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Eighteen Swedish patients with familial amyloidotic polyneuropathy were tested for the met30 mutation of the transthyretin (TTR) (prealbumin) gene by RFLP analysis of genomic DNA using the restriction enzyme NsiI. The results confirmed previous findings that the Swedish variant of familial polyneuropathy has the same valine by methionine substitution at position 30, as seen in patients with FAP from Japan, Portugal or patients of Swedish descent from USA. However, two of the patients were homozygous, totally lacking the wild type allele. Measurable serum values for the variant transthyretin (TTR) was detected with a RIA-method in all the 18 Swedish FAP patients studied with a mean concentration of 12.1 +/- 5.1 (SD) mg/100 ml, (11.0 +/- 4.1 when the two homozygotes were excluded). In 45 Japanese patients the mean was 9.2 +/- 2.7 mg/100 ml. The variant TTR was not detected in the healthy controls. The value for the variant TTR was nearly twice that high in the two homozygous patients, 21.14 and 21.16 mg/100 ml, respectively. There was no correlation between the serum levels of variant TTR and the duration of disease or levels of serum albumin in the FAP-patients.

BackgroundStudies of patients with anorexia nervosa (AN) have shown that they do not perform well in set-shifting tasks but little is known about the neurobiological correlates of this aspect of executive function. The aim of this study was to measure serum brain-derived neurotrophic factor (BDNF) and to establish whether set-shifting difficulties are present in people with current AN and in those recovered from AN, and whether serum BDNF concentrations are correlated with set-shifting ability.MethodSerum BDNF concentrations were measured in 29 women with current AN (AN group), 18 women who had recovered from AN (ANRec group) and 28 age-matched healthy controls (HC group). Set-shifting was measured using the Wisconsin Card Sorting Test (WCST). Eating-related psychopathology and depressive, anxiety and obsessive–compulsive symptomatology were evaluated using the Eating Disorder Examination Questionnaire (EDEQ), the Hospital Anxiety and Depression Scale (HADS), and the Maudsley Obsessive–Compulsive Inventory (MOCI) respectively.ResultsSerum BDNF concentrations (mean±s.d.) were significantly lower in the AN group (11.7±4.9 ng/ml) compared to the HC group (15.1±5.5 ng/ml,p=0.04) and also compared to the ANRec group (17.6±4.8 ng/ml,p=0.001). The AN group made significantly more errors (total and perseverative) in the WCST relative to the HC group. There was no significant correlation between serum BDNF concentrations and performance on the WCST.ConclusionsSerum BDNF may be a biological marker for eating-related psychopathology and of recovery in AN. Longitudinal studies are needed to explore possible associations between serum BDNF concentrations, illness and recovery and neuropsychological traits.

We previously demonstrated that 4.7 kDa and 4.4 kDa peptides are useful in diagnosing acute rejection in renal transplant recipients. The aim of this study was to characterize these polypeptides and assess their potential as biomarkers. The polypeptides were identified as human beta-Defensin-1 (4.7 kDa) and alpha-1-antichymotrypsin (4.4 kDa), by tandem mass spectrometry and ProteinChip immunoassay. The urinary abundance of both polypeptides, assessed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), revealed a reduction in beta-Defensin-1 while alpha-1-antichymotrypsin increased in patients with rejection (p < 0.05) compared with clinically stable transplants. The area under the curve (AUC) for the receiver operator characteristic (ROC) curve for the diagnosis of rejection for the ratio of both peptides combined was 0.912. Longitudinal analysis confirmed a reduction in beta-Defensin-1 with a reciprocal increase in alpha-1-antichymotrypsin as rejection developed. The difference in urinary beta-Defensin-1 levels quantified by radioimmunoassay was 176.8 +/- 122.3 pg/mL in stable patients compared with 83.2 +/- 52.2 pg/mL in patients with acute rejection, with an ROC AUC of 0.749 (p < 0.01). Immunohistochemistry (IHC) confirmed reduced beta-Defensin-1 expression in the renal parenchyma of patients experiencing acute rejection. In conclusion, the ratio of beta-Defensin-1 and alpha-1-antichymotrypsin excretion in the urine is a novel, potentially useful candidate biomarkers of acute rejection.

Human β-defensins (hBDs) are the most abundant antimicrobial peptides in epithelial cells, and function in the host immune system. Respiratory epithelial cells express hBDs to inhibit bacterial proliferation during respiratory tract infections. The aim of this study was to investigate the release of hBDs into the respiratory tract and their benefit as a host defence system in chronic Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1–hBD-4) were measured in the bronchial epithelial lining fluid (ELF) of nine patients with chronic lower respiratory tract infection caused by P. aeruginosa. Eight patients with idiopathic pulmonary fibrosis and eight volunteers free of pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic microsampling and hBD levels were measured by radioimmunoassays. The antimicrobial effects of hBDs were studied individually and in combination using an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD-3 tended to be higher in patients with chronic lower respiratory tract infection than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of nine patients, respectively, but the hBD levels in controls were all below the limits of detection. All patients with infection caused by mucoid P. aeruginosa had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are pathophysiologically important in infections caused by mucoid strains of P. aeruginosa.

