic domains. The cDNAs were subcloned to an expression vector and transfected to L cells. The cells transfected with cDNA of the 70-kDa subunit or the 82-kDa subunit showed no guanylate cyclase activity, whereas the cells transfected with both the 70- and 82-kDa subunit cDNAs showed significant guanylate cyclase activity that was activated markedly by sodium nitroprusside. These data suggest that both subunits are required for both the basal catalytic and regulatory activity of soluble guanylate cyclase. Presumably both catalytic subunits must be present and interactive to permit synthesis of cyclic GMP and nitrovasodilator activation.

Ten years have passed since the start of operation of CEPCO's on-line TSC system in 1995. This paper reports on the results of our evaluation of the actual performance of the system. Using the actual performance data, we intend to clarify the various merits of the system as listed below: 1) Improvement of TTC (total transfer capability) through elimination of transient stability limitations; 2) selectability of ideal power shedding; and 3) reliability improved by configuration of different maker systems.

193-nm lithography is moving from the pre-production to the mass production phase and its target node is shifting from 90 nm to 65 nm. And now the ArF-immersion technology is spotlighted as the enabling technology for below 45nm node1). 157nm lithography is still important for next generation node below 45 nm as backup technology2). Gigaphoton has already released G40A (20W, 0.35pm) in 2001, G41A (20W, 0.30pm)3) in 2002, G42A (20W, 0.25pm)4) in 2003 to the advanced lithography market. On the other hand, since 1998 we have been developing high power 157nm light source for micro lithography with injection lock technology in research phase5)6). We have demonstrated a 30W, 0.12pm, @157nm line narrowed light source for microlithography with "Injection lock technology"1)2). Based on this injection lock technology, we have successfully developed "GigaTwin", a high power injection lock laser platform for 193nm lithography system. We have already released a high power ultra narrowed ArF laser "GT40A" (45W, 4000Hz, 11.25mJ, 0.18pm), with the GigaTwin platform.© (2005) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

This paper describes a wide-band voltage controlled oscillator (VCO) with the triple oscillation bandwidth and a better flatness of the phase noise in the oscillation bandwidth using triple varactor-tuned circuits. Altering capacitances of varactor diodes connected to every ports of a HBT in the same direction, the oscillation bandwidth of more than 1.5 octaves has been obtained. A fabricated VCO employing the triple-tuned circuits and a GaAs HBT has covered 1.56 octaves bandwidth achieving the phase noise of -114.9 dBc/Hz /spl plusmn/2.9 dB at 1 MHz offset from the carrier and the output power of 3.4dBm /spl plusmn/2 dB in C-Ku band.

Background. Combination therapy with doxorubicin (DOX) and docetaxel (DOC), given 3 weeks apart, is one of the standard regimens used for treating metastatic breast cancer, but it frequently generates febrile neutropenia. To find a safer regimen with less myelotoxicity and the appropriate dose intensity, we conducted a phase I study of simultaneous weekly infusion with DOX and DOC. Methods. Twenty-five patients with advanced breast cancer were treated with an intravenous push-injection of DOX that was immediately followed by a 1-h infusion of DOC. This was repeated every week for at least 6 weeks. The premedication employed was three 4-mg doses of dexamethasone every week. Patients were divided into four groups for which the doses of DOX and DOC were escalated in 5-mg/m2 increments. Results. In the 18 patients who were treated with DOX 15 or 20 mg/m2 and DOC 25 mg/m2, or lower, the regimen was found to be tolerable, without febrile episodes. The regimen with 20 mg/m2 of DOX and 30 mg/m2 of DOC was the maximum tolerated dose. Other indications of grade 3 toxicity included asthenia in 4% of patients, anorexia in 8%, and vomiting in 8%. Of the 25 patients, 14 had a partial response. The overall response rate was 56% (95% confidence interval [CI] , 35% to 77%). The recommended dose for further trial was 20 mg/m2 of DOX and 25 mg/m2 of DOC. Conclusion. Simultaneous weekly infusion with DOX and DOC was feasible, with modest neutropenia and preserved dose intensity. This regimen may be helpful in the management of patients with advanced breast cancer.

