Showing papers by "Hokkaido University published in 1988"

Three-dimensional structure of an oncogene protein: catalytic domain of human c-H-ras p21.

Abstract: The crystal structure at 2.7 A resolution of the normal human c-H-ras oncogene protein lacking a flexible carboxyl-terminal 18 residue reveals that the protein consists of a six-stranded beta sheet, four alpha helices, and nine connecting loops. Four loops are involved in interactions with bound guanosine diphosphate: one with the phosphates, another with the ribose, and two with the guanine base. Most of the transforming proteins (in vivo and in vitro) have single amino acid substitutions at one of a few key positions in three of these four loops plus one additional loop. The biological functions of the remaining five loops and other exposed regions are at present unknown. However, one loop corresponds to the binding site for a neutralizing monoclonal antibody and another to a putative "effector region"; mutations in the latter region do not alter guanine nucleotide binding or guanosine triphosphatase activity but they do reduce the transforming activity of activated proteins. The data provide a structural basis for understanding the known biochemical properties of normal as well as activated ras oncogene proteins and indicate additional regions in the molecule that may possibly participate in other cellular functions.

Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 62 patients.

Abstract: These 62 patients with the Kabuki make-up syndrome (KMS) were collected in a collaborative study among 33 institutions and analyzed clinically, cytogenetically, and epidemiologically to delineate the phenotypic spectrum of KMS and to learn about its cause. Among various manifestations observed, most patients had the following five cardinal manifestations: 1) a peculiar face (100%) characterized by eversion of the lower lateral eyelid; arched eyebrows, with sparse or dispersed lateral one-third; a depressed nasal tip; and prominent ears; 2) skeletal anomalies (92%), including brachydactyly V and a deformed spinal column, with or without sagittal cleft vertebrae; 3) dermatoglyphic abnormalities (93%), including increased digital ulnar loop and hypothenar loop patterns, absence of the digital triradius c and/or d, and presence of fingertip pads; 4) mild to moderate mental retardation (92%); and 5) postnatal growth deficiency (83%). Thus the core of the phenotypic spectrum of KMS is rather narrow and clearly defined. Many other inconsistent anomalies were observed. Important among them were early breast development in infant girls (23%), and congenital heart defects (31%), such as a single ventricle with a common atrium, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of aorta, patent ductus arteriosus, aneurysm of aorta, transposition of great vessels, and right bundle branch block. Of the 62 KMS patients, 58 were Japanese, an indication that the syndrome is fairly common in Japan. It was estimated that its prevalence in Japanese newborn infants is 1/32,000. All the KMS cases in this study were sporadic, the sex ratio was even, there was no correlation with birth order, the consanguinity rate among the parents was not high, and no incriminated agent was found that was taken by the mothers during early pregnancy. Three of the 62 patients had a Y chromosome abnormality involving a possible common breakpoint (Yp11.2). This could indicate another possibility, i.e., that the KMS gene is on Yp11.2 and that the disease is pseudoautosomal dominant. These findings are compatible with an autosomal dominant disorder in which every patient represents a fresh mutation. The mutation rate was calculated at 15.6 X 10(6).

Endogenous tumor necrosis factor (cachectin) is essential to host resistance against Listeria monocytogenes infection.