The growth of mould spores of Penicillium sp. and Cladosporium sp. inoculated in a commercial mineral water product was studied. The strains had been isolated as fungal foreign bodies in commercial mineral waters. In product A, which was not originally sterilized and was contaminated with psychrophilic bacteria, the inoculated mould spores of the strains did not grow; no increases in viable colony counts or β-glucans concentration in the samples were observed during storage. In a sterilized product A, inoculated spores of the strains grew into visible foreign bodies. The viable colony counts and the β-glucans concentration in the samples increased during storage. These results showed that in a sterilized mineral water product, mould spores could grow into visible foreign bodies.

The ability of an extracellular lipase from Pseudomonas aeruginosa KKA-5 to commence hydrolysis of castor oil in the presence of various metal chlorides, was investigated. Apart from CaCl2 (commonly used for castor oil hydrolysis), AlCl3 (group IIIB), CrCl3 (group VIA) and MgCl2 (group IIA) displayed enhanced hydrolysis capability. Specifically, our statistics show that with respect to time, when Cr3+ was used, hydrolysis of castor oil was four times faster than that of calcium, and 1.6 times faster with regards to Al3+. The chlorides of group VIII and alkali metals had no effect on hydrolysis. Group IV metal chlorides did not enhance lipase activity and inhibited castor oil hydrolysis. The effect of metal ions from other groups on lipase activity is also reported.

The spin relaxation timeT 1 for short-lived beta emitters13O and23Mg implanted in Pt have been measured for the first time;T 1T13O) = 2.90 ±0.65 Ks andT 1 T(23Mg) = 1665 ±140 Ks. The Knight shift for13O in Pt was measured at 300 K to beK(13O) = +(4.23 ±0.14) × 10−3. In the case of13O, the Knight shift is unusually large and the relaxation time is unusually fast compared with other interstitial impurities in Pt. A KKR band-structure calculation reproduces the present large Knight shift fairly well.

Human neutrophil peptides (HNPs) 1, 2 and 3, also called defensins, have high antimicrobial activity and are cytotoxic to both normal and transformed human cells. The localization of HNPs 1–3 and their mRNAs in cells of normal human bone marrow and peripheral blood was investigated. Immunoreactivity for HNPs 1–3 appeared in the promyelocyte stage and increased with the maturation of the neutrophil series. HNPs 1–3 were absent from such mononuclear phagocyte systems as peripheral monocytes, alveolar macrophages, and Kupffer cells in the liver. HNP 1–3 mRNAs were detected in bone marrow cells by Northern blot analysis and in peripheral leukocytes by the reverse transcription-polymerase chain reaction (RT-PCR). HNPs 1–3 are restricted to cells of neutrophil lineage and seem to function as microbicidal agents in the neutrophil-mediated defense system.

Peripherally secreted arginine vasopressin (AVP) plays a role in controlling body fluid homeostasis, and central endogenous AVP acts as a neurotransmitter or neuromodulator. The limbic system, which appears to exert an inhibitory effect on the endocrine hypothalamus, is also innervated by fibres that contain AVP. We examined whether central endogenous AVP is also involved in the control of body fluid homeostasis. To explore this possibility, we examined neuronal activity in the paraventricular nucleus of the hypothalamus (PVN), periventricular parts of the PVN and limbic brain areas, as well as AVP mRNA expression in the PVN and the peripheral secretion of AVP after central salt-loading in rats that had been pretreated i.c.v. with the AVP V(1) receptor antagonist OPC-21268. Neuronal activity in the PVN evaluated in terms of Fos-like immunoreactivity (FLI), especially in the parvocellular subdivisions, was suppressed. On the other hand, FLI was enhanced in the lateral septum, the bed nucleus of the stria terminalis and the anterior hypothalamic area. Similarly, AVP mRNA expression was enhanced in the magnocellular subnucleus of the PVN, despite the lack of a significant difference in the peripheral AVP level between OPC-21268- and vehicle-pretreated groups. We recorded renal sympathetic nerve activity (RSNA) as sympathetic nerve outflow during central salt-loading. The suppression of RSNA was significantly attenuated by i.c.v. pretreatment with OPC-21268. These results suggest that the suppression of RSNA during central salt-loading might be the result of a decrease in neuronal activity in the parvocellular subdivisions of the PVN via the inhibitory action of central endogenous AVP. The parvocellular and magnocellular neurones in the PVN might show different responses to central salt-loading to maintain body fluid homeostasis as a result of the modulatory role of central endogenous AVP.

A new method was developed for higher-order eigenmode analysis based on the imaginary-distance propagation method. Our method is useful for vector fields and waveguides with absorption losses. Its validity was confirmed by calculating eigenmodes for a simple optical waveguide.