L-PDMP (L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol) exhibits stimulatory effects on glycosphingolipid biosynthesis and its neurotrophic actions in cultured neuron. The effects of intraperitoneal administration of L-PDMP on sphingolipid metabolism and behavioral changes in the rat following permanent occlusion of the left middle cerebral artery (MCA) were investigated. The L-PDMP treatment induced increases in glucosylceramide (ganglioside precursor) and sphingomyelin (SM) levels in the ischemic cerebral cortex, and improved acquisition of memory and learning in the Morris water maze task. The pharmacological effects of L-PDMP have been proposed to have a significant activity on promoting cell survival and improving neural functions.

Soluble guanylate cyclase (sGC) is an important enzyme in corpus cavernosum smooth muscle cells as it is one of the regulators of the synthesis of cGMP. The efficacy of sildenafil (Viagra) in the treatment of male erectile dysfunction indicates the importance of the cGMP system in the erectile response as the increased levels of cGMP induce relaxation of the corpus cavernosum. sGC is physiologically activated by nitric oxide (NO) during sexual stimulation, and its activity can be pharmacologically enhanced by several NO-donors. Agents like YC-1 can also activate sGC after binding to a novel allosteric site in the enzyme, a site different from the NO binding site. YC-1 can relax rabbit cavernosal tissue and it facilitates penile erection in vivo. This review summarizes the enzymology, biochemistry and pharmacology of this novel allosteric site and its relevance for the regulation of penile function. This type of sGC activators represent a new class of compounds with a different pharmacological profile in comparison to the classical NO-donors and they could be beneficial for the treatment of male erectile dysfunction.

We compared the efficacy of ACD-CPR and STD-CPR based on 64 multi-institutional reports. No significant differences were observed in the rate of restoration of spontaneous circulation (ROSC) and in cardiopulmonary parameters during CPR using the two methods. There were 5 cases in which cardiopulmonary parameters improved after switching from STD-CPR to ACD-CPR and, eventually, in two of them spontaneous circulation was restored. In the ROSC cases of both groups, ETCO2 and values of SpO2, PaO2, and systolic BP at 30 minutes were higher than those of non-ROSC cases. ETCO2 never exceeded 20 mmHg in the non-ROSC cases, but it was higher in the ROSC cases. ACD-CPR is a good choice when trained persons are present or when extra hands are available to continue the CPR.

BACKGROUND AND PURPOSE: Focal cerebral ischemia results in neuronal changes in remote areas that have fiber connections with the ischemic area. We reported previously that a high-signal-intensity lesion was observed in the substantia nigra after striatal infarction on T2-weighted MR images in both clinical and experimental cases. However, the origin of these changes in signal intensity remains unclear. The aim of this study was to investigate the nigral changes by examining the correlation between the apparent diffusion coefficient (ADC) and the tissue structure. METHODS: Sprague-Dawley rats were subjected to middle cerebral artery occlusion. Four days after the occlusion, when T2-weighted images revealed the presence of an area of high signal intensity in the ipsilateral substantia nigra, diffusion-weighted imaging was performed using a 4.7-T superconductive MR unit, and the ADCs were calculated and imaged. Histopathologic examination by both light and electron microscopy was performed on day 4 after surgery. RESULTS: Diffusion-weighted images showed an area of high signal intensity in the ipsilateral substantia nigra, and the ADC map revealed uniform reduction of the ADC in this area. Swelling of astrocytic end-feet was observed, especially in the pars reticulata. CONCLUSION: These findings suggest that MR changes in the ipsilateral substantia nigra after striatal injury consist mainly of swelling in the astrocytic end-feet.

The global polio eradication program is under way with the target year of 2000. We reviewed the program progress, in perspective, from the experience of the global smallpox eradication, which is at present a sole disease ever eradicated by orchestrated global efforts. We concluded that despite substantial efforts being made by the World Health Organization and member states with the current progress, it would require additional some three years, namely 2002. This would safe-guard the success. As of January 2000, there are still at least 22 endemic states in Indian Subcontinent and sub-Saharan Africa. Experiences in smallpox eradication, although the disease is different, indicated that to stop transmission in such a large number of endemic states took more than three years, assuming that further support would come toward the final goal.

