Production cross sections of Mo, Nb and Zr radioisotopes from α-induced reaction on natZr.

Cross sections of α-induced reactions on natural zirconium were measured up to 50 MeV using the stacked-foil technique, activation method and high resolution γ-ray spectrometry. The production cross sections of 93m,99Mo, 90g,92m,95g,95m,96Nb and 88,89g,95Zr were determined and compared with other experimental data measured earlier and result of theoretical calculations. The integral thick target yield of 99Mo was deduced from the measured cross section data.

Measurement of activation cross sections of alpha particle induced reactions on iridium up to an energy of 50 MeV.

Cross sections of alpha particle induced nuclear reactions on iridium were investigated using a 51.2-MeV alpha particle beam. The standard stacked-foil target technique and the activation method were applied. The activity of the reaction products was assessed without chemical separation using high resolution gamma-ray spectrometry. Excitation functions for production of gold, platinum and iridium isotopes (196m2Au, 196m,gAu, 195m,gAu, 194Au, 193 m,gAu, 192Au, 191m,gAu, 191Pt, 195mPt, 194gIr, 194mIr, 192gIr, 190gIr and 189Ir) were determined and compared with available earlier measured experimental data and results of theoretical calculations using TALYS code system. Cross section data were reported for the first time for the natIr(α,x)196m2Au, natIr(α,x)196m,gAu, natIr(α,x)191Pt, natIr(α,x)195mPt, natIr(α,x)194gIr, natIr(α,x)194mIr, natIr(α,x)190gIr and natIr(α,x)189Ir processes. A possible production route for 195mPt, the potentially important radionuclide in nuclear medicine, is discussed.

Production cross sections of 169Yb and Tm isotopes in deuteron-induced reactions on 169Tm.

The excitation functions of deuteron-induced reactions on 169Tm were measured using the stacked-foil method and high resolution gamma-ray spectrometry. The production cross sections of a medical radionuclide 169Yb were investigated. The result was compared with the previous experiments and found to be in good agreement. In addition to 169Yb, the production cross sections of Tm isotopes, 170Tm, 168Tm and 167Tm, were measured. These results were compared with the TALYS calculations taken from the TENDL-2015 online data library.

Cross section measurement of alpha particle induced nuclear reactions on natural cadmium up to 52MeV.

Cross sections of alpha particle induced nuclear reactions have been measured on thin natural cadmium targets foils in the energy range from 11 to 51.2MeV. This work was a part of our systematic study on excitation functions of light ion induced nuclear reactions on different target materials. Regarding the cross sections, the alpha induced reactions are not deeply enough investigated. Some of the produced isotopes are of medical interest, others have application in research and industry. The radioisotope 117mSn is a very important theranostic (therapeutic + diagnostic) radioisotope, so special care was taken to the results for that isotope. The well-established stacked foil technique followed by gamma-spectrometry with HPGe gamma spectrometers were used. The target and monitor foils in the stack were commercial high purity metal foils. From the irradiated targets 117mSn, 113Sn, 110Sn, 117m,gIn, 116mIn, 115mIn, 114mIn, 113mIn, 111In, 110m,gIn, 109mIn, 108m,gIn, 115gCd and 111mCd were identified and their excitation functions were derived. The results were compared with the data of the previous measurements from the literature and with the results of the theoretical nuclear reaction model code calculations TALYS 1.8 (TENDL-2015) and EMPIRE 3.2 (Malta). From the cross section curves thick target yields were calculated and compared with the available literature data.

Development of novel treatment with a bioabsorbable esophageal patch for benign esophageal stricture.

Using a large animal model, we examined whether circumferential stricture after esophageal endoscopic submucosal dissection (ESD) can be treated by grafting a bioabsorbable esophageal patch. Circumferential ESD was performed on the thoracic esophagus in pigs (n = 6) to create a stricture, for which one of the following interventions was performed: (1) the stricture site was longitudinally incised, and an artificial esophageal wall (AEW) was grafted after placing a bioabsorbable stent (AEW patch group, n = 3); (2) endoscopic balloon dilation (EBD) was performed every other week after stricture development (EBD group, n = 3). In both groups, esophageal fluoroscopy was performed 8 weeks after the interventions, and the esophagus was excised for histological examination of the patched site. In the AEW patch group, esophageal fluoroscopy revealed favorable passage through the patched site. Histologically, the mucosal epithelium and lamina propria had regenerated as in the normal area. In the EBD group, the circumferential stricture site showed marked thickening, and there were hypertrophic scars associated with epithelial defects on the luminal surface. Histologically, defects of the mucosal epithelium and full-thickness proliferation of connective tissue were observed. AEW patch grafting was suggested to be a potentially novel treatment strategy for post-ESD esophageal circumferential stricture.

