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Biomedical subjects

N I Khan

Publications and source records attributed to N I Khan.

14 recordsLinked to original sources

Cripto-1 enhances migration and branching morphogenesis of mouse mammary epithelial cells.

Cripto-1 is an EGF-CFC protein that performs an important role during early vertebrate development and is overexpressed in several types of human cancer. In the present study mouse EpH4, NMuMG, and TAC-2 mammary epithelial cells that are negative for endogenous cripto-1 expression were transfected with the murine cripto-1 cDNA. Cripto-1-transfected cell lines exhibited functional and physiological differences from the original cell lines including enhanced anchorage-independent growth in soft agar (EpH4 cells), growth in serum-free medium, increased proliferation, and formation of branching, duct-like structures when grown in a three-dimensional collagen type I matrix. Furthermore, cripto-1-expressing cell lines showed elevated migration in vitro in Boyden chamber and wound-healing assays. These results indicate that cripto-1 can function through an autocrine pathway that enables mammary epithelial cells to undergo an epithelial to mesenchymal transition.

Animals↗

Identification of Cripto-1 in human milk.

Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related peptide that plays an important role in normal mammary gland development. CR-1 is expressed in the growing terminal end buds in the virgin mouse mammary gland and its expression increases during pregnancy and lactation. Furthermore, CR-I is involved in the early stages of mouse mammary tumorigenesis and in the pathogenesis of human breast cancer. Since CR-1 is expressed in the mouse mammary gland at high levels during pregnancy and lactation, we have evaluated whether this protein is present in human milk. In the present study we demonstrate that a 28 kDa immunoreactive CR-1 protein is present in 24 human milk samples as assessed by western blot analysis and that by enzyme-linked immunosorbent assay the concentration of CR-1 ranges between 62 and 118 ng/ml. In addition, CR-1 that had been purified from human milk is able to stimulate the phosphorylation of mitogen activated protein kinase in nontransformed NMuMG mouse mammary epithelial cells. These results suggest that CR-1 in human milk may be important in regulating mammary gland development during pregnancy and lactation.

Animals↗

The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer.

The EGF-CFC gene family encodes a group of structurally related proteins that serve as important competence factors during early embryogenesis in Xenopus, zebrafish, mice and humans. This multigene family consists of Xenopus FRL-1, zebrafish one-eyed-pinhead (oep), mouse cripto (Cr-1) and cryptic, and human cripto (CR-1) and criptin. FRL-1, oep and mouse cripto are essential for the formation of mesoderm and endoderm and for correct establishment of the anterior/posterior axis. In addition, oep and cryptic are important for the establishment of left-right (L/R) asymmetry. In zebrafish, there is strong genetic evidence that oep functions as an obligatory co-factor for the correct signaling of a transforming growth factor-beta (TGFbeta)-related gene, nodal, during gastrulation and during L/R asymmetry development. Expression of Cr-1 and cryptic is extinguished in the embryo after day 8 of gestation except for the developing heart where Cr-1 expression is necessary for myocardial development. In the mouse, cryptic is not expressed in adult tissues whereas Cr-1 is expressed at a low level in several different tissues including the mammary gland. In the mammary gland, expression of Cr-1 in the ductal epithelial cells increases during pregnancy and lactation and immunoreactive and biologically active Cr-1 protein can be detected in human milk. Overexpression of Cr-1 in mouse mammary epithelial cells can facilitate their in vitro transformation and in vivo these Cr-1-transduced cells produce ductal hyperplasias in the mammary gland. Recombinant mouse or human cripto can enhance cell motility and branching morphogenesis in mammary epithelial cells and in some human tumor cells. These effects are accompanied by an epithelial-mesenchymal transition which is associated with a decrease in beta-catenin function and an increase in vimentin expression. Expression of cripto is increased several-fold in human colon, gastric, pancreatic and lung carcinomas and in a variety of different types of mouse and human breast carcinomas. More importantly, this increase can first be detected in premalignant lesions in some of these tissues. Although a specific receptor for the EGF-CFC proteins has not yet been identified, oep depends upon an activin-type RIIB and RIB receptor system that functions through Smad-2. Mouse and human cripto have been shown to activate a ras/raf/MAP kinase signaling pathway in mammary epithelial cells. Activation of phosphatidylinositol 3-kinase and Akt are also important for the ability of CR-1 to stimulate cell migration and to block lactogenic hormone-induced expression of beta-casein and whey acidic protein. In mammary epithelial cells, part of these responses may depend on the ability of CR-1 to transactivate erb B-4 and/or fibroblast growth factor receptor 1 through an src-like tyrosine kinase.

