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Biomedical subjects

N Khalil

Publications and source records attributed to N Khalil.

At least 37 records · Page 2Linked to original sources
PubMed1994

Fetal liver hemangioma and chorioangioma: two unusual cases of severe fetal anemia detected by ultrasonography and its perinatal management.

Severe anemia was diagnosed by cordocentesis in two fetuses, one with a large chorioangioma, the other with a liver hemangioma. Despite the presence of a chronic fetotumoral shunt, both cases were partly treated by a fetal intravascular transfusion, followed by an elective Cesarean section. This 'predelivery' management of anemia should improve neonatal morbidity associated with severe hematological and acid-base balance disorders.

Journal Article↗
PubMed1994

Regulation of type II alveolar epithelial cell proliferation by TGF-beta during bleomycin-induced lung injury in rats.

Three isoforms of transforming growth factor-beta (TGF-beta) are found in mammalian cells and are potent regulators of inflammation, connective tissue synthesis, cellular proliferation, and differentiation. To determine the distribution and regulation of TGF-beta isoforms during pulmonary injury, a rat model of bleomycin-induced lung inflammation and repair was used. Using immunohistochemistry, we demonstrate that TGF-beta 2 and TGF-beta 3 were localized to alveolar macrophages as well as epithelial and smooth muscle cells of both normal rat lungs and rat lungs obtained at all time intervals after bleomycin administration. Early in bleomycin-induced lung injury, when there is active proliferation of type II alveolar epithelial cells, there was an increase in the number of type II alveolar epithelial cells isolated per lung and an increase in DNA synthesis by explanted type II alveolar epithelial cells. At this time, the secretion of biologically active TGF-beta 1-3, which are potent inhibitors of epithelial cell proliferation, was decreased. However, the secretion of TGF-beta 1-3 activity was markedly increased later in the injury response and coincided with a reduction in the number of type II alveolar epithelial cells isolated per lung and DNA synthesis in vitro. Furthermore, the addition of TGF-beta 1, 2, and 3 to cultures of actively proliferating type II alveolar epithelial cells resulted in inhibition of [3H]thymidine incorporation, whereas, in the presence of anti-TGF-beta 1-3 antibody, there was an increase in [3H]thymidine incorporation. Our findings suggest that altered secretion of TGF-beta 1-3 activity by type II alveolar epithelial cells during bleomycin-induced lung injury may regulate pulmonary alveolar epithelial cell proliferation during injury and repair phases.

Animals↗
PubMed1993

Regulation of alveolar macrophage transforming growth factor-beta secretion by corticosteroids in bleomycin-induced pulmonary inflammation in the rat.

In a model of pulmonary inflammation and fibrosis induced by the antineoplastic antibiotic, bleomycin, we previously demonstrated that TGF-beta was markedly elevated within 7 d of bleomycin administration. At the time of maximal TGF-beta production, TGF-beta 1 was localized by immunohistochemistry to be present almost exclusively in alveolar macrophages. In this study, we have demonstrated that alveolar macrophages stimulated by bleomycin-induced injury secrete large quantities of biologically active TGF-beta 1 when explanted into tissue culture. However, alveolar macrophages from normal saline-treated rats secrete small quantities of biologically inactive TGF-beta. In contrast, splenic macrophages secrete large quantities of inactive TGF-beta and are unaffected by the intratracheal bleomycin treatment. High doses of the corticosteroid methylprednisolone given intramuscularly before and concomitantly with bleomycin administration prevented the influx of alveolar macrophages into the lungs, diminishing both the number of macrophages present in the alveoli and the total lung content of TGF-beta. However, the rate of secretion of TGF-beta by alveolar macrophages recovered from the alveoli was unchanged after corticosteroid treatment. When activated alveolar macrophages were cultured in the presence of several concentrations of dexamethasone that completely suppressed IL-1 secretion, little effect on TGF-beta secretion was observed. The findings in this study demonstrate that during bleomycin-induced injury, alveolar macrophages not only secrete large quantities of active TGF-beta 1, but are a predominant source of the enhanced TGF-beta response seen in this model. Furthermore, the alveolar macrophage secretion of TGF-beta is not inhibited by the presence of high concentrations of corticosteroids.

Animals↗
PubMed1993

[Child rearing style, social behavior dimensions and severity of schizophrenic illness].

In a sample of 53 schizophrenic patients, perceived parental rearing attitudes were rated with the EMBU inventory, the quality of relationship to key relatives was measured with the AfS, and social anxiety was assessed with the U-Scale. The values obtained were intercorrelated and compared with selected parameters for disease severity: age at first hospital admission, number of treated episodes, and duration of inpatient treatment. The results show that disease parameters rather than parental rearing behaviour determine the quality of contact with key relatives. Rearing patterns more likely influence the age at first hospital admission and social anxiety. The findings further suggest that, considering the length of "face-to-face" contact, the quality of the relationships between the schizophrenic patients and their key relatives is likely to be associated with the duration of inpatient treatment. The results of the explorative study confirm the importance of family intervention programmes.