Emission legislation for diesel engines is becoming more stringent over time. While the exhaust gas composition requirements for prior iterations of emission legislation could be met with improvements in the engine's combustion process, the next issue of emission limits may require more rigorous measures. In order to meet severe particulate matter limitations, such as those mandated in Japan's new long-term (2005-) emission regulation and in Euro-4 emission legislation, the use of exhaust gas after-treatment systems seems unavoidable. Many engine builders seem to have selected the Diesel Particulate Filter (DPF) as an integral part of their selected after-treatment strategy. It has been stated that engine lubricants may hurt the durability of such after-treatment systems when oil consumption results in deposit build-up on the DPF walls. This paper describes how a study was performed on the possible impact of engine lubricant composition on DPF plugging.

Variational analysis, the frequency-temperature characteristics, and the equivalent electrical circuit constants of a face-shear-mode quartz crystal resonator supported at ends, formed by an etching method are described. A vibration analysis is performed in which the equations of motion of the resonator, including both the vibrational and supporting portions, are derived using and energy method. A frequency equation is obtained by applying Galerkin's method to solve the resulting partial differential equations and using displacement obtained from experiments on motional inductance. The resonant frequency, frequency-temperature behavior, and electrical characteristics of the resonator are analyzed by utilizing the frequency equation and displacement. The calculated results are shown to be in good agreement with the measured values. >

A novel cut torsional quartz crystal resonator with an absolute value of the second-order temperature coefficient smaller than that of the tuning fork-type flexural quartz crystal resonator, which is designated the TT-cut, is proposed. Its frequency characteristics, frequency temperature behavior, and electrical characteristics are discussed. First in an analysis procedure, an equation of motion is derived from an energy method. By solving the equation of motion under the boundary conditions of free-free bar or clamped-free bar, the frequency equations are derived. From the equation, a relationship between thickness-to-width ratio and cut angles where the first-order temperature coefficient reaches zero is shown. A tuning-fork-type torsional quartz crystal resonator with excellent frequency temperature behavior is theoretically obtained. The analysis results are then compared with the measured values. Both results are found to agree comparatively well. >

A novel shape length extensional mode quartz crystal resonator with a barbell-type vibration bar, which makes it possible to provide lower frequency, is described. Frequency characteristics, frequency temperature behavior, and electrical characteristics of the resonator are theoretically and experimental clarified. A frequency equation is derived by applying a variational principle whereby a vibration analysis for the resonator is performed, taking into account lateral motions and including a vibrational portion and two supporting portions. Frequency characteristics, frequency-temperature behavior, and electrical characteristics are analyzed. The results are found to agree well with the measured values. The resonator is also miniaturized, is shock-resistant, and has a small series resistance in the frequency range of 200 kHz to 500 kHz, because it is incorporated with the vibrational portion and the two supporting portions by a chemical etching process. >

A new shape length extensional mode quartz crystal resonator with a resonant frequency of 500 kHz to 1.536 MHz is proposed. It is especially suitable for a surface mounting. The resonant frequency, the frequency temperature behavior and the electrical characteristics of the new shape resonator, taking lateral motion into account, are analyzed and examined. In the analysis procedure, an equation of motion of the new shape length extensional mode quartz crystal resonator consisting of a vibrational portion and supporting portions is derived from an energy method. From the obtained equation of motion, the frequency equation is easily calculated. The frequency characteristics, the frequency temperature behavior, and the electrical characteristics of the resonator are analyzed and compared with the measured values. It is shown that the results agree well. >

This paper introduces a new approach to the capacitor-commutated converter (CCC) for HVDC. A small-rated three-phase voltage-source PWM converter is connected between a series commutation capacitor and thyristor rectifier through matching transformers. The PWM converter acts as auxiliary commutation-capacitor for the thyristor rectifier while the series capacitor acts as the main commutation capacitor. The capacitance, which is the sum of the small-rated active and series passive capacitors, is variable, so that stable commutation is obtained. In CCCs commutation failure occurs when the AC bus voltage is recovered whereas the proposed combined commutation-capacitor can achieve successful commutation for both rapidly decreasing and increasing AC bus voltages. The basic principle of the proposed active-passive capacitor commutated converter is discussed in detail. Then, constant margin-angle control with a constant firing angle of the thyristor converter is proposed using a function generator block. Digital simulation demonstrates the novelty and effectiveness of the proposed active-passive capacitor commutated converter.

Uroguanylin is a novel natriuretic and diuretic peptide originally isolated from urine.To determine whether uroguanylin has a physiologic role during the perinatal period, uroguanylin levels in umbilical cord plasma obtained at the time of delivery were measured by radioimmunoassay and compared with cord serum osmolality.Mean (+/- SD) cord plasma uroguanylin concentrations (8.8 +/- 2.1 fmol/mL) were higher compared with normal adult values. The extent of maturity, mode of delivery and gender did not appear to influence cord uroguanylin levels. The uroguanylin concentration had a significant positive correlation with cord serum osmolality.These findings support some regulatory role of this peptide in perinatal renal and cardiovascular adaptation.

