To what extent do human-altered landscapes retain population connectivity? Historical changes in gene flow of wetland fish Pungitius pungitius.

Understanding how human-altered landscapes affect population connectivity is valuable for conservation planning. Natural connectivity among wetlands, which is maintained by floods, is disappearing owing to farmland expansion. Using genetic data, we assessed historical changes in the population connectivity of the ninespine stickleback within a human-altered wetland system. We predicted that: (i) the contemporary gene flow maintained by the artificial watercourse network may be restricted to a smaller spatial scale compared with the gene flow preceding alteration, and (ii) the contemporary gene flow is dominated by the downstream direction owing to the construction of low-head barriers. We evaluated the potential source population in both timescales. Seventeen studied populations were grouped into four genetically different clusters, and we estimated the migration rates among these clusters. Contemporary migration was restricted to between neighbouring clusters, although a directional change was not detected. Furthermore, we consistently found the same potential source cluster, from past to present, characterized by large amounts of remnant habitats connected by artificial watercourses. These findings highlight that: (i) artificial connectivity can sustain the short-distance connectivity of the ninespine stickleback, which contributes to maintaining the potential source populations; however, (ii) population connectivity throughout the landscape has been prevented by agricultural developments.

Self-awareness of fast eating and its impact on diagnostic components of metabolic syndrome among middle-aged Japanese males and females.

OBJECTIVE: The aim of the present study was to examine the association between subjects with self-awareness of fast eating and diagnostic components of metabolic syndrome in Japanese middle-aged male and female. PATIENTS AND METHODS: Subjects consisted of 3208 males (average age 50.6 years) and 2055 females (average age 50.0 years). Associations between subjects with self-awareness of fast eating and multiple components of metabolic syndrome (waist circumference, body mass index [BMI], blood pressure, and related blood sample tests) were evaluated. RESULTS: Significantly more males (57.7%) acknowledged themselves as "fast eater" than females (46.5%). Self-reported fast eaters showed significantly elevated body weight, BMI, and waist circumference in both genders. However, only male self-reported fast eaters showed high levels of blood pressure, fasting blood glucose, uric acid, and low-density lipoprotein (LDL)-cholesterol. CONCLUSION: Fast eating is associated with diagnostic components of metabolic syndrome. The effect of acknowledging themselves as fast eater presents a higher impact on males than on females in the middle-aged Japanese population. The present study indicates that finding subjects with self-awareness of fast eating may lead to the prevention of developing metabolic syndrome.

Different responses in adult and neonatal hearts to changes in coronary perfusion pressure.

The influence of coronary perfusion pressure on neonatal heart function has not been evaluated. We compared the coronary perfusion pressure-cardiac function relationship between neonatal and adult hearts. Neonatal and adult rabbit hearts were examined. The coronary perfusion pressure was changed in increments of 10 mmHg. Coronary blood flow and left ventricular functions were measured at each coronary perfusion pressure. Autoregulatory capacity for coronary blood flow was quantified by calculating the autoregulation index. In neonatal hearts, left ventricular developed pressure was decreased at high perfusion pressure, whereas in adult hearts left ventricular developed pressure increased at high perfusion pressure. In neonatal hearts, left ventricular enddiastolic pressure was elevated at both low and high perfusion pressure, whereas in adult hearts left ventricular enddiastolic pressure remained constant at all perfusion pressures. Adult hearts exhibited coronary blood flow autoregulation in the perfusion pressure range between 40 and 90 mmHg. In contrast, neonatal hearts did not show autoregulation in any perfusion pressure range. In neonatal hearts, both low and high perfusion pressure caused deterioration in ventricular function attributable to the immaturity of coronary autoregulatory capacity. We conclude that coronary perfusion pressure should be controlled within a narrow range for neonates.

Rational design, discovery, and synthesis of a novel series of potent growth hormone secretagogues.

In the joint experimental and computational efforts reported here to obtain novel chemical entities as growth hormone secretagogues (GHSs), a small database of peptides and non-peptides known to have GHS activity was used to generate and assess a 3D pharmacophore for this activity. This pharmacophore was obtained using a systematic and efficient procedure, "DistComp", developed in our laboratory. The 3D pharmacophore identified was then used to search 3D databases to explore chemical structures that could be novel GHSs. A number of these were chosen for synthesis and assessment of their ability to release growth hormone (GH) from rat pituitary cells. Among the compounds tested, those with a benzothiazepin scaffold were discovered with micromolar activity. To facilitate lead optimization, a second program, a site-dependent fragment QSAR procedure was developed. This program calculates a library of chemical and physical properties of "fragments" or chemical components in a known pharmacophore and determines which, if any, of these properties are important for the observed activity. The combined use of the 3D pharmacophore and the results of the site-dependent fragment QSAR analysis led to the discovery and synthesis of a novel series of potent GHSs, a number of which had nanomolar in vitro activity.