Amino Acid Sequence↗

[Reoperations in bradyarrhythmic forms of disorders of heart conductivity].

Under analysis were causes of reoperations in bradyarrhythmic forms of disturbances of conductivity of the heart. 565 operations connected with electrocardiostimulation were performed on 276 patients. Reoperations in patients with the myocardial stimulation were made on 63 patients, with the endocardial stimulation--in 226 patients. Causes of reoperations were as follows: depletion of the source of ECS--31.5%; dislocation of the electrode--8.2%; damage of the electrode--15%, suppuration of the bed, decubitus of the stimulator--28.8%; competing rate--7.4%; break of the contact in the connecting system of the electrode and cardiostimulator--9.4%.

Bradycardia↗

Visceral leishmaniasis and its control in Bangladesh.

Visceral leishmaniasis, which is also known as kala-azar, reappeared in Bangladesh during the 1980s, approximately 7-8 years after large-scale use of DDT had been abandoned by the malaria eradication programme in the country. Pabna, Mymensingh and Rajshahi were the regions most affected with kala-azar. The article presents a historical review and information about the present status of leishmaniasis in Bangladesh together with control strategies and a proposed plan of operation.

Adolescent↗

A comparison of counterimmunoelectrophoresis and indirect haemagglutination tests for the immunoepidemiological investigation of kala-azar.

Counterimmunoelectrophoresis (CIE) using cell-free extracts of Leishmania donovani promastigotes and Trypanosoma brucei as antigens and indirect haemagglutination (IHA) using commercially prepared reagents were compared for their diagnostic efficacy and applicability to immunoepidemiological studies in an area of Bangladesh where kala-azar is present. The CIE was positive for all parasitologically confirmed cases whereas the IHA positivity was only 60%. The T. brucei antigen was equally as good, if not better, than the L. donovani antigen for CIE. The CIE test was negative for all of 34 apparently healthy villagers. For this same group of individuals, 10 (29%) were low titre-IHA positive. The findings suggest that CIE is the more reliable diagnostic test but both methods should be employed for immunoepidemiological investigations.

Counterimmunoelectrophoresis↗

[Regional pulmonary ventilation and blood flow in patients with mitral valve stenosis according to radionuclide study].

It is shown, on the basis of ventilation and perfusion scintigraphy, that marked pulmonary flow redistribution from basal to apical departments, combined with relatively normal distribution of ventilation volumes, is a regular feature of mitral stenosis combined with pulmonary hypertension. The quantitative assessment of the intensity of pulmonary perfusion redistribution can be used as a measure of pulmonary hypertension. Also, a right-to-left unbalance was established in the pulmonary flow distribution, manifested as hyperperfusion of the left lung.

Adolescent↗

[Effect of balanced anesthesia on lung histamine release in patients operated on for mitral heart defects with varying degrees of pulmonary hypertension].

The histamine concentration was estimated in the mixed venous and arterial blood in 28 patients with mitral defects subjected to closed mitral commissurotomy under balanced anesthesia. The oxygen content was determined simultaneously and the amount of blood shunting in the lungs was calculated by the oxygen method. It was established that the amount of histamine in the mixed venous blood coming to lungs was increased in patients with high degree lung hypertension. The balanced anesthesia itself did not influence the histamine concentration in the blood. The cessation of anesthesia, however, is followed by increased histamine concentration in the blood of patients with high lung hypertension. The process of blood shunting in the lungs is not controlled by histamine.

Anesthesia, Intravenous↗

[Radiocardiographic evaluation of the hemodynamic effect of mitral commissurotomy at different stages of the postoperative period].

The analysis of hemodynamic effect of closed mitral commissurotomy in 73 patients it different postoperative terms is presented. Within the first day after operation a dramatic hyperfunction of the myocardium was observed in patients with the 3d stage of blood circulation disorders. In patients with the 4th stage of the disease mitral commissurotomy failed to give a positive hemodynamic effect both within the first day and at later terms. In the late postoperative period there were no substantial differences between the data of central hemodynamics and postoperative data independent of the stage of the blood circulation disturbance.

Aortic Valve Stenosis↗