SIDE-TO-SIDE MESOCAVAL SHUNT IN PORTAL HYPERTENSION

Eighty-five consecutive patients underwent sideto.side mesocaval shunt with a success rate of 98.8'7。and 30day hospital mortality of 2.5"/o. Of 80 casesfollowed up for 3 months t0 8 years, 8 died, 3 hadencephalopathy, 5 rebleeding, 2 ascites and 3 lowerleg edema. A long history of hepatitis and liverfunction impairment were common features of dyingpatients. Rebleeding rate was 8.7'70. Liver functionplayed an important role in the determination of thetherapeutic effect.     

CLINICOPATHOLOGICAL CONFERENCE A 51-YEAR-OLD MAN WITH PALPITAT10N, SHORT BREATH, CYANOSIS AND SUFFOCATION

A 51-year-old man was admitted to our hospital on January 23, 1985 because of pal- pitation and short breath for 40 years. He was well until 7 years of age. Then he devel- oped symptoms ofpalpitation and shortbreath with cyanosisafter exercises. Relief of the symptoms would be achieved by squat- ting for a while or taking a few minutes' rest. Later, his growth was retarded. In 1960 he developed clubbing fingers. In 1965 when hospitalized for tonsillectomy, he was sus- pected of having "congenital heart disease" with ventricular septal defect, stenosis of the pulmonary artery and Eisenmengeris syndrome in question. In 1966, cardiac catheterization was performed, showing that the partial pressure of blood oxygen was l.85 vol%, higher in the right ventricle than in the left auricle. This means there exists a left to right shunt and the magnitude of shunt is 24.0% of the pulmonary circulation. The blood oxygen saturation in the f'emoral artery is a little bit low (93.5%). The hemoglubin concentration is (180g/l). Bilateral shunt could not be excluded.Since August 1969, he began to be very often troubled by nocturnal dyspnea, cough and chest distress. These symptoms could be abated by the treatment of aminophytlline. In 1976, ultrason- ocardiography revealed ventricular septal de- fect and aortic insufficiency. In May 1984. he had high fever for several days and was sus- pected of having "bacterial endocarditisu. The fever subsided with antibiotic therapy for a few db.ys. Twenty days before this hosptalization he had chest distress, short breath, palpitation, cyanosis, nocturnal dyspnea and paroxysmal precordial pain af- ter getting cold.     

TREATMENT OF HYALINEMEMBRANE DISEASE BYHUMAN AMNIOTIC FLUIDSURFACTANT

A case of hyaline membrane disease was treated successfully with pulmonary surfactant (PS) isolated from human amniotic fluid. Dosage was 150 mg phospholipid/kg. The exogenous surfactant was instilled into the airway via a tracheal cannula. Clinical symptoms, PO2 and FiO2 improved evidently 24 hours after administration. L/S ratio and phosphatidylglycerol recovered gradually in aspirates. Lung X-ray film manifested "white lung" before instillation of surfactant and showed a striking improvement 3 days after treatment. The duration of mechanical ventilation was 6 days. During the period of recovery complications of patent ductus arteriosus and bacterial pneumonia developed. However, the patient recovered completely and was discharged 32 days after admission.     

A two-dimensional electrophoresis reference map of human ovary

The ovary plays a central role in oogenesis and gonadal hormone secretion. Proteomic analysis is a valuable approach for gaining an increased understanding of the molecular nature of the ovary. In this work, two-dimensional electrophoresis for protein separation followed by matrix-assisted laser desorption/ionization mass spectrometry and database searches, identified 231 protein spots corresponding to 138 individual proteins that were found in gels representing both the follicular and luteal phases. The data were used to construct a database online (). The identified proteins were functionally classified into seven groups: (1) cell signaling/communication, (2) cell division, (3) gene/protein expression, (4) metabolism, (5) cell structure and motility, (6) cell/organism defense, and (7) unclassified. Among the proteins identified, 47% had not been previously reported in the human ovary. In addition, a number of disease-related proteins were identified in this protein map, including some cancer- and polycystic ovarian syndrome-related proteins. Two proteins with phosphorylation were verified by Western blot analysis. Comparison of protein abundance between follicular and luteal stages produced seven protein spots that had been identified in our database. This study provides a preliminary reference map of normal human ovary that will form a basis for comparative studies on normal and pathological conditions of the human ovary and may serve as a potential tool for clinical diagnosis, therapeutics, and prognosis.Electronic Supplementary Material Supplementary material is available in the online version of this article at L. Wang and Y.-F. Zhu contributed equally to this work     