[Spontaneous partial thrombosis of an unruptured peripheral, superior cerebellar artery aneurysm: a case report].

A 52-year-old female suddenly developed headache and dizziness. On admission she complained of gait disturbance with dizziness but cranial nerve palsy could not be detected. CT scan revealed a mild high density lesion in the right ambient cistern and the density of the lesion had become much higher 5 days after admission. MRI revealed a homogeneous iso-intense lesion on T1WI, T2WI 2 days after admission and the lesion had changed to homogeneous high. The lesion was suspected to be a fresh thrombus. Right vertebral angiography showed a part of aneurysm arising from the ambient segment of the right superior cerebellar artery and we diagnosed the lesion as a partially thrombosed superior cerebellar artery aneurysm. About forty cases of peripheral superior cerebellar artery aneurysm have been described in the literature, but cases of spontaneous thrombosis of the aneurysms have been very rare. Spontaneous thrombosis of aneurysms was usually thought to occur in large aneurysms, but the aneurysm in our case was not large. We suspected that in our case spontaneous thrombosis may have been caused by occlusion of the parent artery of the aneurysm.

Molecular characterization of hepatitis C virus genotype 2a from the entire sequences of four isolates.

Genotype 2a hepatitis C virus (HCV) has different characteristics from genotype 1b, such as responsiveness to interferon therapy. Such type-specific characteristics appear to be due to differences in the HCV genome sequence. The complete sequences of genotype 2a HCV genome isolated from four patients with chronic hepatitis C were determined, and nucleotide and deduced amino acid sequences were compared within genotype 2a, as well as between genotype 2a and 1b. Whereas the amino acid sequence similarity of the core region was highest within genotype 1b, the NS3 and NS4B regions of exhibited greater similarity than the core region in genotype 2a. The serine protease and helicase motifs in the NS3 region were well conserved in genotype 2a to the same degree as in genotype 1b. However, the putative secondary structure of 2a isolates was significantly different from that of the 1b isolates. Analysis of amino acid similarity between genotypes 2a and 1b revealed the lowest degree of similarity in the E1 region, followed by the NS2 and NS5A region. Sequences of genotype 2a in the interferon-sensitivity determining region (ISDR) located in the NS5A region had a deletion of four amino acids compared with that of genotype 1b. When the ISDR of the genotype 2a was aligned for maximal similarity, it exhibited similarity of only 52.5-55.0% when compared with that of HCV-J, which belongs to genotype 1b. These findings for the entire sequences of genotype 2a isolates will contribute to virological studies of HCV.

[The early hemorrhage and development of a bacterial aneurysm after a cerebral ischemic attack caused by a septic embolism--a case report].

A 71-year-old female was admitted with the complaints of dysarthria and right hemiparesis. CT scan revealed subarachnoid hemorrhage in the left cerebral sulcus. The first angiography was performed 3 days after the onset and left carotid angiography revealed a small aneurysm arising from the left middle cerebral artery. After 3 weeks of antibiotic therapy, the second angiography showed the aneurysm to be clearly enlarged, so it was resected. The patient complained of marked dysarthria a day after the operation and CT scan revealed a new infarction in the right frontal lobe. The third angiography showed an aneurysm arising from the right middle cerebral artery and the fact that two peripheral arteries of the aneurysm had disappeared 3 weeks after the first operation. The second operation was performed and a bacterial aneurysm was resected. The patient left the hospital without any neurological deficits. Septic embolism is the most important complication of infective endocarditis and it is usually presented with subarachnoid hemorrhage and intracerebral hemorrhage caused by ruptured bacterial aneurysms. In this case the septic embolism occurred two times. At each time cerebral ischemic attacks were presented. The reason why this case presented with ischemic symptoms was suspected to be that embolisms occurred at the trifurcation of the distal middle cerebral arteries. We were able to detect a bacterial aneurysm angiographically 3 days after the ischemic attack and we suspected that a bacterial aneurysm had been able to develop within 3 days after the septic embolism.