Abstract: During a sublethal murine infection with Listeria monocytogenes cells, tumor necrosis factor (TNF) activity was detectable in neither sera nor spleen homogenates at any stage of the infection when a bioassay with L-929 cells (less than 4 U/ml) was used. However, injecting the mice with an immunoglobulin fraction obtained from a rabbit hyperimmunized with recombinant murine TNF-alpha resulted in acceleration of listeriosis. When 1 mg of anti-TNF antibody was injected per mouse, all the mice died from listeriosis, even though the infectious dose was sublethal for the untreated controls. The antigen-specific elimination of the bacterium from the spleens and livers of anti-TNF antibody-treated mice was delayed, depending on the dose of the antibody injected. Endogenous TNF seemed to be produced early in infection, because suppression of antilisterial resistance was significant when a single injection of anti-TNF antibody was given between day zero and day 2 of infection. The effect of endogenous TNF on antilisterial resistance was due to neither regulation of alpha interferon (IFN-alpha) and IFN-gamma production nor induction of IFN-beta subtype 1 (IFN-beta 1), because anti-TNF antibody treated-mice produced normal levels of IFN-alpha and IFN-gamma in the bloodstream during infection and administration of monoclonal anti-murine IFN-beta 1 antibody had no effect on the development of listeriosis. Alternatively, the listericidal activity of peritoneal macrophages of L. monocytogenes-infected mice could be abrogated by injection of anti-TNF antibody in vivo. These results suggest that the lower level of TNF is produced endogenously in mice that received L. monocytogenes infection and that it plays an essential role in the host defense against L. monocytogenes infection.

Epstein-Barr virus genome-positive T lymphocytes in a boy with chronic active EBV infection associated with Kawasaki-like disease

Abstract: Epstein-Barr virus (EBV), a ubiquitous human herpesvirus and an aetiological agent of infectious mononucleosis, has a unique tropism for B lymphocytes. Clinical and laboratory features of chronic active EBV infections are chronic or persistent infectious mononucleosis-like symptoms and high antibody titre against early antigens (EA). Kawasaki disease (KD), aetiology unknown, is thought to be self-limited immunologically mediated vasculitis. Clinical features of KD are fever, rash, mucositis, lymphadenopathy and coronary artery damage. We report here a child with chronic active EBV infection accompanied by dilatation of coronary arteries. All the EBV-determined nuclear antigen (EBNA)-positive lymphocytes had exclusively CD4 antigen, as revealed by dual staining immunofluorescence analysis. Southern blot hybridization showed that the purified CD4+ cells harboured EBV genome.

Cytoplasmic calcium response to fluid shear stress in cultured vascular endothelial cells.

Abstract: Vascular endothelial cells modulate their structure and functions in response to changes in hemodynamic forces such as fluid shear stress. We have studied how endothelial cells perceive the shearing force generated by blood flow and the substance(s) that may mediate such a response. We identify cytoplasmic-free calcium ion (Ca++), a major component of an internal signaling system, as a mediator of the cellular response to fluid shear stress. Cultured monolayers of bovine aortic endothelial cells loaded with the highly fluorescent Ca++-sensitive dye Fura 2 were exposed to different levels of fluid shear stress in a specially designed flow chamber, and simultaneous changes in fluorescence intensity, reflecting the intracellular-free calcium concentration [( Ca++]i), were monitored by photometric fluorescence microscopy. Application of shear stress to cells by fluid perfusion led to an immediate severalfold increase in fluorescence within 1 min, followed by a rapid decline for about 5 min, and finally a plateau somewhat higher than control levels during the entire period of the stress application. Repeated application of the stress induced similar peak and plateau levels of [Ca++]i but at reduced magnitudes of response. These responses were observed even in Ca++-free medium. Thus, a shear stress transducer might exist in endothelial cells, which perceives the shearing force on the membrane as a stimulus and mediates the signal to increase cytosolic free Ca++.

Relationship between traumatic spinal canal stenosis and neurologic deficits in thoracolumbar burst fractures.

Abstract: Using CT scans of 112 consecutive patients with thoracolumbar burst fractures, we investigated the relationship between traumatic spinal canal stenosis and neurologic deficits. We calculated the stenotic ratios of the area occupied by the retropulsed bony fragments to the estimated area of the original spinal canal. We also examined the shape of the narrowed canal and the disruption of spinal elements. Burst fractures having the following ratios are at significant risk of neurologic involvement: at T11 to T12 with 35% more, at L1 with 45% or more, and at L2 and below with 55% or more.

Noninvasive quantitative analysis of blood oxygenation in rat skeletal muscle.