We measured the levels of beta-defensin 1 and 2 (HBD-1, 2), novel antimicrobial peptides in plasma and in bronchoalveolar lavage fluid (BALF) from patients with with non-tuberculous mycobacterium infection (NTM). Plasma HBD-2 levels in NTM patients before treatment were higher than those in the controls, while the HBD-1 levels were similar to the control levels. High levels of HBD-2, but not of HBD-1, in BALF were also observed in NTM patients. In NTM, a positive correlation was found between HBD-2 levels in BALF and plasma, and also between HBD-2 and IL-1 beta levels in BALF. NTM patients with cavities or ectasia on chest radiography had higher HBD-2 levels in BALF than those without. Plasma HBD-2 levels in NTM patients were markedly decreased after successful treatment, while those of patients with an intractable mycobacterium infection maintained the same high plasma HBD-2 levels as those before treatment. These findings suggest that HBD-2 may participate in the host defense and plasma HBD-2 levels may reflect disease activity in pulmonary NTM.

The hypothalamus is the most important region in the control of food intake and body weight. The ventromedial 'satiety center' and lateral hypothalamic 'feeding center' have been implicated in the regulation of feeding and energy homeostasis by various studies of brain lesions. Orexins(orexin A and orexin B) and melanin-concentrating hormone (MCH), whose intracerebroventricular injections increase food intake, are localized in the lateral hypothalamus and provide diffuse projections throughout the brain. Orexins and MCH neurons have a coextensive distribution, but are not colocalized. Orexins and MCH may affect feeding behavior through distinct neuronal pathways. We here describe the effect of orexins and MCH on feeding behavior from the physiological, neuroanatomical and molecular studies.

To study whether abnormal secretion of islet amyloid polypeptide is involved in the development of insulin resistance and impaired insulin secretion in Type 2 (non-insulin-dependent) diabetes mellitus, we measured islet amyloid polypeptide concentrations in 56 first-degree relatives of Type 2 diabetic subjects and in 10 healthy control subjects. Fasting islet amyloid polypeptide concentrations were similar in control subjects, glucose-tolerant and glucose-intolerant relatives (8 +/- 1, 9 +/- 1 and 11 +/- 2 fmol/ml; p = NS). The area under the islet amyloid polypeptide curve measured during an oral glucose load was larger in glucose-intolerant relatives (115 +/- 13 fmol/ml) compared to glucose tolerant relatives and control subjects (88 +/- 3 and 79 +/- 12 fmol/ml; p less than 0.05). The insulin response during the oral glucose load was inversely correlated with the rate of glucose disposal measured during a euglycaemic hyperinsulinaemic clamp (r = -0.725; p less than 0.01), while no significant correlation was observed between the corresponding values for islet amyloid polypeptide and glucose disposal (r = -0.380; p = NS). Hypersecretion of islet amyloid polypeptide is observed in glucose-intolerant first-degree relatives of patients with Type 2 diabetes. Since these patients are characterized by insulin resistance and abnormal first-phase insulin secretion, the putative role of islet amyloid polypeptide in the development of these abnormalities remains to be established. It is however, unlikely that islet amyloid polypeptide is involved in the development of insulin resistance as insulin-resistant relatives with normal glucose-tolerance showed normal islet amyloid polypeptide concentrations.

Ghrelin, a novel GH-releasing acylated peptide, was recently isolated from rat stomach. It stimulated the release of GH from the anterior pituitary through the GH secretagogue receptor (GHS-R). Ghrelin messenger RNA and the peptide are present in rat stomach, but its cellular source has yet to be determined. Using two different antibodies against the N- and C-terminal regions of rat ghrelin, we identified ghrelin-producing cells in the gastrointestinal tracts of rats and humans by light and electron microscopic immunohistochemistry and in situ hybridization combined with immunohistochemistry. Ghrelin-immunoreactive cells, which are not enterochromaffin-like cells, D cells, or enterochromaffin cells, accounted for about 20% of the endocrine cell population in rat and human oxyntic glands. Rat ghrelin was present in round, compact, electron-dense granules compatible with those of X/A-like cells whose hormonal product and physiological functions have not previously been clarified. The localization, population, and ultrastructural features of ghrelin-producing cells (Gr cells) indicate that they are X/A-like cells. Ghrelin also was found in enteric endocrine cells of rats and humans. Using two RIAs for the N- and C-terminal regions of ghrelin, we determined its content in the rat gastrointestinal tract. Rat ghrelin was present from the stomach to the colon, with the highest content being in the gastric fundus. Messenger RNAs of ghrelin and GHS-R also were found in these organs. Ghrelin probably functions not only in the control of GH secretion, but also in the regulation of diverse processes of the digestive system. Our findings provide clues to additional, as yet undefined, physiological functions of this novel gastrointestinal hormone.