Adolescent↗
PubMed1992

Autocrine induction of tumor protease production and invasion by a metallothionein-regulated TGF-beta 1 (Ser223, 225).

An expression vector was constructed in which TGF-beta 1 was placed under the control of the metallothionein promoter. Cys223 and Cys225 in the TGF-beta 1 propeptide were converted to serines, mutations which result in dissociation of the pro-peptide and secretion of bioactive TGF-beta 1 [Brunner, A.M., Marquardt, H., Malacko, A.R., Lioubin, M.N. and Purchio, A.F. (1989) J. Biol. Chem., 264, 13660-13664]. A fibrosarcoma was transfected with this plasmid and a clone (17.18) was selected in which TGF-beta 1 mRNA was able to be induced six-fold following zinc sulphate treatment. These cells increased the secretion of bioactive TGF-beta 1 14-fold and exhibited a coincidental increase in jun-B mRNA expression, suggesting that secreted TGF-beta 1 was acting to induce this early response gene by autocrine activation. Following zinc sulphate induction, the tumor cells became progressively more motile and able to invade collagen gels. In contrast to parental tumor not bearing the TGF-beta 1 expression vector, zinc sulphate stimulation of clone 17.18 enhanced collagenase IV and procathepsin L mRNA levels and enhanced the secretion of many collagenolytic proteases into the medium. Since the action of TGF-beta generally decreases proteolysis by suppression of protease transcription, we compared the response of normal parental fibroblasts to ras-transformed fibrosarcomas and confirmed that TGF-beta could greatly enhance collagenase IV and procathepsin L mRNA levels while having little effect on non-transformed fibroblasts. These experiments indicate that induction of TGF-beta secretion can enhance motility and protease production through autocrine activation, thus increasing the invasion potential of fibrosarcomas.

Amino Acid Sequence↗
PubMed1992

Do perceived parental rearing patterns influence social behaviour dimensions and disease severity in schizophrenia?

In an explorative study, a clinical sample of 53 schizophrenic patients was examined. The EMBU inventory was used for measuring perceived parental rearing practices, the AfS for rating the quality of relationship to key relatives and the U-Scale for assessing social anxiety. The findings obtained were intercorrelated and compared with 3 selected parameters of disease severity: age at first hospitalization, number of treated episodes and length of hospital stay. The results suggest that the quality of contact with key relatives is determined to a larger extent by the schizophrenia than by parental rearing attitudes. Rearing behaviour more likely influences the age at first hospitalization and social anxiety, whereas considering the length of face-to-face contact, the quality of the relationships between patients and their key relatives can be assumed to be associated with the duration of hospital stays.

Adolescent↗
PubMed1991

The role of TGF-beta in pulmonary fibrosis.

Pulmonary fibrosis is an irreversible accumulation of connective tissue in the interstitium of the lung. The pathogenesis of pulmonary fibrosis is not well understood. Research on animal models and studies of human lung disease suggest the initiating events may be a combination of pulmonary injury and the recruitment of inflammatory cells, mainly macrophages. A number of well characterized cytokines, including TGF-beta, have been either found in the injured lung or produced by inflammatory cells removed from the lung. In an animal model of pulmonary fibrosis, TGF-beta production is increased prior to collagen synthesis and is mainly produced by alveolar macrophages. In advanced idiopathic pulmonary fibrosis, a human fibrotic lung disease, extensive TGF-beta deposition can be detected by immunohistochemical staining, primarily in epithelial cells in areas of lung regeneration and remodelling. This suggests that the pathogenesis of the progressive fibrosis characteristic of this lung disease may be an aberrant repair process.

Bleomycin↗
PubMed1991

Transcranial stab wounds: morbidity and medicolegal awareness.

In this series of eight patients with transcranial stab wounds, the importance of classifications of such wounds as a separate traumatic entity is stressed. The mechanisms of neuronal and vascular damage in these wounds are discussed and are found to be specific from other head injuries. Cerebral injury by stabbing is largely restricted to the wound tract. Frontal stabs (two cases) are accompanied by the least morbidity and mortality, while temporal stabs (four cases) are more commonly fatal. In transorbital stabs (two cases) carotid-cavernous fistulae resulted. Early recognition, administration of antitetanus serum and antibiotics, and debridement may minimize complications.

Adult↗
PubMed1991

Increased production and immunohistochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis.

