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Comparar las dosis de radiación en las gónadas con y sin protector gonadal y optimizar el uso de estos protectores al realizar radiografías de tórax a lactantes.

Occupational exposure of radiation workers, including nurses, is an important issue that should always be considered. However, there are limited reports on external exposure of nurses working in nuclear medicine investigated using a personal dosimeter with a trend function. We investigated the relationship between the personal dose equivalent and behavior of nurses in nuclear medicine using a personal dosimeter with a trend function. It was found that the external exposure of nurses was high when they cleaned hospital rooms where patients who received radiopharmaceutical drugs were admitted. However, none of the nurses surveyed exceeded 3μ. Visualization of the contamination in the hospital room showed that the area around the sink and trash can was particularly contaminated. Hence, nurses need to be more careful when cleaning. Although it is unlikely that the nurses surveyed will be affected by external exposure, data in this report is valuable for nurses at medical institutions to consider work hours and personnel strategies.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3–4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibits lung fibrosis by direct administration into the lung by intranasal route. Pulmonary fibrosis was induced with bleomycin and RNA therapeutics was administered during both acute and chronic phases of the disease. The levels of periostin and transforming growth factor-β1 in airway fluid and lung tissue, the deposition of collagen in lung tissue and the lung fibrosis score were significantly reduced in mice treated with siRNA and antisense against periostin compared to control mice. These findings suggest that direct administration of siRNA or antisense oligonucleotides against periostin into the lungs is a promising alternative therapeutic approach for the management of pulmonary fibrosis.

We describe the fabrication and evaluation of a nail-deformation haptics actuator having a flexible haptics film. The novelty of the developed actuator is the generation of a vibration that directly deforms the nail and finger pad. The flexible piezo-MEMS film is fabricated adopting ultra-thin lead-zirconate-titanate microelectromechanical system (MEMS) and lamination technology. The flexible piezo-MEMS film has flexibility (thickness: 65 µm) and low weight (mass: 55 mg). The device can thus be attached on a nail without discomfort. A nail-deformation haptics actuator was fabricated by attaching this flexible piezo-MEMS film on an artificial nail. When applying a DC voltage of 40 V to the film, there was a strain of -36.5 × 10-6in the cylindrical direction of the nail and -12.1 × 10-6in the circumferential direction. Furthermore, applying an AC voltage (40 Vpp, 20 Voffset) at a frequency of 200–300 Hz, the finger pad deformed sufficiently to perceive vibration.

We present an analysis of new Suzaku data and archival data from XMM-Newton of the cluster of galaxies Sérsic 159-03, which has a strong soft X-ray excess emission component. The Suzaku observation confirms the presence of the soft excess emission, but it does not confirm the presence of redshifted $\ion{O}{vii}$lines in the cluster. Radial profiles and 2D maps derived from XMM-Newton observations show that the soft excess emission has a strong peak at the position of the central cD galaxy and the maps do not show any significant azimuthal variations. Although the soft excess emission can be fitted equally well with both thermal and non-thermal models, its spatial distribution is neither consistent with the models of intercluster warm-hot filaments, nor with models of clumpy warm intracluster gas associated with infalling groups. Using the data obtained by the XMM-Newton Reflection Grating Spectrometers we do not confirm the presence of the warm gas in the cluster centre with the expected properties assuming the soft excess is of thermal origin. The observed properties of the soft excess emission are consistent with the non-thermal interpretation. While the high density of relativistic electrons associated with the peak of the soft emission in the cluster centre might have been provided by an active galactic nucleus in the central cD galaxy, the underlying population might have been accelerated in diffuse shocks.

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ZFP521was previously identified as a putative gene involved in induction of B-cell lymphomagenesis. However, the contribution of ZFP521to lymphomagenesis has not been confirmed. In this study, we sought to elucidate the role of ZFP521in B-cell lymphomagenesis. To this end, we used a retroviral insertion method to show that ZFP521was a target of mutagenesis in pre-B-lymphoblastic lymphoma cells. The pre-B-cell receptor (pre-BCR) signaling molecules BLNK, BTKand BANK1were positively regulated by the ZFP521gene, leading to enhancement of the pre-BCR signaling pathway. In addition, c-mycand c-junwere upregulated following activation of ZFP521. Stimulation of pre-BCR signaling using anti-Vpreb antibodies caused aberrant upregulation of c-mycand c-junand of Ccnd3, which encodes cyclin D3, thereby inducing the growth of pre-B cells. Stimulation with Vpreb affected the growth of pre-B cells, and addition of interleukin (IL)-7 receptor exerted competitive effects on pre-B-cell growth. Knockdown of BTKand BANK1, targets of ZFP521, suppressed the effects of Vpreb stimulation on cell growth. Furthermore, in human lymphoblastic lymphoma, analogous to pre-B-cell lymphoma in mice, the expression of ZNF521, the homolog of ZFP521in humans, was upregulated. In conclusion, our data showed that the ZFP521gene comprehensively induced pre-B-cell lymphomagenesis by modulating the pre-B-cell receptor signaling pathway.