Clinicopathological and genetic features were assessed on 35 Japanese families affected by late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy, FAP TTR Met30) whose siblings were unrelated to endemic Japanese foci. In these patients (50 years or older), the most common initial symptom was paraesthesias in the legs. Autonomic symptoms were generally mild and did not seriously affect daily activities. The male-to-female ratio was extremely high (10.7 : 1). A family history was evident in only 11 out of 35 families, and other patients were apparently sporadic. The rate of penetrance was very low. Symptomatic siblings of familial cases showed a late age of onset, male preponderance and clinical features similar to those of the probands. Asymptomatic carriers, predominantly female, were detected relatively late in life. The geographical distribution of these late-onset, FAP TTR Met30 cases was scattered throughout Japan. In three autopsy cases and 20 sural nerve biopsy specimens, neurons in sympathetic and sensory ganglia were relatively preserved. Amyloid deposition was seen in the peripheral nervous system, particularly in the sympathetic ganglia, dorsal root ganglia and proximal nerve trunks such as sciatic nerve. These abnormalities were milder than those seen in typical early-onset FAP TTR Met30, as observed in two Japanese endemic foci of this disease. While axonal degeneration was prominent in myelinated fibres, resulting in severe fibre loss, unmyelinated fibres were relatively preserved. Our cases of late-onset FAP TTR Met30 showed features distinct from those of typical early-onset FAP TTR Met30 that occurred in the two Japanese endemic foci. Factors responsible for clinicopathological differences between these two forms of FAP TTR Met30 need to be identified.

A highly stable lipase from Pseudomonas aeruginosa KKA-5 was produced by batch cultivation technique employing shake flask and 5 L-bioreactor. The bioreactor was run at different airflow rates. Low airflow rates (1 and 3 L/min), did not lead to effective growth and lipase production. Growth increased by about one order and lipase production increased by about 6 times, at an airflow rate of 5 L/min. Lipase production occurred during decelerated cell growth. A highly stable lipase was produced which retained its activity in the running bioreactor, even after a period of one month. This stable lipase was partially-purified using ammonium sulphate precipitation technique. Castor oil was hydrolyzed using 300U crude and partially-purified lipase, each. Approximately 21-fold, partially-purified lipase could hydrolyze 81% castor oil within a period of 96 hr, where as only 63% hydrolysis was obtained, in 216 hour, when crude lipase was used.

Japanese familial amyloid polyneuropathy (FAP type I) is characterized clinically by autonomic and sensorimotor polyneuropathy. Bulbar palsy or lower cranial amyloid neuropathy has not been reported in this disease. We report a 72-year-old man with senile onset FAP type I, who developed bulbar palsy and sensorimotor polyneuropathy without autonomic failures. He noticed dysesthesia and muscle weakness in the feet at the age of 67 years. Neurological examination showed bulbar signs and sensorimotor polyneuropathy, but not autonomic neuropathy. Electromyography showed denervation in the tongue and extremities. Sural nerve biopsy revealed a profound reduction of myelinated fibers. Neuropathological studies indicated axonal degeneration and transthyretin-amyloid deposits in the peripheral nerves and hypoglossal nerves or roots. DNA analysis demonstrated transthyretinMet30 mutation. We provide the novel possibility that bulbar palsy, due to amyloid neuropathy, can occur in FAP type I. Copyright Rapid Science Ltd

Uroguanylin, a member of the guanylin peptide family, acts on guanylyl cyclase C (GC-C) to regulate intestinal and renal fluid and electrolyte transport through the second messenger, cGMP. Using an antiserum raised against synthetic rat uroguanylin, we established an RIA and identified three endogenous molecular forms in the intestine and kidney: a 15-amino acid uroguanylin, an 18-amino acid uroguanylin that is a monobasic processing product, and a 9.4-kDa prouroguanylin. Prouroguanylin is the major molecular form in these two tissues, whereas only 15-amino-acid uroguanylin is present in the urine. Rat uroguanylin is most abundant in the proximal small intestine, its content decreasing toward the colon. Uroguanylin is present immunohistochemically in the endocrine cells in the intestine and stomach, B cells in the pancreatic islets, and tubular epithelial cells in the kidney. Uroguanylin has a widespread tissue distribution and is located in cells that function in an endocrine, paracrine, and/or luminocrine (luminal secretion) fashion. Uroguanylin may have physiological functions other than the regulation of fluid and electrolyte transport in the intestine and kidney.

Guanylin and uroguanylin are novel peptides that are first isolated from rat jejunum and opossum urine, respectively. They bind to and activate guanylyl cyclase-C (GC-C) to regulate intestinal and renal fluid and electrolyte transport through the second messenger, cyclic GMP. Heat-stable enterotoxins produced by pathogenic bacteria have close structural similarities to guanylin and uroguanylin, and they use this mimicry to act on GC-C, causing life-threatening secretory diarrhea. Guanylin primarily is restricted to the intestine, whereas uroguanylin is present in the stomach kidney, lung and pancreas in addition to intestine. Guanylin and uroguanylin in the intestine are secreted into the lumen and blood in response to sodium chloride administration. These peptides will function in salt and water transport in the intestine and kidney by luminocrine and/or endocrine actions. Guanylin peptide family links the intestine with the kidney and could play the physiological roles in the control of water and electrolyte balance.

