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Biomedical subjects

A Mikhail

Publications and source records attributed to A Mikhail.

At least 19 recordsLinked to original sources

Prospective randomized study of various techniques of percutaneous nephrolithotomy.

OBJECTIVES: To compare the modifications of the technique of percutaneous nephrolithotomy (PCN), including "mini-PCN" and tubeless PCN, to establish which technique is associated with the least morbidity and complications. METHODS: We performed a prospective randomized trial to assess the efficacy and morbidity of each method of percutaneous renal access. Standard PCN involved tract dilation to 30F for passage of a 34F working sheath, and our "mini-PCN" involved tract dilation to 22F for passage of a 26F sheath. Tubeless PCN involved the use of a double-J stent for internal drainage without the use of a nephrostomy tube for external drainage at termination of the procedure. Thirty patients (10 patients in each group) were enrolled, and 27 patients completed the study. All three groups were compared with regard to postoperative pain using a validated pain questionnaire comprised of a visual analogue scale and a verbal rating scale. The operative time, estimated blood loss, stone burden, procedure success rate, stone-free rate, length of hospitalization, total procedural cost, and complications were also compared for each technique. RESULTS: The tubeless PCN population required less morphine use, had a decreased length of hospitalization, and had a smaller total procedural cost compared with the other two groups. One complication was noted in both the standard and mini-PCN groups, consisting of renal bleeding requiring a 2 and 3-U blood transfusion in the standard and mini-PCN groups, respectively. CONCLUSIONS: The tubeless technique is associated with the least amount of morbidity and the greatest cost efficiency compared with the other techniques. No overall advantage was found for the mini-PCN versus the standard technique, but the mini-PCN is at a slight disadvantage because of poorer visualization and optics and difficulty with use of the nephroscopic graspers.

Cost-Benefit Analysis↗

Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway activates IkappaB kinases (IKK-alpha/beta) and IKK-beta is a developmentally regulated protein kinase.

Nuclear factor kappa-B (NF-kappaB) is a pleiotropic transcription factor that plays a central role in the immune and inflammatory responses, and is also involved in controlling viral transcription and apoptosis. A critical control in the activation of NF-kappaB is the phosphorylation of its inhibitory factor IkappaBs by IkappaB kinases (IKK-alpha and -beta). Here, we present experiments addressing the regulation and global expression of murine IKK-beta, and localize the IKK-beta gene to mouse chromosome 8A3-A4. IKK-beta was expressed primarily in the liver, kidney and spleen, and at lower levels in the other adult tissues. While IKK-beta was expressed ubiquitously throughout the mouse embryo at 9.5 days, its expression began to be localized to the brain, neural ganglia, neural tube, and liver in the 12.5-day's embryo. At 15.5 days, the expression of IKK-beta was further restricted to specific tissues of the embryo, suggesting that IKK-beta is a developmentally regulated protein kinase. Interestingly, IKK-beta phosphorylated IkappaB constitutively, whereas IKK-alpha was not active in the absence of cell stimulation. Moreover, both IKK-alpha and -beta were activated by hematopoietic progenitor kinase-1 (HPK1) and MAPK/ERK kinase kinase-1 (MEKK1) specifically, suggesting that IkappaB/NF-kappaB is regulated through the HPK1-MEKK1 stress response signaling pathway.

Amino Acid Sequence↗

Murine p38-delta mitogen-activated protein kinase, a developmentally regulated protein kinase that is activated by stress and proinflammatory cytokines.