Vascular endothelium and atherosclerosis.

Atherosclerosis depends critically on altered behavior of the intrinsic cells of the artery wall, the endothelial cells and smooth muscle cells, and inflammatory leukocytes that join them in the arterial intima during the atherogenic process. The homeostatic properties of the normal endothelium contribute importantly to maintenance of aspects of arterial health including the appropriate regulation of blood flow, a basal anti-inflammatory state, promotion of fibrinolysis while opposing blood coagulation, and control of the balance of cellular proliferation and death. Alterations in these endothelial homeostatic mechanisms contribute critically to atherogenesis, the progression of this disease, and ist complications. Recent advances have highlighted novel molecular mechanisms that regulate the atheroprotective functions of normal endothelial cells that go awry during atherogenesis. Therapeutic strategies that alter the course of atherosclerosis may act by combating endothelial dysfunction.

Surface charge of Plasmodium falciparum merozoites as revealed by atomic force microscopy with surface potential spectroscopy.

Electric charges on the surface of Plasmodium falciparum merozoites and erythrocytes were investigated by atomic force microscopy with surface potential spectroscopy. The apical end of merozoites was positively charged, while the entire erythrocyte surface was negatively charged. Transmission electron microscopy also demonstrated that negatively charged nanogold particles attached to the apical end of merozoites, and cationized ferritin particles attached to the entire surface of the erythrocyte. This indicates that the surface charge at the apical end of the merozoite may play an important role in invasion of the erythrocyte.

Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves.

BACKGROUND: The mechanisms of extracellular matrix changes accompanying myxomatous valvular degeneration are uncertain. METHODS AND RESULTS: To test the hypothesis that valvular interstitial cells mediate extracellular matrix degradation in myxomatous degeneration by excessive secretion of catabolic enzymes, we examined the functional characteristics of valvular interstitial cells in 14 mitral valves removed for myxomatous degeneration from patients with mitral regurgitation and in 11 normal mitral valves obtained at autopsy. Immunohistochemical staining assessed (1) cell phenotype using antibodies to alpha-actin (microfilaments), vimentin and desmin (intermediate filaments), smooth muscle myosin (SM1), and SMemb (a nonmuscle myosin produced by activated mesenchymal cells) and (2) the expression of proteolytic activity using antibodies to collagenases (matrix metalloproteinase [MMP]-1, MMP-13), gelatinases (MMP-2, MMP-9), cysteine endoproteases (cathepsin S and K), and interleukin-1beta, a cytokine that can induce secretion of proteolytic enzymes. Although interstitial cells in normal valves stained positively for vimentin, but not alpha-actin or desmin, cells in myxomatous valves contained both vimentin and alpha-actin or desmin (characteristics of myofibroblasts). Moreover, cells in myxomatous valves strongly expressed SMemb, MMPs, cathepsins, and interleukin-1beta, which were weakly stained in controls. Nevertheless, interstitial cells in both groups strongly expressed procollagen-I mRNA (in situ hybridization), suggesting preserved ability to synthesize collagen in myxomatous valves. CONCLUSIONS: Interstitial cells in myxomatous valves have features of activated myofibroblasts and express excessive levels of catabolic enzymes, without altered levels of interstitial collagen mRNA. We conclude that valvular interstitial cells regulate matrix degradation and remodeling in myxomatous mitral valve degeneration.

Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais.