The usefulness of three-dimensional echocardiography using intravascular ultrasound (3D-IVUS) for the measurement of plaque volume was evaluated by comparing plaque volume derived from 3D-IVUS with that directly measured in 10 autopsied iliac or femoral plaque models (5-15 mm long). Using IVUS (3.5 F, 30 MHz), sequential cross-sectional images for three-dimensional datasets were acquired with a motorized catheter pullback device connected to the three-dimensional reconstruction system. Three-dimensional reconstruction was performed from the sum of the two-dimensional cross-sectional views. Plaque volumes were calculated using a summation of disks algorithm based on the reconstructed multiple short-axis cross-sections from the three-dimensional data. Three-dimensional IVUS demonstrated a good correlation with direct measurement of plaque volume (y = 0.71x + 0.001, r = 0.80, SEE = 0.003 ml), so is useful for the measurement of plaque volumes in the experimental models.

Guanylin, a 15-amino acid peptide, activates intestinal guanylate cyclase C receptor, thereby regulating intestinal fluid and electrolyte transport through the second messenger, cyclic GMP. To examine the role of the kidney in guanylin metabolism, we used a radioimmunoassay (RIA) to measure plasma concentrations of guanylin in 3 groups; normal individuals, patients who had renal disorders with normal or elevated serum creatinine levels (0.4Cre11.9 mg/dl), and patients who received hemodialysis (HD). The plasma concentration of immunoreactive guanylin in the normal individuals was 32.3 +/- 4.8 fmol/ml. The concentrations in 32 non-HD patients were correlated with their serum creatinine concentrations (r = 0.81, p0.0001). In 16 HD patients the plasma concentrations of immunoreactive guanylin before the start of HD were correlated with their dialysis duration (r = 0.63, p0.01). The plasma levels of immunoreactive guanylin in HD patients for whom EVAL membranes were used decreased one hour after the start of HD as compared with the prior levels. The plasma levels in HD patients for whom PC membranes were used showed no change. Ten kilodalton guanylin is the main component of guanylin molecules in the plasma and hemofiltrates of HD patients. These findings suggest that the kidney has a major role in the elimination and/or metabolism of guanylin. Uroguanylin, a member of the guanylin family that was recently isolated from human urine, also acts on the guanylate cyclase C receptor. Further studies of guanylin family peptides should provide a better understanding of the physiological roles of the kidney in the control of water and electrolyte balance.

Purpose: Here we have evaluated the effect of an atherosclerosis-related gene on dyslipidemia with the aim of preventing the onset of atherosclerosis. Methods: We performed medical examination on the inhabitants of Goto city from July 2005 to June 2010 under the Goto city sponsorship, and 3,151 inhabitants, who provided informed consent, agreed to continue participating in the study. We divided the participants into groups as per their age and performed a comparative analysis; we collected and analyzed blood samples to determine the association between single nucleotide polymorphisms (SNPs) of 4 genes (MTHFR, Adiponectin, HDAC4, and CARKL) and lipid (Tchol, LDL, TG, HDL) levels. Results: In case of an SNP in the MTHER gene, Tchol and LDL levels were higher in the CC group (in men aged 65 y) than in the TT group (Tchol: CC vs TT, 197.6±34.0 vs 176.5±36.1; p = 0.0143; LDL: CC vs TT, 117.5±30.8 vs 97.6±30.5; p = 0.0115). TG levels were lower in the CC group (in women aged 65 y or older) than in TT group (CC vs TT, 119.5±60.9 vs 148.0±10.2; p = 0.0096), and HDL levels were higher in the CC group than in the TT group (CC vs TT, 59.4±15.9 vs 55.7±15.5; p = 0.0063). In case of SNP in the Adiponectin gene, TG and LDL levels were higher in the TT group (in men aged 65 y or older) than in the GG/GT group, and HDL levels were lower in the TT group than in the GG/GT group (TG: TT vs GG/GT, 137.6±75.7 vs 107.2±67.8; p = 0.0329; LDL: TT vs GG/GT, 133.7±35.6 vs 111.2±30.78; p = 0.0195; and HDL: TT vs GG/GT, 48.0±10.4 vs 56.1±16.3; p = 0.0390) In case of SNPs in the HDAC4 and CARKL genes, there were no significant differences in the lipid levels between the groups. Conclusions: The results show that healthy life expectancy in elderly individuals can be predicted by analyzing the genes with respect to fat metabolism and determining the SNPS associated with the onset of atherosclerosis.