To estimate the length of hospitalization following bone marrow transplantation(BMT), we conducted a retrospective study of 190 patients who had received allogeneic BMTs at our institution. By our criteria, patients were considered ready for discharge if they were afebrile, did not need intravenous chemotherapy or blood transfusions more than 2 times per week, had maintained these conditions for 1 week or more, and also had no medical history of hepatic veno-occlusive disease, grade-II-or-higher graft-versus-host disease, interstitial pneumonitis, or severe hepato-renal dysfunction. The median length of hospitalization was 108.5 days. Of 82 patients who satisfied our discharge criteria by their 70th hospital day, 10 experienced mild complications during the next 30 hospital days. Of 89 patients who were considered ready for discharge by the 40th hospital day, 30 and 38 experienced complications during the next 30 and 60 hospital days, respectively, and 16 required emergency treatment. No significant baseline characteristics distinguished the patients who experienced complications from those who did not, either after 40 or 70 hospital days. This compounded the difficulty of predicting the development of complications in patients who satisfied our discharge criteria. Although management on an outpatient basis should be safe and feasible for BMT patients who meet our discharge criteria by the 70th day of hospitalization, caution is advised for early discharges after only 40 hospital days.

This report describes a patient with acute-type adult T cell leukemia/lymphoma (ATLL) successfully treated by autologous CD34+ peripheral blood stem cell transplantation after fractionated total body irradiation and high-dose cytarabine and cyclophosphamide. A newly established inverse polymerase chain reaction method was used to demonstrate the disappearance of ATLL clonal cells. The patient achieved a sustained molecular remission after transplantation, but died from opportunistic infection 4 months after transplantation. Thus, autologous CD34+ peripheral blood stem cell transplantation is promising for this type of malignancy. However, a prudent clinical attitude toward immunological fragility after transplantation is needed for better outcome.

We experienced three patients with partial intramural coronary artery diagnosed preoperatively. We gave balanced anesthesia using narcotics and non-narcotic analgesics for non-cardiac surgery, administering phenylephrine against hypotension. The anesthetic course was relatively stable. According to the special pathophysiology of this disease, tachycardia and hypotension associated with anesthesia should be avoided, and special caution is needed when nitroglycerine is used due to its adverse effect on systolic narrowing of the coronary artery.

To clarify the correlation between the histopathological findings and MR signal intensity of the cyst wall, fifteen cystic metastatic brain tumors of eleven patients were imaged using a 0.5T MR unit just before surgery, and the MRI findings were correlated with the histopathological findings of resected lesions. On T2-weighted images, all cyst walls showed hypointensity. On T1-weighted images, the intensity of the cyst wall could be classified into three groups, compared with the cerebral cortex. Walls with hyperintensity on T1WI(group H; n = 6) consisted of ample tumor cells, blood vessels and connective tissues, suggesting viable tumor cells. Iso-intense walls on T1W1(group I; n = 3)had abundant reactive glial tissues. Hypointense walls on T1W1 (group L; n = 5)revealed hemorrhage and/or hemosicerin in the wall, suggesting hemorrhagic necrosis. Thus a good correlation was demonstrated between the MR signal intensities and histopathological findings of cyst walls of cystic metastatic brain tumors. This may contribute not only to more precise diagnosis on MRI but also to more planning for treatment of cystic brain metastases.