Bronchial asthma is characterised by airway inflammation and remodelling with a decline of lung function. Fibrocytes are bone marrow-derived mesenchymal progenitor cells that play important roles in the pathogenesis of airway remodelling. Several clinical parameters are currently being used in routine clinical practice to assess outcome of therapy in asthma including frequency of rescue with short-acting β2-agonist and the asthma control test. In this study, we hypothesised that asthma control test is associated with circulating levels of fibrocytes in bronchial asthma.

Alcohol consumption is a major cause of liver injury but the mechanisms are not completely understood. Protein S (PS) is an anticoagulant glycoprotein with multiple functions. The role of PS in liver injury is unknown.

Summary. Background:Activated protein C (APC) can regulate immune and inflammatory responses and apoptosis. Protein C transgenic mice develop less diabetic nephropathy but whether exogenous administration of APC suppresses established diabetic nephropathy is unknown.

Background:Activation of the complement system has been implicated in tumor growth. The antifibrinolytic protein, activated thrombin‐activatable fibrinolysis inhibitor (TAFIa), can modulate the activation of the complement system by inactivating the anaphylatoxins C3a and C5a. The apolipoprotein‐E (ApoE) genotype has been associated with carcinogenesis. Objective:The aim of this study was to evaluate whether TAFIa can affect the development of cancer in the ApoE‐deficient mouse model. Methods:TAFI and ApoE double‐knockout mice were generated. A group of mice was treated with the diabetogenic and carcinogenic compound streptozotocin (stz). Mice treated with saline, single knockout mice and wild‐type (wt) mice served as controls. Results:Six months after treatment with stz, mice were sacrificed. Hepatic tumors were found in male double‐knockout mice treated with stz but none was found in control animals that were not treated with stz or in single knockout of ApoE or wt animals. There was no significant difference in coagulation system activation between the groups of mice. The plasma concentrations of C5a, factor D and transforming growth factor‐β1 were increased in TAFI/ApoE double‐deficient mice treated with stz compared with the mice of the same genotype treated with saline. Conclusion:Apo‐E deficiency alone was not associated with tumors but the lack of TAFI appears to make the mice permissive for tumor formation in ApoE mice.

Background: The fibrinolytic system has been implicated in the pathogenesis of pulmonary hypertension (PH). Thrombin‐activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis and therefore its absence would be expected to increase fibrinolysis and ameliorate PH. Objective: The objective of the present study was to evaluate the effect of TAFI deficiency on pulmonary hypertension in the mouse. Methods and results: PH was induced in C57/Bl6 wild‐type (WT) or TAFI‐deficient (KO) mice by weekly subcutaneous treatment with 600 mg kg−1monocrotaline (MCT) for 8 weeks. PH was inferred from right heart hypertrophy measured using the ratio of right ventricle‐to‐left ventricle‐plus‐septum weight [RV/(LV+S)]. Pulmonary vascular remodeling was analyzed by morphometry. TAFI‐deficient MCT‐treated and wild‐type MCT‐treated mice suffered similar weight loss. TAFI‐deficient MCT‐treated mice had reduced levels of total protein and tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), transforming growth factor‐β (TGF‐β) and monocyte chemoattractant protein‐1 (MCP‐1) in bronchial alveolar lavage compared with wild‐type MCT‐treated mice. The ratio of RV to (LV+S) weight was significantly higher in WT/MCT than in KO/MCT mice. The pulmonary artery wall area and vascular stenosis were both greater in MCT‐treated WT mice compared with MCT‐treated TAFI‐deficient mice. Conclusions: TAFI‐deficient MCT‐treated mice had less pulmonary hypertension, vascular remodeling and reduced levels of cytokines compared with MCT‐treated WT animals, possibly as a result of reduced coagulation activation.

