Activation of murine leukaemia virus under different physiological conditions.

The leukaemic lesions in intact and ovariectomized mice of strain ICRC, induced with 20-methylcholanthrene (20-MCA) in combination with or without hormones were investigated for the presence of mouse leukaemia virus (MuLV) by (i) bioassays and (ii) electron microscopy. The different experimental groups treated with 20-MCA were (i) intact females, (ii) ovariectomized females, (iii) ovariectomized females with pituitary graft, (iv) ovariectomized females with 10 mug oestradiol/day for 30 days and (v) ovariectomized females with 1 mug oestradiol together with 1 mg progesteron/day for 30 days. It was possible to transmit nearly all these experimentally induced leukaemias to syngeneic mice through acellular extracts, compared with very poor transmissibility of spontaneous leukaemias in the ICRC strain, indicating functional activation of viral agents on combined treatment with carcinogen and hormones. Potency of the acellular leukaemic extract from the mice of group (ii) without the ovarian hormones was much weaker than that from mice of the other experimental groups. The leukaemogenic activity of MuLV was enhanced on serial transmission in syngeneic hosts. Leukaemic lesions of ovariectomized mice treated with 20-MCA and oestradiol were also transmissible to the sucklings of allogeneic mice of strain C3H-MTV, C57-BL and Dba-MTV. The cell-free supernatant medium of the cultures of these leukaemic lesions induced leukaemias on back inoculation into syngeneic mice. Electron microscopic studies of lesions induced with carcinogen and oestradiol consistently showed abundant intracytoplasmic type A particles. Numerous intracytoplasmic type A particles as well as some type B particles were found in the leukaemic tissues of ovariectomized females treated with MCA and oestradiol combined with progesterone. Type C particles, characteristic of MuLV were seen in the leukaemic tissues of all other experimental groups. These findings indicate a significant influence of the physiological condition of the host, particularly the hormonal make up, on expression and activity of specific viral agents

Riboflavin carrier protein: a serum and tissue marker for breast carcinoma

We have earlier shown that the estrogen-modulated riboflavin carrier protein (RCP) first isolated from the chicken egg is evolutionarily conserved in mammals and is elaborated by lactating mammary gland as demonstrated with rat mammary epithelial cells in culture and confirmed by isolation of the vitamin carrier from bovine milk. In view of several earlier reports that many milk proteins as well as other estrogen-inducible proteins are up-regulated and secreted into circulation in animal models and in women with neoplastic breast disease, we analyzed serum RCP levels in a double-blind study using a specific radioimmunoassay in pre- and post-menopausal women with clinically diagnosed breast cancer at early and advanced stages of the disease and compared these levels with those in normal age-matched control volunteers. Our data reveal that the serum RCP levels in cycling breast cancer patients are 3- to 4-fold higher (p < 0.01) than those in their normal counterparts. This difference in circulatory RCP levels between cancer patients and their age-matched normal counterparts is further magnified to 9- to 11-fold (p < 0.005) at the post-menopausal stage. In addition, there seems to be a good correlation between rising RCP levels and disease progression, since significantly higher RCP concentrations (p < 0.005) are encountered in patients with advanced metastasizing breast cancer versus those with early disease. Using specific monoclonal antibodies, RCP could be localized immunohistochemically in the cytoplasm of invading neoplastic cells of lobular and ductal carcinomas of the breast, indicating that the malignant cells are probably the source of the elevated serum RCP levels in breast cancer. These findings suggest that measurement of circulatory RCP and the immunohistochemical staining pattern of RCP in biopsy specimens could be exploited as an additional marker in diagnosis/prognosis of breast cancer in women

Intracytoplasmic type A particles from mammary tumours and leukaemias of strain ICRC mice.

The ovarian-hormone-induced leukaemias of strain ICRC mice, with an abundance of intracytoplasmic type A particles in primary as well as transplanted lesions, were used to study morphological, biophysical, immunological and structural characteristics of type A particles. Mammary tumours of strains ICRC and C3H(Jax) were also used as sources for type A particles. The purified virions banded at the density of 1.20 g/ml in 12--60% linear sucrose-density gradient when subjected to spinning at 113,000 g for 4 h. The SDS-polyacrylamide-gel electrophoresis of type A particles from mammary tumours and leukaemias reproducibly resolved at least 8 polypeptides, 2 of these 54,000 and 24,000 dalton proteins, showing variable expression. Type A particles and B particles, despite the fact that each had a distinct polypeptide pattern, showed common antigens with different electrophoretic mobilities. Proteins of 24,000, 18,000 and 12,000 daltons from B particles were found to be antigenically related to those from type A particles. The bioassay studies carried out with purified A particles showed that 2/7 males of strain ICRC and 1/6 females of strain DBA-MTI developed leukaemias, as against none in the controls, when inoculated between the ages of 1-7 days. Spleen tumour and cervical tumour were seen in one female each of strain DBA-MTI