Abstract: Using the isolated perfused rat hindlimb and the fluorocarbon-transfused rat, we have examined the optical characteristics of the rat skeletal muscle in the near-infrared region. The total contribution of myoglobin and cytochromes to the overall absorbance change was less than 10%. Analyzing transmitted light at 700, 730, and 805 nm, we found linear relationships between the absorbance and the hemoglobin concentrations at hematocrit values from 15 to 50% in the inflowing perfusate. Based on the relationship, we determined the ratio of absorption coefficients at 700, 730, and 805 nm of oxy- and deoxy-hemoglobins of blood in the thigh muscle. The values in thigh muscle were significantly smaller than those in hemoglobin solutions for deoxygenated blood. On the other hand, the values in thigh muscle were larger than those in hemoglobin solutions for oxygenated blood. Solving simultaneous equations by the use of these absorption coefficients, we calculated the changes in the contents of oxy-, deoxy-, and total hemoglobins in the anesthetized rat hindlimb under various conditions. The oxygen saturation of blood determined by our optical method in the thigh muscle was very close to that in the vena cava measured directly with a gas analyzer.

Quantitative analysis of hemoglobin oxygenation state of rat brain in situ by near-infrared spectrophotometry.

Abstract: The light in the near-infrared region (700–900 nm) was illuminated on the rat head, and absorption spectra were measured with the transmitted light under various conditions. The absorbance changes ...

Incoherent turbulence structure in the near wake of a normal plate

Abstract: In this paper experimentally studied characteristics of various frequency components of incoherent velocity fluctuations in the near wake behind a thin normal plate immersed in a uniform flow are described. Measurements were made at a position 8 plate heights downstream of the plate where the wake had a marked periodicity, so that coherent vortices shed from the plate are expected to have a small dispersion in streamwise spacing, transverse location, strength and shape. Shearing stress associated with the incoherent fluctuations is mainly contributed by components with frequencies around half of the vortex-shedding frequency fs on one side of the wake. The ½fs frequency component appears to be caused by the spanwise locations of ribs, which are connected to the coherent vortices, being different from vortex to vortex. A probable spanwise arrangement of the ribs is suggested.

Adaptations to temperate climates and evolution of overwintering strategies in the drosophila melanogaster species group.

Abstract: The Drosophila melanogaster species group is considered to have originated in the tropics and only recently invaded temperate habitats. The temperate species of this group that were studied here may be subdivided into the warm-temperate species (D. lutescens and D. rufa) and the cool-temperate species (species of the auraria complex). The warm-temperate species were more cold-hardy than were their tropical relatives (D. takahashii or D. melanogaster) at the larval and imaginal stages, and the cool-temperate species were more cold-hardy than the warm-temperate species, although only at the imaginal stage. However, these species showed little or no intraspecific variation in cold-hardiness, in spite of great variation in winter temperature within the species' ranges. It is assumed that cold-hardiness is one of the main factors restricting their distributions at high latitudes and that it is the key for evolution of the warm- and cool-temperate species from their subtropical or warm-temperate ancestors. Both warm- and cool-temperate species had photoperiodically controlled reproductive diapause. In the cool-temperate species, the development of cold-hardiness was affected by diapause, but diapause had little or no effect on cold-hardiness in the warm-temperate species. Critical daylengths and the diapause rates varied from species to species according to variation in their overwintering plans and also varied geographically in consequence of their adaptation to local climates. Species showed different responses to temperature in preimaginal and ovarian development. These differences are considered to reflect adaptation to different environmental temperatures.

High susceptibility to hepatocellular carcinoma development in LEC rats with hereditary hepatitis.