Objective:Protein S may exert an anticoagulant activity by enhancing the anticoagulant activity of activated protein C and/or by directly inhibiting the prothrombinase complex. Protein S itself may also directly regulate inflammatory responses and apoptosis. The role of protein S in acute lung injury (ALI) was unknown. This study evaluated the effect of protein S on ALI in the mouse. Methods:Animal ALI was induced in C57/BL6 mice by intratracheal instillation of lipopolysaccharide (LPS). Mice were treated with protein S or saline by intraperitoneal injection 1 h before LPS instillation. Results:Activated protein or protein S alone and combined activated protein C + protein S therapy decreased inflammatory markers and cytokines in mice with acute lung injury. In LPS‐treated mice compared with controls ALI was induced as shown by significantly increased levels of total protein, tumor necrosis factor‐α, interleukin‐6 and monocyte chemoattractant protein‐1 in the bronchoalveolar lavage fluid. Mice with ALI treated with protein S had significantly decreased concentrations of tumor necrosis factor‐α and interleukin‐6 in the lung compared with untreated animals. Thrombin‐antithrombin III, a marker of the activity of the coagulation cascade, was unchanged. Protein S inhibited the expression of cytokines in vitroand increased activation of the Axl tyrosine kinase pathway in A549 epithelial cells. Conclusion:Protein S protects against LPS‐induced ALI, possibly by directly inhibiting the local expression of inflammatory cytokines without affecting coagulation.

Background: Thrombin‐activatable fibrinolysis inhibitor (TAFI) has been reported to affect wound healing and fibrotic processes, but its role in renal tubulointerstitial fibrosis remains unknown. Objective: To study its potential role, we compared TAFI‐deficient and wild‐type mice for the degree of renal fibrosis caused by unilateral ureteral obstruction (UUO).Methods: The grade of tubulointerstitial fibrosis, the activity of plasmin, MMP‐2 and MMP‐9 were evaluated on days 4 and 9 after UUO. Results: The renal content of hydroxyproline and the activity of plasmin, MMP‐2 and MMP‐9 were significantly increased in kidneys with UUO from TAFI‐deficient mice compared with those from wild‐type mice. These differences disappeared when animals with UUO from both groups were treated with the plasmin inhibitor tranexamic acid. The renal concentrations of fibrogenic cytokines were also significantly elevated in kidneys with UUO from TAFI‐deficient mice compared with those from wild‐type mice. Conclusion: The results of this study suggest that increased renal activity of plasmin in TAFI‐deficient mice causes increased renal interstitial fibrosis in obstructive nephropathy.

To elucidate whether progressive wild-type transthyretin (TTR) deposition can actually occur after liver transplantation (LT), amyloid fibrils were investigated in two familial amyloid polyneuropathy patients with TTR Val30Leu variant, who died 1 year after LT. Amyloid fibrils were extracted from cardiac muscles, sciatic nerves and kidney, which were investigated by the immunoprecipitation-mass spectrometry method and liquid chromatography-ion trap mass spectrometry analysis. The ratio of wild-type to variant TTR in cardiac muscle was approximately 5:5 before LT, but greatly increased to about 9:1 after transplantation. The ratios in sciatic nerves and kidney obtained at autopsy were approximately 5:5. Wild-type TTR was undetectable in kidney amyloid obtained before LT. Our results indicate that paradoxical wild-type TTR deposition after LT can preferentially occur in myocardium, leading to fatal cardiac dysfunction, but it is quite likely that this phenomenon can also occur in other visceral organs.

The natriuretic peptide (NP) family is composed of three members: atrial, brain/ventricular and C-type NPs (ANP, BNP/VNP and CNP respectively) in tetrapods and teleostean fish, but only CNP in elasmobranch fish. In order to trace the process of divergence of the NP family in early vertebrate evolution, we attempted to detect NPs in the primitive ray-finned fish, the sturgeon (Acipenser transmontanus). Unexpectedly, we isolated four distinct NP cDNAs from the heart and brain of this chondrostean fish. The single NP from the brain was CNP, as judged from the lack of C-terminal 'tail' sequence extending from the intramolecular ring. Two of the three cardiac NPs were ANP and VNP, as judged by the presence of an amidation signal at its C-terminus (ANP) and a long and conserved C-terminal tail sequence (VNP) respectively. The third cardiac NP was most probably BNP because it possessed all the features characteristic of BNP including: (1) the presence of dibasic amino acids within the intramolecular ring; (2) the presence of AUUUA repeats in the 3'-untranslated region of its mRNA; (3) equivalent expression of its mRNA in the atrium and ventricle and appreciable expression in the brain. Based on the sturgeon BNP sequence, we further isolated BNP cDNA from the heart of tilapia and pufferfish for the first time in teleostean fish. Phylogenetic analysis of the precursors showed that newly identified NPs belong to each group of the four NPs. The current identification of both VNP and BNP in the sturgeon clearly showed that BNP and VNP are coded by distinct genes, and that the NP family consists of at least four members in the ray-finned fish. VNP has not been molecularly identified in mammals but its presence is suggested from physiological studies; heterologous fish VNP exhibited more potent vasorelaxant activity than homologous mammalian ANP in the isolated coronary artery of dogs.