Adhesion molecules on endothelial cells are known to be important ligands for malaria infected red blood cells (PRBC) [Mol Biochem Parasitol, 76, (1996) 1], and may be involved in the pathogenic process of cerebral malaria (CM) which is the most serious complication of falciparum malaria, through enhancing micro embolism or sequestration in the capillaries of the brain. PECAM-1/CD31 is one of these candidate ligands and is coded by a polymorphic gene. Two hundred and ten Thai malaria patients (43 cerebral, 89 severe and 78 uncomplicated) were analyzed for their genetic polymorphism of CD31 to examine the clinical relationship between the disease and specific genotypes. Four alleles were defined 125 valine (V)-563 asparagine (N); 125V-563 serine (S); 125 leucine (L)-563N; and 125L-563S. We found that the frequency of the 125 V/V 563 N/N genotype was significantly high in CM patients as compared with severe cases without CM (P<0.01, OR=2.92), suggesting that this genotype is one of the risk factors for CM.

Molecular biological markers and micrometastasis in resected non-small-cell lung cancer. Prognostic implications.

OBJECTIVES: Recent advances in molecular biology and genetics have created new diagnostic and treatment possibilities in clinical oncology. We evaluated the usefulness of molecular biological factors in primary tumor and micrometastasis in the bone marrow and pathological negative (pN0) lymph nodes as prognostic parameters in non-small-cell lung cancer (NSCLC) patients. METHODS: Pathological specimens were collected from 129 NSCLC patients to analyze molecular biological markers, including K-ras, p53, Rb, p16, loss of heterozygosity (LOH) at 3p, vascular endothelial growth factor (VEGF), and telomerase activity. Bone marrow samples from 250 NSCLC patients and pN0 lymph nodes from 85 of these patients were collected for micrometastasis detection by immunohistochemistry against cytokeratin. RESULTS: p53 abnormalities and 3p LOH were significantly associated with reduced patient survival in adenocarcinoma, whereas VEGF expression was significantly associated with reduced survival in a squamous cell carcinoma histological subtype by univariate or multivariate analysis. We identified micrometastatic tumor cells in bone marrow of 78 (31.2%) of 250 patients and in pN0 lymph nodes of 26 (30.6%) of 85 patients. Both bone marrow and lymph nodal micrometastases were associated with decreased survival among patients with stage I, however, only lymph nodal micrometastasis had a significant impact on survival. CONCLUSIONS: Molecular biological features of primary tumor and micrometastatic status appear useful in defining groups of patients with a poor prognosis who could benefit from adjuvant systemic treatment.

[Results of surgical treatment for primary lung cancer; time trends of survival and clinicopathologic features].

To assess whether the survival of patients who underwent surgical resections for non-small cell lung cancer (NSCLC) improved, we examined the time trends for survival after operation. A total of 851 consecutive patients with NSCLC who underwent surgical resections between 1979 and 2000 were retrospectively reviewed by 3 groups according to year of the operation: the early period (from 1979 to 1986, n = 138), the middle period (from 1987 to 1993, n = 288), and the late period (from 1994 to 2000, n = 425). There were 606 men and 245 women with a mean age of 65.4 years. The histologic type included 453 adenocarcinoma, 282 squamous cell carcinoma, and 63 large cell carcinoma. The pathologic stage included 203 stage I A, 171 stage I B, 21 stage II A, 117 stage II B, 180 stage III A, 123 stage III B, and 36 stage IV diseases. The mean age at the middle and late periods showed a significant increase compared with the early period. There were no significant histologic differences among the three periods. The ratio of patients with stage I A disease increased significantly at the middle and late periods compared with the early period. The 5-year survival rate of the 851 patients was 43.7%, and the median survival was 44.8 months. The 5-year survival rates at the early, the middle, and the late periods were 33.3%, 44.2%, and 45.8%, respectively, with significant improvement at the middle and late periods compared with the early period. The overall 30-day operative mortality was 2.2% (19/851): 8.7% (12/138) at the early period, 1.4% (4/288) at the middle period, and 0.7% (3/425) at the late period, showing significant decrease during the middle and late periods compared with the early period. The postoperative prognosis of patients with resected NSCLC during the later periods had a better survival, which was caused by an increase in the ratio of patients with stage I A disease, and a decrease in the rates of operative mortality.

Biomechanical strain induces class a scavenger receptor expression in human monocyte/macrophages and THP-1 cells: a potential mechanism of increased atherosclerosis in hypertension.