Three isozymes of nitric oxide synthase (NOS) have been identified, cDNAs isolated and sequenced, and antibodies produced against each isozyme. Isozyme I (found primarily in central and peripheral neuronal cells), II (in cytokine-induced cells), and III (in endothelial cells) show less than 58% identity in the deduced amino acid sequences from humans. Many investigators have produced isozyme-specific antibodies and used these antibodies to locate these proteins in various cells and tissues. NOS-I is constitutively expressed, and the enzymatic activity is regulated by Ca2+ and calmodulin. The anti-NOS-I antibodies have allowed investigators to characterize non-adrenergic non-cholinergic neurons as nitrergic neurons, revealed NOS-I immunoreactivity in neurons and macula densa cells of the kidney and pancreatic islet cells, human skeletal muscle, and to demonstrate that various structures within the brain and spinal cord contain NOS-I. NOS-II is not regulated by Ca2+ and has been implicated in the pathophysiology of sepsis and autoimmune diseases. The anti-NOS-II antibodies have localized this isoform to infiltrating macrophages in pancreatic islets of diabetic rats, infiltrating macrophages and myocytes of a transplant heart model in rats, various cell types in bacterially and endotoxin-treated rats, alveolar macrophages in areas of inflammation in humans, and vascular smooth muscle cells of human atherosclerotic aneurysm. Isoform III is similar to NOS-I in that it is constitutively expressed and regulated by Ca2+ and calmodulin. Anti-NOS-III antibodies have found that this isoform is relatively specific for endothelial cells.

Nitric oxide (NO) is a biological mediator that, when produced by the type II (inducible) nitric oxide synthase (NOS), has been implicated in the pathophysiology of inflammatory diseases. To examine this putative role of NO, pleural inflammation was elicited in rats by the intrapleural injection of carrageenan (1 mg). A pleural exudate and cellular influx developed, which peaked at 24 h and generally resolved by 72 h. The cellular influx was primarily composed of polymorphonuclear cells during the first 24 h, followed by macrophages during the subsequent 24 h. Inflammatory cell-associated NOS activity and pleural exudate nitrite (NO2-) + nitrate (NO3-) (NOx) also increased, peaking at 6 h and 24 h, respectively. Cell-associated NOS activity was calcium-independent, indicating the presence of the type II NOS isoform; NOS activity in the pleural cavity and polymorphonuclear cells influx were temporally correlated. Administration of L-NG-monomethylarginine (L-NMA) (200 mg/kg/day) attenuated the pleural exudation, cellular influx, pleural exudate NOx, and cell-associated NOS activity. The relative composition of the pleural cavity cellular infiltrate was not changed by L-NMA, indicating the influx of individual cell types were affected equally. L-Arginine (500 mg/kg/day) completely prevented the effects of L-NMA on pleural exudation and cellular influx and partially prevented the inhibition of pleural exudate NOx accumulation by L-NMA. These data implicate NO as a modulator of the pleural inflammatory response and support a future clinical role for NOS inhibitors in the treatment of inflammatory disease.

We have identified two novel potent and selective inhibitors of inducible nitric oxide synthase, S-ethylisothiourea and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine. Ki values of 14.7 nM for S-ethylisothiourea and 4.2 nM for 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine were obtained with partially purified preparations of inducible nitric oxide synthase. These compounds demonstrate about 1000-fold greater potency than prototypical inhibitors, and the inhibitions are 10-40-fold more selective for murine inducible nitric oxide synthase, compared with the rat neuronal and bovine endothelial isoforms of nitric oxide synthase. These compounds also potently inhibit the nitric oxide synthase activity in intact J774 mouse macrophages. The inhibition is competitive with the substrate L-arginine and reversible in both enzymatic and intact cell assays. These potent and selective inhibitors of inducible nitric oxide synthase may have potential therapeutic applications in the treatment of inflammatory and autoimmune diseases.

To determine the normal CT appearances of the subarcuate fossa and petromastoid canal, the 136 temporal bones of 68 patients, without injuries or anomalies, were scanned with high-resolution CT. The subarcuate fossa was visualised in 48.6%. The average width of the fossa was 8.3 mm (SD 3.1) and the depth 1.9 mm (SD 0.6). The petromastoid canal was visualised in 48.6%. The diameter of the canal was 0.6 mm, (SD 0.1) and the total length was 9.3 mm (SD 1.7). The canal connected the subarcuate fossa and the mastoid antrum with the appearance of an anteriorly convex curve, 15.6° (SD=12.2) anteriorly then bent 44° (SD= 16.0) posteriorly. In the coronal plane, the canal inclined 2.9° (SD = 6.3) from the horizontal plane. It is important to understand these structures to diagnose fracture and to estimate the pathological nature of the intracranial spread of mastoiditis.