CsBr phosphor ceramics doped with different luminescence center such as In203,EU203,EuC13, SmC13, TbC13,GdC13or NdC13as a candidate of a new photosimulable phosphor for medical x-ray imaging sensor are prepared using a conventional ceramic fabrication process. It is found that x-ray-irradiated Eu-doped CsBr (CsBr:Eu) exhibits intense photostimulated luminescence (P SL). The peak wavelength of the PSL emission and stimulation spectra of CsBr:Eu phosphor ceramic sample is 450 nm and 690 nm, respectively. The dependence of PSL properties on preparing conditions of phosphor ceramic samples,such as Eu concentration,sintering temperature and sintering time,is studied and the optimum preparing condition is also studied. It is found that the PSL intensity of CsBr:Eu phosphor ceramics fabricated under optimum preparation condition is higher than that of commercially available imaging plate usingBafBr:Eu.

Cytochrome P450 21-hydroxylase (P450c21) is a key enzyme for corticosteroidogenesis. To understand the regulatory mechanisms of cortisol production in fish, we have cloned a cDNA encoding P450c21, for the first time in non-mammalian vertebrates, from the head kidney of the eel (Anguilla japonica). The overall similarity of the deduced P450c21 sequence was modest (41-44% amino acid identity) between the eel and mammals. However, the functional domains for steroid-binding, heme-binding and proton-transfer sites were well conserved (74-100% identity). The eel P450c21 mRNA was expressed abundantly in the anterior quarter of the head kidney, but was undetectable in the remaining three-quarters or in other tissues including the gill, heart, liver, intestine, kidney, immature gonad and skeletal muscle. Functional expression of the cDNA clone in non-steroidogenic COS-1 cells produced a protein with high 21-hydroxylase activity to convert progesterone to 11-deoxycortisterone but not 17alpha-hydroxyprogesterone to 11-deoxycortisol, although the latter is a preferred substrate for mammalian P450c21. To examine whether 21-hydroxylated progesterone is actually 17alpha-hydroxylated in the eel interrenal, 11-deoxycorticosterone and (3)H-corticosterone were respectively incubated with the interrenal-containing anterior quarter of the head kidney. The separation of the steroids produced by two HPLC systems revealed that cortisol was produced from both substrates, showing the 17alpha-hydroxylation of 11-deoxycorticosterone and corticosterone in the eel interrenal. ACTH infused at 3 pmol/kg per min for 5 h consistently increased plasma cortisol levels and interrenal P450c21 mRNA levels in seawater eels. These results showed that the interrenal-specific eel P450c21 cloned in this study is involved in cortisol production through conversion of progesterone to 11-deoxycorticosterone in the interrenal-containing anterior quarter of eel head kidney. Furthermore, ACTH stimulates cortisol production in part through enhanced P450c21 expression in the eel interrenal.

Background & Aims: In this study, the effect of dietary glycine on experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS) and dextran sulfate sodium (DSS) in the rat was evaluated. Methods: Male Wistar rats were fed a diet containing 5% glycine or casein as controls starting 3 days before experiments, and were given a single intracolonic injection of TNBS (50 mg/rat, dissolved in 50% ethanol). Similarly, some rats were given 3% DSS orally in drinking water for 5 days to induce colitis as a second model. The severity of colitis was evaluated pathologically, and tissue myeloperoxidase (MPO) activity was measured. Further, mRNA and protein levels for interleukin (IL)-1@b, tumor necrosis factor (TNF)-@a, cytokine-induced neutrophil chemoattractant (CINC), and macrophage inflammatory protein (MIP)-2 were detected by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: A diet containing glycine ameliorated diarrhea and body weight loss caused by TNBS, and improved both macroscopic and histologic scores of colitis significantly. TNBS-induced increases in MPO activities in the colonic tissue were blunted significantly in glycine-fed animals. Further, dietary glycine largely prevented increases in IL-1@b and TNF-@a in the colon 2 days after TNBS, and TNBS induction of CINC and MIP-2 in the colonic tissue also was abrogated by glycine. Importantly, the protective effect of glycine was significant even when TNBS colitis was once established. Moreover, dietary glycine also was preventive in a second, DSS-induced colitis model. Conclusions: Dietary glycine prevents chemical-induced colitis by inhibiting induction of inflammatory cytokines and chemokines. It is postulated that glycine may be useful for the treatment of inflammatory bowel diseases as an immunomodulating nutrient.