[Aspiration and drainage for a gas-producing brain abscess causing delayed bleeding from the abscess capsule--a case report].

A 65-year-old man was admitted with the complaint of gait disturbance. CT scan revealed a low density lesion in the right parietal lobe. MRI was carried out 3 days after admission, the lesion showing low intensity on T1 WI and T2 WI. Gd-DTPA enhanced T1 WI showing abnormal enhancement surround it. CT scan then revealed a gas bubble in the lesion 12 days after admission, so we diagnosed it as gas-producing brain abscess and aspiration, drainage and irrigation with antibiotics were performed. Although, the brain abscess was reduced in size after the operation, the lesion expanded again 2 weeks after the operation. MRI was performed and the lesion showed iso-intensity on T1 WI and high intensity on T2 WI. Emergent aspiration and drainage were performed and uncoagulated old-hematoma-like matter such as chronic subdural hematoma was removed. As significant neovascularization with inflammatory cells had been detected in the capsule of the brain abscess, we suspected that aspiration and drainage surgery for brain abscess may cause delayed bleeding from the capsule of the abscess. We conclude that attention should be drawn to such a complication.

Changes of DNA titer and sequence variance of TT virus in hepatic disorders.

TT virus (TTV) has been reported to occur in association with elevated alanine aminotransferase (ALT) levels in patients with posttransfusion hepatitis of unknown etiology. We examined whether the presence, change of DNA titer, or variation in sequence of this virus is associated with acute or chronic liver dysfunction in Japanese. We detected TTV by polymerase chain reaction (PCR) using primers generated from the conserved region of the TTV genome. Direct DNA sequencing of the original N22 region was used to characterize TTV isolates. We detected TTV DNA in 15 (25%) of 60 patients with liver dysfunction. Variants recovered from infected patients formed four genotypes/subtypes, corresponding to G1a, G1b, G2, and G4. Although TTV DNA titers in patients with G2 and G4 were lower than those with G1, TTV was consistently detected regardless of genotype/subtype. TTV infection continued for at least 1 year after normalization of ALT level in patients with acute liver dysfunction. Changes in DNA titer, substitutions of deduced amino acids, and variety of quasispecies of TTV were detected during the observation period, but no significant fluctuation in ALT level was found. We conclude that persistent infection, changes in DNA titer, and variation in sequence of this novel virus are not significantly related to hepatic disorders.

The effects of deimination of myelin basic protein on structures formed by its interaction with phosphoinositide-containing lipid monolayers.

The recombinant 18.5-kDa charge isoform of murine myelin basic protein (rmMBP) is unmodified posttranslationally and was used to study the effects of deimination, i.e., the conversion of arginyl to citrullinyl residues, on the protein's interactions with itself and with lipids. The unmodified species rmMBP-Cit(0) (i.e., containing no citrullinyl residues) interacted with binary monolayers containing acidic (phosphatidylinositol) and nickel-chelating lipids to form paracrystalline arrays with 4.8-nm spacing. A sample of protein was deiminated to an average of 9 citrullinyl residues per molecule of protein, yielding rmMBP-Cit(9). Under both low- and high-salt conditions, this species formed better-ordered domains than rmMBP-Cit(0), viz., planar crystalline assemblies. Thus, deimination of MBP resulted in a significant alteration of its lipid-organizing and self-interaction properties that might be operative in myelin in vivo, especially in progression of the autoimmune disease multiple sclerosis. Comparisons of amino acid sequences indicated significant similarities of MBP with filaggrin, a protein that is deiminated in another autoimmune disease, rheumatoid arthritis, suggesting that comparable epitopes could be targeted in both pathologies. In contrast, binary lipid monolayers consisting of phosphatidylinositol-4-phosphate (or phosphatidylinositol-4,5-bisphosphate) and a nickel-chelating lipid formed helical tubular vesicular structures, which appeared to be induced and/or stabilized by rmMBP, especially in its deiminated form. Sequence comparisons with other actin- and phosphoinositide-binding proteins (vinculin, ActA, MARCKS) suggested that the carboxyl-terminal segment of MBP could form an amphipathic alpha helix and was the phosphoinositide binding site.

Characterization of a recombinant murine 18.5-kDa myelin basic protein.