Coronal and axial planes in cervical MR angiography (MRA) were compared to determine which plane is more useful in the diagnosis of the vertebral and subclavian arteries. MRA was obtained in 18 patients with symptoms suggestive of arteriosclerosis using a 1.0 T MR unit with a coil designed for cervical MRA. Each artery was classified into categories based on the visualisation of the artery including the branch point of the vertebral artery. The number of cases in which the branch point was visualised was as follows (coronal/axial): right subclavian artery, 18/16; left subclavian artery, 14/16; right vertebral artery, 15/15; left vertebral artery, 12/16. The ability to visualise branch points was a little higher on the axial plane, but the difference was minimal. Considering that coronal MRA can visualise the total length of cervical artery, coronal MRA seems to be better than axial MRA.

The congenital hypothalamic hamartoma or hamartoblastoma syndrome (CHHS) is a rare complex malformation. We report a case of CHHS studied by CT, MRI and angiography.

We reviewed 24 patients with intracranial vertebral artery dissections treated during the last 12 years. Sixteen patients were admitted with subarachnoid hemorrhage (SAH) and 8 did not have SAH. The mean age at the time of onset was 50.0 years. Male preponderance was noted. Among 21 patients with acute onset, 6 (29%) experienced prodromal neck pain and 3 (60%) of 5 SAH patients showed nuchal stiffness when examined within 6 hours of onset. The preoperative angiographical findings were uniform in SAH cases in contrast to the varied angiographical findings seen in non-SAH cases. So-called pearl and string sign was observed in most SAH cases, but the "string" was often so short and wide that the term "constriction" appeared more suitable. From intraoperative observations, the angiographical point of constriction seemed to represent the proximal or distal end of dissection. As for treatment, 19 patients underwent 20 surgeries. Trapping was performed in eight surgeries, base clipping was performed in five, and proximal clipping was performed in seven. Both trapping and base clipping prevented further bleeding, but trapping was associated with a high rate of postoperative lower cranial nerve palsy. Postoperative neurological complications were less frequent after proximal clipping, but subsequent postoperative bleeding occurred in one patient treated by this technique. The overall long-term outcome in the surgically treated cases in our series was favorable, but most patients suffered from various degrees of uncomfortable dysphagia or hoarseness for some period after surgery. It was also noted that, in half of the disabled cases, the major disability was attributable to lower cranial nerve palsy and respiratory troubles that developed postoperatively.

The cloning of particulate and soluble guanylyl cyclases is summarized in Table I. With respect to transmembrane signal transduction systems, guanylyl and adenylyl cyclases can be grouped together with some protein tyrosine kinases and protein tyrosine phosphatases to form a diverse protein family with various structural and functional similarities (Garbers, 1989, 1991, 1992; Koesling et al., 1991; Chinkers and Garbers, 1991; Fig. 1). Particulate guanylyl cyclase contains a single transmembrane domain, and the peptide-binding portion (ligand receptor) is on the exterior surface and the catalytic region on the interior, similar to the protein tyrosine kinase/receptor and the protein tyrosine phosphatase/receptor families (Yarden et al., 1986; Charbonneau et al., 1988; Tonks et al., 1988). Protein tyrosine kinases and phosphatases are also activated by ligand binding to the extracellular domain, which in turn results in phosphorylation or dephosphorylation. On the other hand, soluble guanylyl cyclase exists as a heterodimer with two putative catalytic domains, and both subunits are essential for enzyme activity and activation by nitric oxide. It is thus particularly interesting that adenylyl cyclase also contains two catalytic domains, which are both necessary for catalytic activity (Tang et al., 1991). It is possible that particulate guanylyl cyclase may also dimerize on hormonal stimulation and two catalytic domains from two monomers form a functional catalytic center capable of forming cyclic GMP. The catalytic core of GC-A expressed in bacteria was shown to form a homodimer with positively cooperative kinetics (Thorpe et al., 1991). The physiological significance of the existence of multiple forms of soluble guanylyl cyclase subunits remains unclear. Future studies should reveal the differences in tissue distribution and activation by nitrovasodilators in various heterodimers of soluble guanylyl cyclase.