The p38 mitogen-activated protein kinases (MAPK) play a crucial role in stress and inflammatory responses and are also involved in activation of the human immunodeficiency virus gene expression. We have isolated the murine cDNA clones encoding p38-delta MAPK, and we have localized the p38-delta gene to mouse chromosome 17A3-B and human chromosome 6p21.3. By using Northern and in situ hybridization, we have examined the expression of p38-delta in the mouse adult tissues and embryos. p38-delta was expressed primarily in the lung, testis, kidney, and gut epithelium in the adult tissues. Although p38-delta was expressed predominantly in the developing gut and the septum transversum in the mouse embryo at 9.5 days, its expression began to be expanded to many specific tissues in the 12.5-day embryo. At 15.5 days, p38-delta was expressed virtually in most developing epithelia in embryos, suggesting that p38-delta is a developmentally regulated MAPK. Interestingly, p38-delta and p38-alpha were similar serine/threonine kinases but differed in substrate specificity. Overall, p38-delta resembles p38-gamma, whereas p38-beta resembles p38-alpha. Moreover, p38-delta is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7, suggesting that p38-delta is a unique stress-responsive protein kinase.

Amino Acid Sequence↗

Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities.

The receptor for the gene product of the obesity gene, leptin, was recently reported to be expressed on murine and human hematopoietic progenitor cells. Therefore, we studied the expression of the leptin receptor, OB-R, in normal myeloid precursors, human leukemia cell lines, and primary leukemic cells using reverse-transcriptase polymerase chain reaction. In normal hematopoiesis, OB-R was expressed in CD34(+) cells. Normal promyelocytes (CD34(-)33(+) and CD34(-)13(+)) expressed only very low levels of the short, presumably nonsignaling isoform. Both the long and short isoforms of OB-R were expressed in 10 of 22 samples from patients with newly diagnosed primary or secondary acute myeloid leukemia (AML), with a higher incidence of the long isoform in primary AML (87.6% v 28.6%; P =.01). The incidence of OB-R expression was higher in recurrent than in newly diagnosed AML (P <.001), and samples from four patients with refractory AML showed strong expression of both isoforms. Both OB-R isoforms were also expressed in newly diagnosed and recurrent acute promyelocytic leukemia cells but were essentially absent in samples of chronic or acute lymphocytic leukemia. In vitro growth of myeloid leukemic cell lines and of blasts from 14 primary AMLs demonstrated that recombinant human leptin alone induced low level proliferation, significantly (P <.05) increased proliferation induced by recombinant human granulocyte colony-stimulating factor, interleukin 3, and stem cell factor in a subset of AML and increased colony formation (P <.005). Also, leptin reduced apoptosis induced by cytokine withdrawal in MO7E and TF-1 cells. Serum leptin levels correlated only with body mass index (P <. 001) and gender (P =.03). Results confirm the reported expression of leptin receptor in normal CD34(+) cells and demonstrate the frequent expression of leptin receptors in AML blasts. While normal promyelocytes lack receptor expression, leukemic promyelocytes express both isoforms. We also demonstrate proliferative effects of leptin alone and in combination with other physiologic cytokines, and anti-apoptotic properties of leptin. These findings could have implications for the pathophysiology of AML.

Apoptosis↗

Cloning and characterization of developmental endothelial locus-1: an embryonic endothelial cell protein that binds the alphavbeta3 integrin receptor.

We have taken advantage of an enhancer trap event in a line of transgenic mice to identify a unique developmentally regulated endothelial cell locus (Del1). The protein encoded in this locus contains three EGF-like repeats homologous to those in Notch and related proteins, including an EGF-like repeat that contains an RGD motif, and two discoidin I-like domains. Del1 is shown to be a matrix protein and to promote adhesion of endothelial cells through interaction with the alphavbeta3 integrin receptor. Embryonic endothelial-like yolk sac cells expressing recombinant Del1 protein, or grown on an extracellular matrix containing Del1 protein, are inhibited from forming vascular-like structures. Expression of Del1 protein in the chick chorioallantoic membrane leads to loss of vascular integrity and promotes vessel remodeling. Del1 is thus a new ligand for the alphavbeta3 integrin receptor and may function to regulate vascular morphogenesis or remodeling in embryonic development.

Amino Acid Sequence↗

Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction.