Epitope mapping and biological function analysis of antibodies produced by immunization of mice with an inactivated Chinese isolate of severe acute respiratory syndrome-associated coronavirus (SARS-CoV)

Inactivated severe acute respiratory syndrome-associated coronavirus (SARS-CoV) has been tested as a candidate vaccine against the re-emergence of SARS. In order to understand the efficacy and safety of this approach, it is important to know the antibody specificities generated with inactivated SARS-CoV. In the current study, a panel of twelve monoclonal antibodies (mAbs) was established by immunizing Balb/c mice with the inactivated BJ01 strain of SARS-CoV isolated from the lung tissue of a SARS-infected Chinese patient. These mAbs could recognize SARS-CoV-infected cells by immunofluorescence analysis (IFA). Seven of them were mapped to the specific segments of recombinant spike (S) protein: six on S1 subunit (aa 12-798) and one on S2 subunit (aa 797-1192). High neutralizing titers against SARS-CoV were detected with two mAbs (1A5 and 2C5) targeting at a subdomain of S protein (aa 310-535), consistent with the previous report that this segment of S protein contains the major neutralizing domain. Some of these S-specific mAbs were able to recognize cleaved products of S protein in SARS-CoV-infected Vero E6 cells. None of the remaining five mAbs could recognize either of the recombinant S, N, M, or E antigens by ELISA. This study demonstrated that the inactivated SARS-CoV was able to preserve the immunogenicity of S protein including its major neutralizing domain. The relative ease with which these mAbs were generated against SARS-CoV virions further supports that subunit vaccination with S constructs may also be able to protect animals and perhaps humans. It is somewhat unexpected that no N-specific mAbs were identified albeit anti-N IgG was easily identified in SARS-CoV-infected patients. The availability of this panel of mAbs also provided potentially useful agents with applications in therapy, diagnosis, and basic research of SARS-CoV.     

Glucocorticoids modulate TGF-beta production

TGF- is thought to play a central role in pulmonary fibrosis inducing fibroblast differentiation and extracellular matrix synthesis. In human lung fibroblasts, it is still unclear how various TGB- isoforms affect TGF- production and whether glucocorticoids, commonly used agents to treat fibrotic lung disease, modulate these processes. To this end, human fetal lung fibroblasts (HFL-1) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TFG-1, -2, and -3. TGF- mRNA was assessed by real time RT-PCR. Smad 2, 3, and 4 and AP-1 complex (c-fos and c-Jun) cellular localization were evaluated by immunostaining. TGF-2 and -3 stimulated TGF-1 production significantly (p < 0.01 relative to control). TGF-1 stimulated TGF-2 production (p < 0.01 relative to control). TGF-3 was undetectable. Glucocorticoids significantly inhibited TGF-1 and -2 production and reduced expression of the upregulated TGF-1 and -2 mRNA induced by exogenous TGF-1, -2 or -3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF--stimulated cells, it was reduced by glucocorticoids. Thus, TGF- isoforms may stimulate production of various TGF- isoforms in the lung. Glucocorticoids then may block TGF- production by modulating mRNA levels and c-Jun.     

Synaptic transmission of chaotic spike trains between primary afferent fiber and spinal dorsal horn neuron in the rat

Primary sensory neurons can generate irregular burst firings in which the existence of significant deterministic behaviors of chaotic dynamics has been proved with nonlinear time series analysis. But how well the deterministic characteristics and neural information of presynaptic chaotic spike trains were transmitted into postsynaptic spike trains is still an open question. Here we investigated the synaptic transmission of chaotic spike trains between primary Adelta afferent fiber and spinal dorsal horn neuron. Two kinds of basic stimulus unit, brief burst and single pulse, were employed by us to comprise chaotic stimulus trains. For time series analysis, we defined "events" as the longest sequences of spikes with all interspike intervals less than or equal to a certain threshold and extracted the interevent intervals (IEIs) from spike trains. Return map analysis of the IEI series showed that the main temporal structure of chaotic input trains could be detected in postsynaptic output trains, especially under brief-burst stimulation. Using correlation dimension and nonlinear prediction methods, we found that synaptic transmission could influence the nonlinear characteristics of chaotic trains, such as fractal dimension and short-term predictability, with greater influence made under single-pulse stimulation. By calculating the mutual information between input and output trains, we found the information carried by presynaptic spike trains could not be completely transmitted at primary afferent synapses, and that brief bursts could more reliably transmit the information carried by chaotic input trains across synapses. These results indicate that although unreliability exists during synaptic transmission, the main deterministic characteristics of chaotic burst trains can be transmitted across primary afferent synapses. Moreover, brief bursts that come from the periphery can more reliably transmit neural information between primary afferent fibers and spinal dorsal horn neurons.     