We measured the levels of defensins, antimicrobial peptides, and cytotoxic peptides in azurophil granules of neutrophils in plasma, and in bronchoalveolar lavage fluid (BALF) from patients with the acute respiratory distress syndrome (ARDS). High levels of plasma defensins were observed in samples from patients with ARDS. Samples of BALF from patients with ARDS also had more neutrophils and higher concentrations of defensins than did samples from healthy volunteers and from patients with idiopathic pulmonary fibrosis or diffuse panbronchiolitis. In addition, the concentration of interleukin (IL)-8 in BALF was higher in patients with ARDS than in other subjects. A significant correlation was found between the concentration of defensins and that of IL-8 in BALF from patients with ARDS. These findings suggest that the lung injury in ARDS is caused by defensins released by neutrophils that accumulate in the lungs.

A 64-year-old man has suffered from intractable diarrhea since January 1990. He noticed numbness and weakness in the distal portion of four extremities in the following several months. His symptoms were gradually progressive. In June 1992, neurological examination revealed mild muscular atrophy and weakness in the proximal and distal portions of four extremities. There were paresthesia and severe impairment of superficial sensations in the lower limbs, lower half of the trunk and upper limbs. All deep tendon reflexes were reduced or absent. Autonomic dysfunctions such as orthostatic hypotension, impotence and diarrhea were evident. On sural nerve biopsy, myelinated fibers showing axonal degeneration were predominantly seen, and densities of both myelinated and unmyelinated fibers were markedly decreased. No amyloid deposits were found in the endoneurium. Amyloid deposition was identified in the gastric mucosa by Congo red staining and immunostaining with anti-transthyretin (TTR) antibody. Edman degradation showed one amino acid substitution of Lys for Glu at position 61 in the TTR-peptides from the serum. Direct DNA sequencing revealed a new point mutation in the 61st codon of TTR gene. The same point mutation of TTR gene was identified in the DNAs from his 67-year-old brother and 63-year-old sister and one of the paternal cousins, a 64-year-old woman, although their clinical symptoms and signs were negative. Clinical features such as late onset of the symptoms and signs and presence of carriers in their sixties in this family are unique and atypical as compared with those of more frequent Val30--Met FAP families. A variant TTR, characterized by a Glu61--Lys substitution (a basic-for-acidic amino acid substitution) found in this family, has not been reported in the literature. In the case of the examination of the patients with autonomic and sensory symptoms and signs of unknown etiology, amyloidotic polyneuropathies, including FAP even in the absence of the family history, should be differentiated. When FAP is highly suspected, the combination of family study and DNA analysis of a possible variant TTR is indispensable for the establishment of the diagnosis.

Familial amyloidosis, Finnish type (FAF), is a gelsolin-related systemic amyloidosis that has an autosomal-dominant inheritance pattern and is clinically characterized by progressive cranial neuropathy, corneal lattice dystrophy and skin changes such as cutis laxa, blepharochalasis, and lichen amyloidosis. A 70-year-old Japanese male proband, who was believed to be originally from Fukuoka Prefecture, showed signs and symptoms characteristic of FAF. In addition, he complained of progressive anhidrosis and heat intolerance during the daytime in summer. On examination, perspiration was absent on the almost entire body surface. Molecular genetic studies showed a G-to-A transversion that resulted in the substitution of asparagine for aspartic acid 187 in the gelsolin gene, a mutation found in most patients with FAF. Skin biopsy revealed marked deposition of amyloid, which was positive with anti-gelsolin antibody staining, around eccrine sweat glands and ducts, and around sebaceous glands, outside the basal lamina; slight to mild deposition around small vessels and small nerve fascicles; and very slight deposition in the perineurium and endoneurium. Morphometric evaluation of the nerve terminals and axons of eccrine sweat glands revealed a significant decrease in the number of nerve terminals per transverse profile of the sweat gland. Compared with controls, nerve terminals were further from the secretory epithelial cell owing to deposition of amyloid outside its basal lamina. The proband's sister had almost identical, although much less severe, clinical signs and symptoms with the same mutation of the gelsolin gene. Autonomic signs and symptoms in FAF are reported to be less frequent and less severe than those in familial amyloid polyneuropathy of Andrade type. Findings in our proband suggest that perspiration may be markedly decreased in FAF owing to marked deposition of amyloid around the eccrine sweat gland which causes degeneration of the nerve terminals and disturbs access of the neurotransmitter to the secretory epithelial cell.

The fenestrated Fontan operation is an interim steps for patients who considered to be at high risk for one step Fontan procedure. We performed total cavopulmonary connection with baffle fenestration in five patients under four year of age (33 month of mean age at operation). All patients previously underwent palliative surgery (Blalock shunt in 3, PA banding in 2). Three patients weighed less than 10 kg. Pulmonary vascular resistance index (PARI) were 2.03 +/- 0.18 U/BSA and exceeded 2 U/SQm in 3 patients. Nakata's indice were ranged from 282 to 644 (mean 394) mm2/BSA. Bidirectional cavopulmonary shunt was considered to be alternative pathway for three patients in staged Fontan strategy. Postoperative hemodynamics were relatively stable in all patients and weaned from mechanical ventilation within 5 days with various arterial oxygen saturation. There was no pleural effusion lasting longer than 1 week. One patient died of ileus caused from congenital malrotation. Follow up catheter examination at 1 year showed 83 to 96% of SaO2 and survived patients were doing well. Fenestrated TCPC can be applied safely in younger patients who are considered to need surgical treatments in staged Fontan strategy. Whether fenestration should be closed has to be wait further studies.