BACKGROUND: Although hypertension is an important risk factor for the development of atherosclerosis, the mechanisms for this interaction are incompletely described. Previous studies have suggested that biomechanical strain regulates macrophage phenotype. We tested the hypothesis that biomechanical strain can induce expression of the class A scavenger receptor (SRA), an important lipoprotein receptor in atherogenesis. METHODS AND RESULTS: Human monocyte/macrophages or THP-1 cells were cultured in a device that imposes uniform biaxial cyclic 1-Hz strains of 0%, 1%, 2%, or 3%, and SRA expression was analyzed. Mechanical strains induced SRA mRNA (3.5+/-0.6-fold at 3% strain for 48 hours, P<0.01) and SRA protein in THP-1 cells in an amplitude-dependent manner. This induction was accompanied by augmented expression of the class B scavenger receptor CD36 (2.8+/-0.3-fold, P<0.001) but not by increased peroxisome proliferator-activated receptor-gamma expression. To evaluate this effect in vivo, apolipoprotein E(-/-) mice were randomly assigned to receive standard chow, a high-cholesterol diet, or a high-cholesterol diet with hypertension induced by angiotensin II infusion for 8 weeks. Immunohistochemistry revealed that among macrophages in atherosclerotic lesions of the aorta, the proportion of macrophages with SRA expression was highest in hypertensive animals on a high-cholesterol diet (43.9+/-0.7%, versus 12.0+/-2.0% for normotensive animals on a high-cholesterol diet and 4.7+/-4.7% for animals on standard chow; P<0.001). CONCLUSIONS: Biomechanical strain induces SRA expression by monocyte/macrophages, suggesting a novel mechanism for promotion of atherosclerosis in hypertensive patients.

CR1 density polymorphism on erythrocytes of falciparum malaria patients in Thailand.

Complement receptor type 1 (CR1) on erythrocytes shows an inherited numerical polymorphism which correlates with a HindIII-RFLP (restriction fragment length polymorphism) of the CR1 gene in various populations. To investigate the relationship between CR1 density polymorphism and disease severity, we typed 185 Thai patients with acute falciparum malaria (55 severe and 130 uncomplicated) for their genotypes of this polymorphism. The level of expression of erythrocyte CR1 from 42 randomly selected patients was measured by enzyme-linked immunosorbent assay (ELISA). We observed a significantly higher frequency of homozygotes of the CR1 low density allele (LL) among the severe group as compared to the uncomplicated group (P = 0.005). CR1 expression on erythrocytes from patients with the LL genotype was significantly lower than homozygotes with the high density allele (HH) (P < 0.0001) and heterozygotes (HL) (P = 0.013). The results suggest that a genetically-determined low CR1 density on erythrocytes may be a risk factor for developing a more severe form of malaria in Thai subjects.

Host bone-marrow cells are a source of donor intimal smooth- muscle-like cells in murine aortic transplant arteriopathy.

Long-term solid-organ allografts typically develop diffuse arterial intimal lesions (graft arterial disease; GAD), consisting of smooth-muscle cells (SMC), extracellular matrix and admixed mononuclear leukocytes. GAD eventually culminates in vascular stenosis and ischemic graft failure. Although the exact mechanisms are unknown, chronic low-level alloresponses likely induce inflammatory cells and/or dysfunctional vascular wall cells to secrete growth factors that promote SMC intimal recruitment, proliferation and matrix synthesis. Although prior work demonstrated that the endothelium and medial SMCs lining GAD lesions in cardiac allografts are donor-derived, the intimal SMC origin could not be determined. They are generally presumed to originate from the donor media, leading to interventions that target donor medial SMC proliferation, with limited efficacy. However, other reports indicate that allograft vessels may contain host-derived endothelium and SMCs (refs. 8,9). Moreover, subpopulations of bone-marrow and circulating cells can differentiate into endothelium, and implanted synthetic vascular grafts are seeded by host SMCs and endothelium. Here we used murine aortic transplants to formally identify the source of SMCs in GAD lesions. Allografts in beta-galactosidase transgenic recipients showed that intimal SMCs derived almost exclusively from host cells. Bone-marrow transplantation of beta-galactosidase--expressing cells into aortic allograft recipients demonstrated that intimal cells included those of marrow origin. Thus, smooth-muscle--like cells in GAD lesions can originate from circulating bone--marrow-derived precursors.

Antibodies specific for heat shock proteins in human and murine malaria.