Skin image segmentation based on energy transformation

In this paper, a new method on extraction of human skin grid centerlines is proposed. The method introduces the physics concepts of kinetic and potential energy into image processing. Regional energy is calculated. Energy transformation is performed to map the pixels from the grayscale space into energy space. Then, the energy image undergoes a morphological filter to remove noises and spurious minima. The amount of filtering can be manually tuned to get a different result. Subsequently, normal curvature of the energy surface is utilized to identify the principal direction and principal curvatures. The ridge centerlines can be detected at the image locations where the principal direction is perpendicular to the normal vector. The experiment shows that this method is an effective one for the purpose of extracting human skin grid.     

Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease

Metal-catalyzed hydroxyl radicals are potent mediators of cellular injury, affecting every category of macromolecule, and are central to the oxidative injury hypothesis of Alzheimer disease (AD) pathogenesis. Studies on redox-competent copper and iron indicate that redox activity in AD resides exclusively within the neuronal cytosol and that chelation with deferoxamine, DTPA, or, more recently, iodochlorhydroxyquin, removes this activity. We have also found that while proteins that accumulate in AD possess metal-binding sites, metal-associated cellular redox activity is primarily dependent on metals associated with nucleic acid, specifically cytoplasmic RNA. These findings indicate aberrations in iron homeostasis that, we suspect, arise primarily from heme, since heme oxygenase-1, an enzyme that catalyzes the conversion of heme to iron and biliverdin, is increased in AD, and mitochondria, since mitochondria turnover, mitochondrial DNA, and cytochrome C oxidative activity are all increased in AD. These findings, as well as studies demonstrating a reduction in microtubule density in AD neurons, suggest that mitochondrial dysfunction, acting in concert with cytoskeletal pathology, serves to increase redox-active heavy metals and initiates a cascade of abnormal events culminating in AD pathology.     

A novel in vivo lecithin-cholesterol acyltransferase (LCAT)-deficient mouse expressing predominantly LpX is associated with spontaneous glomerulopathy

Complete lecithin cholesterol acyltransferase (LCAT) deficiency is a rare genetic cause of extreme reduction in high density lipoproteins and there is a high prevalence of chronic renal dysfunction that may progress to renal failure. Previous in vitro studies suggest the vesicular lipoprotein X (LpX) particles commonly seen in LCAT-deficient plasmas may be causative. To test this hypothesis, we have generated a novel murine model that selectively accumulate LpX in the circulation by cross breeding the sterol regulatory element binding protein (SREBP) 1a transgenic mice (S+) with the LCAT knockout (lcat-/-) mice. Fast protein liquid chromatography fractionation of pooled plasma lipids revealed that virtually all cholesterol is concentrated in the very low density lipoprotein (VLDL)-sized fractions. These fractions are enriched in free cholesterol and phospholipid but extremely poor in triglyceride. Electron microscopy of the d <1.063 g/ml fraction of the S+lcat-/- mice revealed abnormal large vesicular particles, suggestive of LpX. The S+lcat-/- mice developed glomerular lesions spontaneously evident at 6 months with glomerular and tubulointerstitial lipid-deposits. Immunohistochemical staining with RhoA showed marked positive focal staining in glomeruli in the S+lcat-/- mice and undetectable in the S+/lcat+/+ control. By 10 months of age, the kidneys showed progressive glomerular injury including segmental foam cell infiltrates, mesangial expansion, and hyalinosis. Renal abnormalities are very similar to those seen in human LCAT deficiency. We conclude that the selective high-level accumulation of plasma LpX in the S+lcat-/- mice is strongly associated with a spontaneous glomerulopathy, providing in vivo evidence that LpX contributes to the LCAT deficiency-related nephropathy.