A recombinant hexahistidine-tagged 18.5-kDa isoform of murine myelin basic protein has been characterized biochemically and immunogenically, by mass spectrometry, by circular dichroism under various conditions (in aqueous solution, with monosialoganglioside G(M1), and in 89% 2-propanol), and by transmission electron microscopy. The preparations of this protein indicated a high degree of purity and homogeneity, with no significant posttranslational modifications. Circular dichroic spectra showed that this preparation had the same degree of secondary structure as the natural bovine 18.5-kDa isoform of myelin basic protein. Incubation of the recombinant protein with lipid monolayers containing a nickel-chelating lipid resulted in the formation of fibrous assemblies that formed paracrystals of spacings 4.8 nm between fibers and 3-4 nm along them.

[The presence of air in epidural hematoma due to congenital bone defect in the mastoid tegmen--a case report].

Presence of air in acute epidural hematomas has been described by several authors. Although the air trapped in the epidural space is thought to be derived from the air-containing structure, there are some cases in which there is an absence of any demonstrable fracture involving air-containing structure. We report a very rare case of air in an epidural hematoma which was not related to fracture involving air-containing structure. The patient was a 30-year-old man whose left temporal bone was struck during a fall. CT scan revealed acute epidural hematoma with a large amount of air in the epidural space. We found many congenital bone defects in the mastoid tegmen during the operation and suspected that the air had been derived from them. The difference between our case and other cases reported was the amount of the air in epidural space. We suspected that air bubbles were derived from the fracture involving air-containing structure, while a large amount of air could be derived from congenital bone defects in the mastoid tegmen.

A case of probable acute interstitial pneumonia with a dramatic response to pulse corticosteroid administration.

A 38-year-old Japanese male without any significant respiratory risk factors was admitted to our hospital because of an acute onset of fulminant pneumonia refractory to intravenous antibiotics administration and an unexplained creatine kinase elevation. He was intubated and under ventilator support on the second hospital day, but responded dramatically to i.v. pulse methylprednisone treatment. After exclusion of secondary etiologies including collagen diseases, we concluded this case as a probable acute (idiopathic) interstitial pneumonia, or Hamman-Rich syndrome, responding dramatically to the corticosteroid pulse administration.

Analogous structural motifs in myelin basic protein and in MARCKS.

Myelin basic protein (MBP) and myristoylated alanine-rich C-kinase substrate (MARCKS) are similar in terms of having extended conformations regulated by their environment (i.e., solubilised or lipid-associated), N-terminal modifications, a dual nature of interactions with lipids, binding to actin and Ca2+-calmodulin, and being substrates for different kinds of protein kinases. The further sequence similarities of segments of MBP with lipid effector regions of MARCKS, and numerous reports in the literature, support the thesis that some developmental isoform of MBP functions in signal transduction.

Myelin basic protein component C1 in increasing concentrations can elicit fusion, aggregation, and fragmentation of myelin-like membranes.

Myelin basic protein (MBP) is considered to have a primary role in the formation and maintenance of the myelin sheath. Many studies using artificial vesicle systems of simple lipid composition, and generally small size, have shown that MBP can elicit vesicle fusion, aggregation, or even fragmentation under different conditions. Here, we have studied the effects of increasing concentrations of bovine MBP charge isomer C1 (MBP/C1) on large unilamellar vesicles (LUVs) composed of phosphatidylcholine and phosphatidylserine (92:8 molar ratio), or with a lipid composition similar to that of the myelin membrane in vivo (Cyt-LUVs). Using absorbance spectrophotometry, fluorescence resonance energy transfer, dynamic light scattering and transmission electron microscopy, we have shown that vesicle aggregation and some vesicle fusion occurred upon addition of MBP/C1, and as the molar protein-lipid ratio increased. Fragmentation of Cyt-LUVs was observed at very high protein concentrations. These results showed that the phenomena of vesicle fusion, aggregation, and fragmentation can all be observed in one in vitro system, but were dependent on lipid composition and on the relative proportions of protein and lipid.

[Perineural spreading along the trigeminal nerve in a patient with primary intracranial malignant lymphoma: a case report].