Hematopoietic development is a complex process that involves a large number of growth factors and cytokines. Many cytokines are known to act on more mature, lineage-restricted cells of the hematopoietic system. However, no specific factors have yet been identified that induce the expansion of the most primitive hematopoietic cells without also inducing differentiation. To search for such factors, we isolated novel cell lines from the yolk sac in order to identify genes important in early hematopoietic and endothelial development. This approach led to the discovery of B219, a sequence that is expressed in at least four isoforms in very primitive hematopoietic cell populations and which may represent a novel hemopoietin receptor. The recently published receptor for the obesity (ob) gene product (leptin) is an isoform of B219 with a nearly identical ligand binding domain. B219/obr is expressed in the yolk sac, early fetal liver, enriched hematopoietic stem cells and in a variety of lymphohematopoietic cell lines. B219/obr is also expressed at high levels in adult reproductive organs. B219/obr maps to human chromosome 1p32, a region syntenic with the recently reported location of obr on murine chromosome 4 (ref. 5).

Alternative Splicing↗

Risk of pneumothorax in CT-guided transthoracic needle aspiration biopsy of the lung.

PURPOSE: To determine risk factors for pneumothorax and chest tube placement associated with computed tomography (CT)-guided transthoracic needle aspiration biopsy (TNAB) of the lung. METHODS: One hundred twenty-one consecutive CT-guided TNAB procedures were performed in 117 patients. Patient age, sex, number of needle passes and pleural planes traversed, lesion size, distance of lesion from the pleura, and results of pulmonary function tests were analyzed as single and multiple dependent variables for pneumothorax and chest tube placement. RESULTS: Pneumothorax occurred in 54 of 121 procedures (44.6%); a chest tube was required in 18 cases (14.9%). Increased lesion depth was the most significant predictor of pneumothorax (P = .002). Smaller lesion size also correlated with increased risk of pneumothorax (P = .04). Among patients with pneumothorax, a significantly higher frequency of chest tube placement was seen in those with severe obstructive lung disease, as measured by percentage of predicted FEV1 (forced expiratory volume in 1 second) (51% in patients requiring a chest tube vs 81% in those not requiring a chest tube, P = .006) and FEV1/FVC (forced vital capacity) (x100) (45% vs 66%, P = .001). CONCLUSION: Increased lesion depth and smaller lesion size correlated strongly with the development of pneumothorax. Once pneumothorax occurred, chest tube placement related to the severity of the patient's obstructive lung disease.

Biopsy, Needle↗

Neurotropic desmoplastic melanoma: a rare vulvar malignancy.

Melanoma represents the second most frequent vulvar malignancy, and yet is still considered to be an uncommon neoplasm. Several varieties of melanoma exist. A patient who was diagnosed with a rare subtype of melanoma as a primary vulvar process is presented here. To date, there is only one other reported case of neurotropic desmoplastic melanoma as a primary vulvar lesion. Our management included wide local excision of the primary lesion with clinical follow-up. Microstaging of this lesion showed it to fall into the poor prognosis category as per Breslow's technique, with a thickness of 6.5 mm. Clinical follow-up has been greater than 30 months without evidence of recurrence.

Aged↗

Crystalloids in metastatic prostatic adenocarcinoma.

The authors report a case of metastatic prostate cancer masquerading as a primary lung tumor. Histologically, the lung tumor displayed eosinophilic crystalloids in the malignant glands typical of those previously described in prostatic adenocarcinoma. Review of histologic material from 30 additional patients with metastatic prostate cancer failed to reveal crystalloids in the metastases. Seven patients with histologic material from locally advanced prostatic adenocarcinoma, defined as spread to the rectum, bladder, or nonnodal pelvic soft tissue, were also reviewed. One of these patients demonstrated crystalloids in the bladder extension of locally advanced prostatic adenocarcinoma. Although rare, the presence of crystalloids may be used as strong evidence for the prostatic origin of an adenocarcinoma of uncertain origin.

Adenocarcinoma↗

Case report 808: Avulsion fracture of the greater trochanter.

The differential diagnosis of unexplained hip pain after trauma in patients with normal radiographs includes both soft tissue and bony abnormalities. We have presented a case of an isolated fracture of the greater trochanter in an adult with normal radiographs where the diagnosis was made by MRI.