In teleost fish and tetrapods, the natriuretic peptide (NP) family consists of ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide) and VNP (ventricular natriuretic peptide) that are secreted from the heart, and C-type natriuretic peptide (CNP) that is found in the brain. However, CNP is the only NP identified in the heart and brain of elasmobranchs, suggesting that it is the ancestral type of the NP family and that ANP, BNP and VNP appeared later in the vertebrate phylogeny. To delineate more clearly the molecular evolution of this hormone family, we determined the sequence of NP molecule(s) in evolutionarily the oldest vertebrate group, the cyclostomes. We have cloned a novel NP cDNA from the heart and brain of hagfish, Eptatretus burgeri, using the RACE method and degenerate primers that amplify all known types of NP cDNAs. The novel NP, named EbuNP after the scientific name of this hagfish, appears to be the only NP in the heart and brain, as no other NP cDNAs were amplified even after specific removal of the cloned EbuNP mRNA from the mRNA pool, except for a minor alternatively spliced EbuNP cDNA with a truncated 3'-untranslated sequence. The EbuNP was equally similar to known NPs but was not considered to be a CNP because of the presence of a C-terminal tail sequence. The EbuNP gene was abundantly expressed in the cardiac atrium, ventricle, portal heart and brain but scarcely in the intestine; no expression was observed in the gill and kidney. Mass spectrometry of affinity-purified EbuNP in plasma, heart and brain revealed a 68 amino acid peptide circulating in the blood and stored in the heart, which is cleaved at the typical cleavage signal of a processing enzyme, furin, as observed in mammalian BNP. The C-terminal Gly residue was used for amidation as is the case in eel ANP. The immunoreactive EbuNP was not detected in the brain, suggesting the presence of a different processing form in the brain. These results show that the molecular evolution of the NP family in vertebrates is more complex than previously thought.

Background & Aims: In this study, we investigated the role of leptin and its receptors (Ob-R) in profibrogenic responses in the liver using Zucker (fa/fa) rats, a natural occurring Ob-R-deficient animal. Methods: Male Zucker (fa/fa) rats and their lean (+/?) littermates were given intraperitoneal injections of thioacetamide (TAA) (200 mg/kg body wt, 3 times/wk) for 4-8 weeks, and progression of hepatic fibrosis was evaluated. In vitro transactivation of hepatic stellate cells (HSCs) isolated from Zucker rats was evaluated by Western blotting and immunocytochemistry for @a-smooth muscle actin and type I collagen. Further, a long-form Ob-R (Ob-Rb) in sinusoidal endothelial cells (SECs) and Kupffer cells was identified by reverse-transcription polymerase chain reaction. Moreover, transforming growth factor (TGF)-@b1. messenger RNA in LSE cells, a human SEC-derived cell line, was measured by Northern blotting. Results: Although the normal liver does not produce leptin, activated HSCs produced leptin in vivo during fibrogenesis caused by TAA. In Zucker rats, TAA-induced hepatic fibrosis was prevented almost completely, whereas induction of TGF-@b1 and activation of HSCs were abolished. It is less likely, however, that leptin plays an essential role in the activation of HSCs as a strong autocrine regulator, because HSCs isolated from Zucker rats undergo normal transactivation process in vitro. In contrast, SECs and Kupffer cells contain Ob-Rb, through which leptin up-regulates the expression of matrix remodeling genes including TGF-@b1. Conclusions: Collectively, these findings indicated that leptin and its functional receptors (Ob-Rb) play a pivotal role in profibrogenic responses in the liver.