We report a rare primary intracranial malignant lymphoma which spread along the trigeminal nerve through the skull base foramen. The patient was a 50-year-old woman, who was diagnosed as having a primary intracranial malignant lymphoma in the right temporal lobe and had undergone an operation and radiation 5 years previously. The tumor was reduced in size and no recurrent tumor could be detected for 5 years. The patient complained of left face swelling and CT scan revealed a large mass in the pterygopalatine fossa. MRI revealed the recurrent tumor in the left Meckel's cave with extension into the cavernous sinus. The tumor extended through the foramen ovale into the pterygopalatine fossa, through the superior orbital fissure into the orbital cavity and through the infraorbital fossa into the face subcutaneously. Biopsy of the subcutaneous tumor was carried out and the pathological diagnosis was malignant lymphoma, B cell type, which was identical with the initial tumor. MRI revealed the enlarged trigeminal nerve and 3D-CT revealed the enlargement of the infraorbital fossa and the foramen ovale. We suspected that primary intracranial malignant lymphoma had recurred in the left Meckel's cave and the tumor had spread along the peripheral three divisions of the trigeminal nerve. Perineural spreading along the trigeminal nerve passing through the skull base in patients with nasopharyngeal carcinoma is not rare, but this rarely occurs in the case of intracranial tumors.

[The stenoses at the terminal portion of the internal carotid artery improved after initiation of antithyroid therapy: a case report].

We reported the case of a 19-year-old female complicated with Basedow disease. She was admitted, complaining of headache and endocrine function tests showed hyperthyroidism. CT scan revealed left intraventricle hemorrhage and angiography revealed the stenoses at the terminal portion of the bilateral internal carotid arteries (ICA) without basal moyamoya vessels. During the angiography, a thyroid crisis occurred and we initiated the antithyroid therapy. Bilateral CAG a month after the onset revealed that the stenoses had improved partially and the stenosis was thought to be vasospasm caused by the intraventricle hemorrhage. But as the collateral circulation had already been established soon after the hemorrhage, we suspected that the stenoses at the terminal portion of the ICA had existed before the intraventricle hemorrhage. Angiography was performed one year after the onset and bilateral CAG revealed that the stenoses at the terminal portion of the ICA had also improved. As some investigators have mentioned that Basedow disease might be associated with the causal genesis of Moyamoya disease, we suspected that Basedow disease might have played an important role in vasospasm after hemorrhage and that the stenoses at the terminal portion of the ICA might have existed before the hemorrhage took place.

Contemplation of age-adjusted standard values of lipid profiles in Japan.

In order to establish the age-adjusted standard values of lipids in both sexes in Japan, we examined the plasma levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride levels in 1262 healthy Japanese subjects (male 616, female 646). LDL-cholesterol levels in women increased significantly in relation to menopause as it rises from 112 mg/dL in 40 year olds to 131.2 mg/dL in 50 year olds. Menopause seems to affect the triglyceride levels as well. These age- and sex-dependent changes should be considered in evaluation of patients' lipid profiles.

Immunological enhancement with a low dose of cyclophosphamide in aged mice.

Aged mice treated with a low dose of cyclophosphamide (CY) showed significantly enhanced immune capacity in cellular proliferation and antibody response. In these mice, total cell numbers were increased both in the thymus and spleen, compared to those in non-treated mice. Treatment with a low dose of CY induced apoptosis of thymocytes in the atrophic thymus of the aged mice, being followed by an increase of proliferation of thymocytes and leading to an increase of thymocytes and splenic T cells. Treatment with a high dose of CY also induced apoptosis in the thymus, but suppressed the proliferative capacity, therefore not leading to an enhancement of immune capacity. In young mice, however, CY suppressed immune capacity regardless of the dose. Thymocytes and splenic T cells of young mice were more susceptible to CY than those of old mice and were decreased in number after the treatment with even a low dose of CY.

[The natural history of a dural arteriovenous fistula associated with sinus thrombosis: a case report].

The patient, a 52-year-old man, complained of vertigo. CT scan revealed right cerebellar infarction and he was admitted to our hospital. MRI revealed a fresh thrombus in the right transverse sinus and angiography revealed the occlusion of the right transverse-sigmoid sinus. He complained of vertigo again and he was re-admitted to our hospital 4 months after the first admission. Angiography revealed a dural arteriovenous fistula (DAVF) of the right transverse-sigmoid sinus fed by the right occipital artery and the right transverse-sigmoid sinus was found to be recanalized. The angiography which was carried out one year after the second admission, revealed also an enlarged DAVF fed by the left occipital artery and the right transverse sinus was occluded again. There are two theories about the pathogenesis of DAVF. One is that it is congenital and the other that it is acquired, but it is still controversial. Our case suggested that sinus thrombosis induced DAVF initially and the DAVF induced sinus thrombosis secondarily. The causal relations between DAVF and sinus thrombosis probably changed inversely over a long term and, when we discuss the pathogenesis of DAVF, we must understand the natural history of DAVF starting from the occurrence of sinus thrombosis.