Impact of metal on the DNA photocleavage activity and cytotoxicity of ferrocenyl terpyridine 3d metal complexes

Ferrocenyl terpyridine 3d metal complexes and their analogues, viz. [M(Fc-tpy)2](ClO4)2 (1-4), [Zn(Ph-tpy)2](ClO4)2 (5) and [Zn(Fc-dpa)2]X2 (X = ClO4, 6; PF6, 6a), where M = Fe(II) in 1, Co(II) in 2, Cu(II) in 3 and Zn(II) in 4, Fc-tpy is 4'-ferrocenyl-2,2':6',2''-terpyridine, Ph-tpy is 4'-phenyl-2,2':6',2''-terpyridine and Fc-dpa is ferrocenyl-N,N-dipicolylmethanamine, are prepared and their DNA binding and photocleavage activity in visible light studied. Complexes 2, 4, 5 and 6a that are structurally characterized by X-ray crystallography show distorted octahedral geometry with the terpyridyl ligands binding to the metal in a meridional fashion, with Fc-dpa in 6a showing a facial binding mode. The Fc-tpy complexes display a charge transfer band in the visible region. The ferrocenyl (Fc) complexes show a quasi-reversible Fc+-Fc redox couple within 0.48 to 0.66 V vs. SCE in DMF-0.1 M TBAP. The DNA binding constants of the complexes are 104 M-1. Thermal denaturation and viscometric data suggest DNA surface binding through electrostatic interaction by the positively charged complexes. Barring the Cu(II) complex 3, the complexes do not show any chemical nuclease activity in the presence of glutathione. Complexes 1-4 exhibit significant plasmid DNA photocleavage activity in visible light via a photoredox pathway. Complex 5, without the Fc moiety, does not show any DNA photocleavage activity. The Zn(II) complex 4 shows a significant PDT effect in HeLa cancer cells giving an IC50 value of 7.5 µ M in visible light, while being less toxic in the dark (IC50 = 49 µ M)

Colocalization of intranuclear lamin foci with RNA splicing factors

The lamins form a fibrous network underlying the inner nuclear membrane termed the nuclear lamina. In order to gain insights into the role of lamins in nuclear organization, we have characterized a monoclonal antibody (LA-2H10) raised against recombinant rat lamin A that labels nuclei in a speckled pattern in all cells of unsynchronized populations of HeLa and rat F-111 fibroblast cells, unlike the typical nuclear periphery staining by another monoclonal antibody to lamin A, LA-2B3. In immunolocalization studies the lamin A speckles or foci were found to colocalize with the RNA splicing factors SC-35 and U5-116 kD, but not with p80 coilin found in coiled bodies. Lamin B1 was also associated with these foci. These foci dispersed when cells entered mitosis and reformed during anaphase. The differential reactivity of LA-2H10 and LA-2B3 was retained after nuclei were extracted with detergents, nucleases and salt to disrupt interactions of lamins with chromatin and other nuclear proteins. Using deletion fragments of recombinant lamin A, the epitope recognized by LA-2H10 was located between amino acids 171 and 246. Our findings are consistent with a structural role for lamins in supporting nuclear compartments containing proteins involved in RNA splicing

The Bivariate Rogers-Szeg\"{o} Polynomials

We present an operator approach to deriving Mehler's formula and the Rogers formula for the bivariate Rogers-Szeg\"{o} polynomials $h_n(x,y|q)$. The proof of Mehler's formula can be considered as a new approach to the nonsymmetric Poisson kernel formula for the continuous big $q$-Hermite polynomials $H_n(x;a|q)$ due to Askey, Rahman and Suslov. Mehler's formula for $h_n(x,y|q)$ involves a ${}_3\phi_2$ sum and the Rogers formula involves a ${}_2\phi_1$ sum. The proofs of these results are based on parameter augmentation with respect to the $q$-exponential operator and the homogeneous $q$-shift operator in two variables. By extending recent results on the Rogers-Szeg\"{o} polynomials $h_n(x|q)$ due to Hou, Lascoux and Mu, we obtain another Rogers-type formula for $h_n(x,y|q)$. Finally, we give a change of base formula for $H_n(x;a|q)$ which can be used to evaluate some integrals by using the Askey-Wilson integral.Comment: 16 pages, revised version, to appear in J. Phys. A: Math. Theo