OBJECTIVE: Adult onset type II citrullinemia is an inherited disorder of amino acid metabolism caused by a deficiency of liver specific argininosuccinate synthetase activity. Most of the patients with this disease were reported in Japan and therefore, this disease has not been well recognised outside this country. The detailed clinical pictures of the patients with type II citrullinaemia are reported and their outcomes after liver transplantation referred to. METHODS: Ten patients with this disease were evaluated. Seven of them underwent liver transplants using a graft obtained from a healthy family member. RESULTS: There were six men and four women; the age of onset of encephalopathy ranged from 17 to 51 years. The initial symptom in nine patients was sudden onset disturbance of consciousness, and one patient had long been regarded as having a chronic progressive psychotic illness. High concentrations of plasma citrulline and ammonia were commonly seen on admission. Although brain CT or MRI lacked any consistent findings, the EEG was abnormal in all patients, showing diffuse slow waves. Additionally, in five patients chronic pancreatitis preceded the onset of encephalopathy. After liver transplantation the metabolic abnormalities, including abnormal plasma concentrations of citrulline and ammonia, were immediately corrected and all neuropsychic symptoms soon disappeared, except for impaired cognitive function in one patient. Six out of these seven patients returned to their previous social lives, including work. CONCLUSIONS: The clinical concept of adult onset type II citrullinaemia coincides well with the range of hepatic encephalopathy, and liver transplantation is a very promising therapeutic approach.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Kinya Kuriyama. The presentations were (1) Modulation of neuroreceptors and ion channels by alcohol, by T. Narahashi; (2) Inhibition by ethanol of NMDA and AMPA receptor‐channels, by P. Illes, K. Wirkner, W. Fischer, K. Mühlberg, P. Scheibler, and C. Allgaier; (3) Effects of ethanol on metabotropic glutamate receptors, by K. Minami; (4) Acute alcohol actions on the 5‐HT3 ligand‐gated ion channel, by D. Lovinger; (5) Inhibition of NMDA receptors by MK801 attenuates ethanol‐induced taurine release from the hippocampus, by F. Lallemand, R.J. Ward, and P. DeWitte; and (6) Effect of ethanol on voltage‐operated Ca2+channels in hepatic stellate cells, by T. Itatsu, Y. Takei, H. Oide, M. Hirose, X. E. Wang, S. Watanabe, M. Tateyama, R. Ochi, and N. Sato.

A hospital-acquired outbreak with febrile illness and/or rash occurred in our neonatal special care nursery (SCN) from September 1995 to September 1996. A total of 23 infants developed symptoms. We could not detect the etiological agents by routine virus isolation. In a retrospective study, however, enterovirus RNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) from four out of six cerebrospinal fluid (CSF) samples and from two of 12 sera. Thus six out of 16 patients from whom samples were obtained were diagnosed retrospectively as having enterovirus infection. Furthermore, we detected the enterovirus genome from four of 20 serum samples obtained from patients who had other clinical symptoms, and from infants hospitalized without noticeable clinical illness during the same periods. This outbreak was caused by two different enteroviruses, which we assumed were echovirus type 7 (Echo 7) and coxsackievirus B3 (Cox B3), because of the sequence results. We demonstrated the clinical advantage of the analysis of nucleotide sequencing as supportive evidence of transmission.

Experiments were carried out in situ and in vivo to investigate the relationship between natriuretic peptides (NPs) and humoral catecholamine secretion in the American eel (Anguilla rostrata), rainbow trout (Oncorhynchus mykiss) and spiny dogfish (Squalus acanthias). In situ perfusion of the chromaffin tissue of A. rostrata with homologous atrial NP (ANP; 10−9 mol l−1) or ventricular NP (VNP; 10−9 mol l−1), or O. mykiss with either rat ANP (10−9 mol l−1), eel VNP (10−9 mol l−1), or trout VNP (10−9 mol l−1), did not significantly affect basal or carbachol-elicited (10−5 mol kg−1) catecholamine release. Bolus injections of homologous ANP (10−9 mol kg−1) or VNP (10−9 mol kg−1) in A. rostrata in vivo elicited a rapid and prolonged reduction in arterial blood pressure and an increase in heart rate (fH); circulating plasma catecholamine levels were unaffected. In O. mykiss, bolus injections of rat ANP (10−9 mol kg−1) or trout VNP (10−9 mol kg−1) elicited a significant bi-phasic pressor- depressor response and a marked increase in fH. Neither the acute pressor or the longer-term depressor effects of NPs in O. mykiss were associated with any change in circulating plasma catecholamine levels. In S. acanthias, bolus injections of homologous C-type natriuretic peptide (CNP; 10−9 mol kg−1) elicited a bi-phasic pressor-depressor response, an increase in systemic resistance, a decrease in cardiac output and stroke volume, but no change in fH. Plasma noradrenaline levels were elevated 15- fold after CNP injection while circulating adrenaline levels remained unchanged. These results show that NPs of systemic origin do not directly or indirectly affect basal or cholinergically-mediated catecholamine release in A. rostrata and O. mykiss and that the initial pressor response to NP's in trout cannot be attributed to an elevation of circulating catecholamines. Conversely, CNP appears to be a potent secretagogue (direct or indirect) of noradrenaline release in S. acanthias and thus there is likely to be a significant humoral adrenergic component to the cardiovascular effects of NPs in this species.