Abstract: A remarkably high incidence of hepatocellular carcinomas was observed in long-surviving LEC rats with hereditary hepatitis. Among the 60 LEC rats examined between 12 and 28 months of age from F29, and F30, 55 (92%) developed putative preneoplastic and neoplastic lesions such as hyperplastic foci and nodules, and hepatocellular carcinomas. Of these, hepatocellular carcinomas were observed with a high frequency (46/55; 84%). All rats of advanced age that survived more than 18 months developed hepatocellular carcinomas. These results suggest that the development of liver tumors in LEC rats is an age-associated phenomenon with serial hepatic alterations after the subsidence of acute hepatitis. The long-surviving rats had no normal tissue and showed chronic hepatitis in nontumorous tissues of the liver. Cholangiofibrosis was also found in most rats with hepatic lesions. Metastasis of hepatocellular carcinomas was found in four rats. Histologically, the hepatocellular carcinomas were of a well-differentiated type with a typical trabecular structure. Thus, LEC rats seem to be a promising animal model for studying the pathogenesis of hepatitis and hepatocellular carcinoma.

Minimizing indices of conditional expectations onto a subfactor

Abstract: Pour une paire de facteurs M#74N, soit #7B-E(M,N) l'ensemble de toutes les esperances conditionnelles de M dans N. On caracterise E 0 ∈#7B-E(M,N) dont l'indice est le minimum de {Indice E:E∈#7B-E(M,N,)}. Quand M#74N sont des facteurs II 1 , on etablit la relation entre l'indice E 0 et [M:N]

A new efficient procedure for the estimation of onset times of seismic waves

Abstract: A computationally efficient procedure was developed for the fitting of a locally stationary autoregressive model. The amount of computations is bounded by a function of the data length and the model order only and does not depend on the number of possible arrival times. This facilitates automatic determination of arrival time by an on-line system. The on-line system FUNIMAR (fast univariate case of minimum AIC method of AR model fitting) was developed to implement the procedure. The method was checked by applying it to weak seismic signals from earthquakes which were superimposed with background noises such as traffic noise, electronic hum noise, and heavy microtremor. Experimental results confirm the effectiveness of the method for determining the onset time of P-wave and suggest that an AR model of the fifth order is sufficient to determine the onset time of the wave even if it is buried in considerably heavy noises. It is also shown that the onset time of S-wave can also be successfully determined by the method.

Human HST1 (HSTF1) gene maps to chromosome band 11q13 and coamplifies with the INT2 gene in human cancer.

Abstract: The human HST1 gene, previously designated the hst gene, and now assigned the name HSTF1 for heparin-binding secretory transforming factor in human gene nomenclature, was originally identified as a transforming gene in DNAs from human stomach cancers by transfection assay with mouse NIH 3T3 cells. The amino acid sequence of the product deduced from DNA sequences of the HST1 cDNA and genomic clones had approximately 40% homology to human basic and acidic fibroblast growth factors and mouse Int-2-encoded protein. We have mapped the human HST1 gene to chromosome 11 at band q13.3 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids and in situ hybridization with an HST1 cDNA probe. The HST1 gene was found to be amplified in DNAs obtained from a stomach cancer and a vulvar carcinoma cell line, A431. In all of these samples of DNA, the INT2 gene, previously mapped to human chromosome 11q13, was also amplified to the same degree as the HST1 gene.

Large time behavior of the vorticity of two-dimensional viscous flow and its application to vortex formation

Abstract: We consider the Cauchy problem for the two-dimensional vorticity equation. We show that the solution ω behaves like a constant multiple of the Gauss kernel having the same total vorticity as time tends to infinity. No particular structure of initial data ω0=ω(x, 0) is assumed except the restriction that the Reynolds numberR=∝|ω0|dx/v is small, wherev is the kinematic viscosity. Applying a time-dependent scale transformation, we show a stability of Burgers' vortex, which physically implies formation of a concentrated vortex.

Effects of resource limitation on the physical and reproductive condition of sika deer on Nakanoshima Island, Hokkaido

Abstract: The physical and reproductive condition of introduced sika deer (Cervus nippon yesoensis Heude, 1884) on Nakanoshima Island (5.2 km2) were studied during a 5-year-period.