We report a Japanese woman with familial amyloidotic polyneuropathy (FAP) with a transthyretin variant that substituted leucine for valine at position 30. Family history was not informative. She had initially suffered from repeated petechiae in the eyelids at the age of 51. Two years later, dysesthesia in the lower extremities appeared. Distal muscle weakness and sensory disturbance gradually developed. Autonomic dysfunction emerged and vomiting and orthostatic hypotension were marked in the late stage of her illness. Because of renal failure, she died at the age of 54. At autopsy, amyloid deposits were prominent in peripheral nerves including autonomic nerves, heart, blood vessels, gastrointestinal tract, kidneys, and bladder. In the nervous system, we found amyloid deposits in anterior roots, posterior roots, posterior root ganglions, peripheral nerves, and sympathetic ganglions. Cardiac weight was increased (595 g) with conspicuous amyloid deposits in the myocardium. The kidneys showed massive deposition of amyloid in the glomeruli and vascular walls. Amyloid accumulated moderately in tongue, submandibular gland, gallbladder, spleen, and pancreas, and slightly in the thyroid gland, lung, liver, and adrenal gland. No amyloid deposits were seen in the CNS with the exception of perivascular deposits in the choroid plexus.

No conservative therapy for endometrial cancer exists. We therefore evaluated the new balloon laserthermia for such cases.Experimental and clinical study. We examined experimentally porcine kidney and stomach, human resected uterus and clinically on 12 patients with endometrial cancer and two patients with hyperplasia.Temperatures were safely kept at the balloon surface. Laser irradiation should be performed for at least 10-15 min, 65-70 degrees C to produce a suitable degeneration, experimentally. Clinically, necrosis and degeneration to a depth of 4-6 mm was histologically observed. Eight patients with carcinoma and hyperplasia for which laserthermia was effective showed that the surface of cancer was smooth and the depth of invasion was in most cases up to 1/4 of muscle layer.Balloon laserthermia may be effective in early endometrial cancer or precancerous lesions. Its clinical usefulness should be investigated further.

Recent advances in protein chemistry and the molecular biology of amyloid proteins have led to knowledge of the primary etiology of FAP. The protein product of the gene in question was identified, then the chromosomal location and point mutations in the gene were determined. Diagnosis of the disorder now can be made at the protein and DNA levels. Recombinant techniques for producing variant proteins have been established and a transgenic mouse that carries the mutated gene have been produced. Liver transplantation, a curative therapy for FAP, has been used for some patients. Procedures for the diagnosis of TTR-related FAP and the elucidation of TTR abnormality are summarized as follows: TTR-related FAP should be considered when biopsies of abdominal fat, the gingiva, stomach, rectum and sural nerves demonstrate amyloid deposits that are specifically stained by anti-TTR antiserum. Analysis of the TTR gene based on RFLP and single strand conformational polymorphism is useful for detecting the genetic mutations identified so far. Even when no known mutations have been detected, protein sequence analysis of serum TTR and nucleotide sequence analysis of the TTR gene have shown new variant TTRs. These advances in FAP research herald a new era in our investigation of the molecular biology of inherited neuropathy.

Spin polarization of beta‐emitting fragment 23Mg(Iπ=3/2+, T1/2=11.3 s) produced through the projectile fragmentation process in 24Mg+Au, Cu, and Al collisions has been observed at 91 AMeV. General trend in the observed momentum dependence of polarization is reproduced well qualitatively by a simple fragmentation model based on the participant‐spectator picture, for heavy and light targets. However the polarization behavior differs from this model in terms of zero crossing momentum, which become prominent in the case of Cu target, where the polarization is not monotone function of the fragment momentum.

TTF-1 is a homeodomain-containing thyroid transcription factor which activates the genes of thyroid specific protein, thyroglobulin, thyroid peroxidase and thyrotropin receptor. We have cloned the TTF-1 gene from rat liver genomic library, and the exon/intron organization and the structure of the 5' flanking region were determined. The clone contained the 5.2 kbp upstream sequence from translation initiation site, and we found that the gene has a single intron in the coding sequence. We found in the 5' flanking region the TTF-1 binding consensus sequence, CTCAAGC, at -175 to -169, which overlaps the consensus sequence of CAAT box, DNase I foot print analysis has revealed that the region is protected by nuclear extract from thyroid cells but not by the extract from the liver, suggesting that expression of the TTF-1 gene is autoregulated by TTF-1.