The renin-angiotensin system (RAS) has been identified recently in elasmobranch fish, and the structure of angiotensin II (ANG II) is unusual ([Asp¹,Pro³,Ile⁵]-ANG II) compared to other vertebrates. Receptors for ANG II have been identified in blood vessels and in a variety of osmoregulatory tissues including the gill, kidney and rectal gland. In addition, there is considerable binding to the interrenal gland and the stimulation of 1α-hydroxycorticosterone production in vitro suggests a physiological role in corticosteroidogenesis. ANG II is a potent vasoconstrictor and this effect does not appear to be mediated by sympathetic activation or catecholamine release. Although the RAS may not be involved in maintaining basal blood pressure, it may be important in situations in which blood pressure is reduced. Understanding of the role of ANG II as an osmoregulatory hormone is only just emerging with putative roles in the control of gill, rectal gland and perhaps, drinking. In addition, the stimulation of corticosteroid secretion may provide another means of controlling osmoregulation. J. Exp. Zool. 284:526–534, 1999. © 1999 Wiley-Liss, Inc.

Angiotensin I (ANG I) was produced from the incubation of lungfish plasma with homologous kidney extracts. The purified peptide was found to have the sequence of H-Asn-Arg-Val-Tyr-Val-His-Pro-Phe-Thr-Leu-OH, which is homologous for the first eight residues with all teleost angiotensins so far sequenced, although lungfish generally possess tetrapod-type hormones. The lungfish decapeptide (ANG I) induced dose-dependent increases in arterial pressure in the rat. The lungfish octapeptide (ANG II) released aldosterone from kidney–adrenal tissuein vitroin a dose-dependent manner and induced dose-dependent increases in arterial pressure of the lungfish. Substitution of asparagine with aspartic acid in the first position (tetrapod-type ANG II) did not alter the blood pressure response significantly, but a second substitution of the valine in the (5)-position with isoleucine (ANG II form found in human and rat) abolished the rise in arterial pressure in lungfish over the same dose range.

Abstract: The contributions of circulating angiotensin II (Ang II) and catecholamines to cardiovascular control in the spiny dogfish were investigated by monitoring the effects of exogenous and endogenous dogfish [Asn1, Pro3, Ile5]-Ang II (dfAng II) on plasma catecholamine levels and blood pressure regulation. Bolus intravenous injections of dfAng II (30–1200 pmol kg−1) elicited dose-dependent increases in plasma adrenaline and noradrenaline concentrations, caudal artery pressure (P CA), and systemic vascular resistance (R S), and a decrease in cardiac output (Q). Similar injections of Ang II in dogfish pre-treated with the α-adrenoceptor antagonist yohimbine (4 mg kg−1) also elicited dose-dependent increases in plasma catecholamine levels yet the cardiovascular effects were abolished. Dogfish treated with yohimbine were hypotensive and had elevated levels of plasma Ang II and catecholamines. Intravenous injection of the smooth muscle relaxant papaverine (10 mg kg−1) elicited a transient decrease in P CA and R S, and increases in plasma Ang II and catecholamine levels. In dogfish first treated with lisinopril (10−4 mol kg−1), an angiotensin converting enzyme inhibitor, papaverine treatment caused a more prolonged and greater decrease in P CA and R S, an attenuated increase in plasma catecholamines, and no change in plasma Ang II. By itself, lisinopril treatment had little effect on P CA, and no effect on R S, plasma Ang II or catecholamines. In yohimbine-treated dogfish, papaverine treatment elicited marked decreases in P CA, R S, and Q, and increases in plasma Ang II and catecholamines. Among the three papaverine treatments, there was a positive linear relationship between plasma Ang II and catecholamine concentrations, and the cardiovascular and hormonal changes were most pronounced in the yohimbine + papaverine treatment. Therefore, under resting normotensive conditions, while Ang II does not appear to be involved in cardiovascular control, catecholamines play an important role. However, during a hypotensive stress elicited by vascular smooth muscle relaxation, Ang II indirectly contributes to cardiovascular control by dose-dependently stimulating catecholamine release.