Aspects of sustainability in the destination branding process: a bottom-up approach

The concept of sustainability is based on the premise that the inhabitants of a destination should be involved in the way that destination is managed and promoted. At the same time, the literature of place branding emphasizes the important role of local stakeholders in the creation of a true and reliable place brand. In fact, the process of developing a destination brand begins with the aim of shaping the identity of a destination; what the destination stands for. The sustainable dimensions of the destination branding process are explored, while focus groups and structured questionnaires are used to evaluate the usefulness of projection techniques in the process of building a brand identity. It seems that the use of the personification technique could work as an effective destination positioning exercise and as an alternative proposal to the outdated clichés used in tourism promotion

A Comparative Study of Leptospirosis and Dengue in Thai Children

Two of the most common causes of acute febrile illnesses among children in the tropics are leptospirosis and dengue. Early in illness, these two conditions are often indistinguishable and rapid laboratory confirmation of the infecting pathogen is generally not available. An enhanced ability to distinguish leptospirosis from dengue in children would guide clinicians and public health personnel in the appropriate use of limited healthcare resources

Laparoscopic anterior gastropexy for chronic recurrent gastric volvulus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Gastric volvulus is an uncommon clinical entity, first described by Berti in 1866. It is a rotation of all or part of the stomach through more than 180°. This rotation can occur on the longitudinal (organo-axial) or transverse (mesentero-axial) axis. This condition can lead to a closed-loop obstruction or strangulation. Traditional surgical therapy for gastric volvulus is based on an open approach. Here we report the case of a patient with chronic intermittent gastric volvulus who underwent a successful laparoscopic treatment.</p> <p>Case presentation</p> <p>A 34-year-old woman presented with multiple episodes of recurrent upper abdominal pain associated with retching and vomiting, treated unsuccessfully with intramuscular metoclopramide. Endoscopic examination of the upper digestive tract showed a suspected rotation of the stomach, and a chronic recurrent gastric volvulus was revealed by barium meal. The patient was operated on successfully, with an anterior laparoscopic gastropexy performed as the first surgical approach.</p> <p>Conclusion</p> <p>Experience with laparoscopic anterior gastropexy is limited only to a few described cases. Our patient was clinically and radiologically followed-up for 2 years with no evidence of recurrence, either radiological or symptomatic. Based on this result, laparoscopic gastropexy can be seen and considered as an initial 'gold standard' for the treatment of gastric volvulus.</p

Adjuvant Properties of Thermal Component of Hyperthermia Enhanced Transdermal Immunization: Effect on Dendritic Cells

Hyperthermia enhanced transdermal (HET) immunization is a novel needle free immunization strategy employing application of antigen along with mild local hyperthermia (42°C) to intact skin resulting in detectable antigen specific Ig in serum. In the present study, we investigated the adjuvant effect of thermal component of HET immunization in terms of maturation of dendritic cells and its implication on the quality of the immune outcome in terms of antibody production upon HET immunization with tetanus toxoid (TT). We have shown that in vitro hyperthermia exposure at 42°C for 30 minutes up regulates the surface expression of maturation markers on bone marrow derived DCs. This observation correlated in vivo with an increased and accelerated expression of maturation markers on DCs in the draining lymph node upon HET immunization in mice. This effect was found to be independent of the antigen delivered and depends only on the thermal component of HET immunization. In vitro hyperthermia also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell response. HET immunization also induced a systemic T cell response to TT, as suggested by proliferation of splenocytes from immunized animal upon in vitro stimulation by TT. Exposure to heat during primary immunization led to generation of mainly IgG class of antibodies upon boosting, similar to the use of conventional alum adjuvant, thus highlighting the adjuvant potential of heat during HET immunization. Lastly, we have shown that mice immunized by tetanus toxoid using HET route exhibited protection against challenge with a lethal dose of tetanus toxin. Thus, in addition to being a painless, needle free delivery system it also has an immune modulatory potential