Heat shock proteins (HSPs) are immunodominant antigens recognized by the host immune system in various infectious diseases. We analyzed HSP-specific antibodies, including immunoglobulin G (IgG), IgM and IgA, in sera from malaria patients in Thailand by using an enzyme-linked immunosorbent assay. All of the antibodies to HSP90 were remarkably increased in the patients compared with those in controls, while only IgM to HSP70 or IgA to HSP65 was significantly elevated. Further experiments showed that anti-HSP IgG was significantly increased in C57BL/6 mice infected with a non-lethal strain of Plasmodium yoelii, with anti-HSP90 IgG being the most elevated. These results suggest that the antigenic potential of HSP90 is higher than those of HSP70 and HSP65 in malaria infection.

A Plasmodium falciparum protein located in Maurer's clefts underneath knobs and protein localization in association with Rhop-3 and SERA in the intracellular network of infected erythrocytes.

We report on the characterization of monoclonal antibodies against Plasmodium falciparum schizonts, which recognize parasite proteins of 130 kDa and 20 kDa. The 130-kDa protein was released by alkaline sodium carbonate treatment, suggesting that the protein is a peripheral membrane protein, while the 20-kDa protein remained associated with the membranes following alkali treatment, suggesting it may be an integral membrane protein. Both proteins were localized to large cytoplasmic vesicles within the cytoplasm of trophozoite and schizont-infected erythrocytes by immunofluorescence assay and confocal microscopy. Both proteins colocalized with Bodipy-ceramide in trophozoite and immature schizont-infected erythrocytes, but not in segmenters. The 130-kDa protein was localized by immunoelectron microscopy (IEM) to Maurer's clefts underneath knobs in a knobby and cytoadherent (K +/ C+) P. falciparum strain. No IEM reactivity was obtained in a knobless and non-cytoadherent (K-/C-)

Invasive forms of Toxoplasma gondii, Leishmania amazonensis and Trypanosoma cruzi have a positive charge at their contact site with host cells.

We examined the surface charges of invasive forms of Toxoplasma gondii, Leishmania amazonensis, and Trypanosoma cruzi by atomic force microscopy and surface potential spectroscopy. We found that the specific part of the protozoan which makes initial contact with the host cell is positively charged. This indicates that the positive charge at the site of contact facilitates binding of the invasive protozoan to negatively charged host cells.

Modulating effects of mucoregulating drugs on the attachment of Haemophilus influenzae.

Non-typable Haemophilus influenzae (NTHI) is one of the three major pathogens implicated in human respiratory infections. The ability to attach with pharyngeal epithelial cells is an important factor for infection and virulence. In the present study we describe the effects of two mucoregulating drugs, S-carboxymethylcysteine (S-CMC) and ambroxol, on the attachment of NTHI to pharyngeal epithelial cells. There was a significant (P < 0.0001, < 0.001 and <0.01) decrease of attachment (8.8 +/ 2.4, 9.2+/-2.5 and 15.4 +/- 5.7 bactreria/cell) compared with the control (17.5 +/- 2.9, 15.5 +/- 3.1 and 18.8 +/- 6.8 bacteria/cell) after cells were treated wth S-CMC at a dose of 100, 10 and 1 microg/ml. After attachment assay, cells treated with S-CMC (100 microg/ml) showed a significant decrease (P < 0.01) of attached bacteria (3.1 +/- 0.8 bacteria/cell) compared with the control (5.9 +/- 1.8 bacteria/cell). Treatment of cells with ambroxol did not influence bacterial attachment. By scanning electron microscopic observation it was found that NTHI attaches to the surface elevations (microplicae) of human pharyngeal epithelial cells. Atomic force microscopic observation revealed that the surface potential of microplicae decreased significantly in cells treated with S-CMC compared with the untreated control cells. As bacteria with negative surface charge attach to the positively charged domain, i.e. microplicae of human pharyngeal epithelial cells, this study suggests that the decrease of attachment of NTHI with epithelial cells after treatment with S-CMC was possibly due to the decrease of surface charge. This study suggests that S-CMC decreases the episodes of respiratory infections in patients with respiratory diseases both by inhibiting the attachment of bacteria to the upper respiratory tract, and by detaching the adherent one.