The individual contributions of, and potential interactions between, the renin-angiotensin system (RAS) and the humoral adrenergic stress response to blood pressure regulation were examined in rainbow trout. Intravenous injection of the smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and significant increases in plasma angiotensin II (Ang II) and catecholamine concentrations. Blockade of alpha-adrenoceptors before papaverine treatment prevented PDA and RS recovery, had no effect on the increase in plasma catecholamines, and resulted in greater plasma Ang II concentrations. Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4) mol/kg), before papaverine treatment attenuated the increases in the plasma concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%, respectively and also prevented PDA and RS recovery. By itself, lisinopril treatment caused a gradual and sustained decrease in PDA and RS, and reductions in basal plasma Ang II and adrenaline concentrations. Bolus injection of a catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in the lisinopril+papaverine-treated trout, to supplement their circulating catecholamine concentrations and mimic those observed in fish treated only with papaverine, resulted in a temporary recovery in PDA and RS. These results indicate that the RAS and the acute humoral adrenergic response are both recruited during an acute hypotensive stress, and have important roles in the compensatory response to hypotension in rainbow trout. However, whereas the contribution of the RAS to PDA recovery is largely indirect and relies on an Ang II-mediated secretion of catecholamines, the contribution from the adrenergic system is direct and relies at least in part on plasma catecholamines.

Studies were undertaken to determine whether leukemia and lymphoma cells would be lysed by autologous and allogeneic lymphokine-activated killer (LAK) cells. Peripheral blood mononuclear cells (PBMC) from patients and normal donors were cultured for five days, 2 weeks, and 4 weeks with medium containing 2,500 units of recombinant interleukin 2 (IL-2) per mL, and their cytotoxicity was assayed by a five-hour 51Cr- release test. Of primary tumors isolated from patients with acute nonlymphoblastic leukemia, acute lymphoblastic leukemia, and non- Hodgkin's lymphoma, tumors of 37 out of 40 patients tested were shown to be susceptible to normal donors' LAK, and tumors of 18 of 20 patients tested were shown to be susceptible to autologous LAK. LAK cultured for longer periods showed a tendency to have lower cytotoxicity. LAK had also low, but significant, levels of cytotoxicity for nonmalignant target cells. Because PBMC expanded in IL-2-containing medium consisted mainly of OKT3-positive pan T cells, OKT8-positive suppressor/cytotoxic cells, and Leu-11-positive natural killer (NK) cells, and treatment with OKT3 and Leu-11 monoclonal antibodies (mAb) reduced LAK activity for autologous and allogeneic tumor cells, both T and NK cells appeared to be effector cells for LAK activity. Mechanisms of target-cell recognition in the LAK system seem to be different from those in alloreactive cytotoxic T lymphocytes (CTL) based on the results that, while cytotoxicity of alloreactive CTL was inhibited by the treatment of effector cells with mAb, OKT3, and OKT8, and by the treatment of target cells with a mAb that reacts with HLA class I antigen, LAK activity was not inhibited by the above treatment. When chromosomes of IL-2-expanded PBMC in nine patients and two normal individuals were analyzed, PBMC from one patient showed chromosomes of clonal abnormalities, and PBMC from five donors showed those of nonclonal abnormalities.

The interaction between homologous dogfish angiotensin II ([Asn1, Pro3, Ile5]-AngII) and catecholamines was examined using blood pressure bioassay. Both noradrenaline and [Asn1, Pro3, Ile5]-Ang II elicited a pressor response. Pre-treatment with phentolamine (1 mg kg-1) completely abolished the noradrenaline pressor response but did not alter the magnitude of the [Asn1, Pro3, Ile5]-Ang II pressor response although there was an initial delay in the response to [Asn1, Pro3, Ile5]-Ang II. These results indicate that the Ang II-induced pressor response is a direct Ang II-mediated vascular response in elasmobranchs.

Electrophysiological studies in vitro demonstrated the significant inhibition by natriuretic peptides (NP) of short-circuit current across the eel intestine, an important osmoregulatory organ. Inhibitory potencies of several members of the NP family were assessed by voltage-clamp determination of net transepithelial salt absorption measured as the short-circuit current Iscacross the intestine of the freshwater-adapted (FW) and seawater-adapted (SW) Japanese eel (Anguilla japonica); the order of potency of synthetic eel peptides was: amidated atrial natriuretic peptide (ANP-NH2) > ventricular natriuretic peptide (VNP) > atrial natriuretic peptide (ANP) >> C-type natriuretic peptide (CNP). Neither the order of potency nor the absolute potencies were effected by salinity adaptation. The observed potency sequence suggests that inhibition of intestinal absorption is mediated by A-type guanylyl cyclase-coupled NP receptors. The relatively low sensitivity of the intestinal response to NP compared with circulating NP concentrations suggests a role for intestinal regulation by NP which is independent of systemic delivery from cardiac sources. A novel model, incorporating the known immunohistochemical localization of NP-ergic cells and processes in the epithelial layer of the intestine and the dissipation of the Na+electrochemical gradient along the alimentary tract, is developed in which local secretion of NP (in response to a bolus of food) inhibits salt absorption across the intestine regionally in favor of increased nutrient absorption.