Adult↗

Rapid detection of type A influenza viruses with monoclonal antibodies to the M protein (M1) by enzyme-linked immunosorbent assay and time-resolved fluoroimmunoassay.

Monoclonal antibodies (MAbs) to the M protein (M1) were used in the development of direct detection systems for type A influenza viruses in clinical specimens. Optimal detection by an enzyme-linked immunosorbent assay was achieved when MAbs were used as capture antibodies and rabbit polyclonal antibodies were used as sandwich antibodies. Detection by the enzyme-linked immunosorbent assay required amplification of the virus. direct detection in clinical specimens (nasopharyngeal aspirates) was accomplished when MAbs recognizing two distinct antigenic sites of M1 were used in a time-resolved fluoroimmunoassay. Type A influenza viruses could be detected equally well in specimens obtained during epidemics of both H3N2 and H1N1 influenza viruses.

Antibodies, Monoclonal↗

Identification of PR8 M1 protein in influenza virus high-yield reassortants by M1-specific monoclonal antibodies.

A panel of monoclonal antibodies to the M1 protein of A/PR8/34 (H1N1) (PR8) influenza A virus was found to distinguish in ELISA high-yielding reassortant viruses derived from reassortment of PR8 and X-31 (H3N2) viruses with recently prevalent field strains of H1N1 or H3N2 subtype. These findings are concordant with results of genotyping that demonstrated the presence of PR8 RNA 7 or M1 protein in high-yield reassortants by RNA or protein PAGE. All high-yield vaccine candidate reassortants Application of the M1 monoclonal antibody panel facilitates the isolation of high-yield vaccine candidate reassortants bearing the PR8 M1 gene, and should aid in epidemiologic strain tracking as well.

Antibodies, Monoclonal↗

M protein (M1) of influenza virus: antigenic analysis and intracellular localization with monoclonal antibodies.

A panel of 16 monoclonal antibodies recognizing M protein (M1) of influenza virus was generated. Competition analyses resulted in localization of 14 monoclonal antibodies to three antigenic sites. Three monoclonal antibodies localized to site 1B recognized a peptide synthesized to M1 (residues 220 to 236) with enzyme-linked immunosorbent assay titers equivalent to or greater than that seen with purified M1; therefore, site 1B is located near the C terminus of M1. Sites 2 and 3 localize to the N-terminal half of M1. Antigenic variation of M proteins was seen when the monoclonal antibodies were tested against 14 strains of type A influenza viruses. Several monoclonal antibodies showed specific recognition of A/PR/8/34 and A/USSR/90/77 M proteins and little or no reactivity for all other strains tested. Immunofluorescence analysis with the monoclonal antibodies showed migration of M protein to the nucleus during the replicative cycle and demonstrated association of M protein with actin filaments in the cytoplasm. Use of a vaccinia virus recombinant containing the M-protein gene demonstrated migration of M protein to the nucleus in the absence of synthesis of gene products from other influenza virus RNA segments.

Amino Acid Sequence↗

Detection of influenza viruses through selective adsorption and detection of the M-protein antigen.

A model system has been developed which permits rapid detection of influenza viruses through targeting of the M (membrane or matrix)-protein; a type-specific antigen, in an enzyme-linked immunosorbent assay system. This technique exploits the hydrophobic properties of M-protein; the M-protein is selectively and rapidly adsorbed to polystyrene surfaces even in the presence of a 5000-fold excess of bovine serum albumin. Hyperimmune antiserum prepared to purified M-protein is used as the detecting reagent. All type A influenza viruses could be detected by this technique, type B influenza viruses reacted to a slight extent and Sendai virus (parainfluenza virus, type 1) did not react. Virus could be detected to levels as low as 3 ng. Purification of M-protein and preparation of hyperimmune sera from other related virus groups, such as type B influenza viruses, paramyxoviruses and rhabdoviruses should permit detection of these agents by a similar technique.

Adsorption↗