Transforming growth factor-beta (TGF-beta) can regulate cell growth and differentiation as well as production of extracellular matrix proteins. Elevated production of TGF-beta has been associated with human and rodent chronic inflammatory and fibrotic diseases. Using immunohistochemical staining, we have examined lung sections of patients with advanced idiopathic pulmonary fibrosis (IPF), a disease characterized by chronic inflammation and fibrosis and demonstrated a marked and consistent increase in TGF-beta production in epithelial cells and macrophages when compared to patients with nonspecific inflammation and those with no inflammation or fibrosis. In patients with advanced IPF, intracellular staining with anti-LC (1-30) TGF-beta antibody was seen prominently in bronchiolar epithelial cells. In addition, epithelial cells of honeycomb cysts and hyperplastic type II pneumocytes stained intensely. Anti-CC (1-30) TGF-beta antibody, which reacts with extracellular TGF-beta, was localized in the lamina propria of bronchioles and in subepithelial regions of honeycomb cysts in areas of dense fibroconnective tissue deposition. The close association of subepithelial TGF-beta to the intracellular form in advanced IPF suggests that TGF-beta was produced and secreted primarily by epithelial cells. Because of the well-known effects of TGF-beta on extracellular matrix formation and on epithelial cell differentiation, the increased production of TGF-beta in advanced IPF may be pathogenic to the pulmonary fibrotic and regenerative responses seen in this disease.

Biopsy↗
PubMed1990

Growth factor-initiated proliferation of mouse embryonic fibroblasts induces cytotoxicity by natural killer cells and by a non-cytolysin cytotoxin in natural killer granules.

NK cells preferentially kill normal embryonic fibroblasts. Because embryonic cells are growth factor responsive and maintain high proliferative rates, we examined the requirement for growth factor-initiated proliferation for NK susceptibility. Murine embryonic fibroblasts made quiescent in defined medium lacking growth factors were relatively resistant to NK cytolysis. However, reinitiation of proliferation with basic fibroblast growth factor (bFGF) or epidermal growth factor enhanced lysis in a dose-dependent fashion. TGF-beta, which blocked cell division, did not enhance cytotoxicity. Additionally, growth inhibition by prolonged incubation at confluence suppressed lysis. The enhanced NK cytotoxicity of bFGF-stimulated fibroblasts was caused by a post-binding event because no difference in cold target inhibition could be demonstrated with bFGF-treated cells. NK cytotoxicity has largely been attributed to the action of cytotoxins released from cytoplasmic granules. In a 51Cr release assay, bFGF-treated fibroblasts were insensitive to NK granules isolated from the RNK large granular lymphocyte leukemia. However, these same cells exhibited marked sensitivity to lysis in an 18-h adhesion assay normally utilized to detect TNF-alpha. With the use of this assay, a dose-dependent increase in sensitivity of bFGF-treated fibroblasts was observed, whereas quiescent fibroblasts were resistant to the action of isolated NK granules. Granule cytotoxicity was not caused by cytolysin/perforin because inactivation of granule hemolytic activity with CaCl2 did not affect fibroblast killing, and bFGF-treated cells were insensitive to purified cytolysin/perforin. This suggested that another granule associated cytotoxin was responsible for enhanced NK sensitivity of actively proliferating fibroblasts.

Animals↗
PubMed1990

RR interval variation and the sympathetic skin response in the assessment of autonomic function in peripheral neuropathy.

The diagnostic value of two simple tests of autonomic function, the RR interval variation and the sympathetic skin response, was evaluated relative to symptoms of dysautonomia in 53 patients with peripheral neuropathy. Of 22 patients with peripheral neuropathy and clinical dysautonomia, 15 showed abnormal results on both tests, and 7 had abnormal results on one test only. In none of the patients with dysautonomia were both tests' results normal. Conversely, all 15 patients with abnormal results of both sympathetic skin response and RR interval variation had symptoms of dysautonomia, while 7 of 15 patients with abnormalities limited to one test had such symptoms. No patient with normal results on both tests had clinical dysautonomia. These data indicate that RR interval variation and sympathetic skin response, both of which can easily be performed in the electromyography laboratory, are helpful in combination in the assessment of autonomic function in peripheral neuropathies.

Adolescent↗
PubMed1990

Shunt for bypass graft of the cavernous carotid artery: an anatomical and technical study.

During direct surgery of neoplastic and vascular lesions of the cavernous sinus, the intracavernous carotid artery may be injured beyond repair, or its total isolation may be necessary for surgical management of these lesions. The newly developed procedure of a saphenous vein graft bypass of the cavernous carotid artery allows re-establishment of carotid circulation. Patients with poor collateral circulation are at high risk for ischemic complications induced by the prolonged temporary occlusion required to perform the bypass graft. Optimal management of these patients is to perform the venous bypass graft for permanent vascularization while maintaining carotid cerebral circulation through an intraoperative shunt. We studied this procedure in cadavers, and three shunt types were evaluated: the external intrapetrous-supraclinoid shunt (Type A), the internal intrapetrous-supraclinoid shunt (Type B), and the neck internal carotid-supraclinoid shunt (Type C). Anatomical landmarks, techniques, distances, caliber, and materials used are presented. The rationale and candidates for such a procedure are discussed. The specifications of an optimal balloon shunt are presented, and the three procedures are compared.

Anastomosis, Surgical↗
PubMed1989

Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation.

A rat model of bleomycin-induced pulmonary inflammation and fibrosis was used to examine the relationship between collagen synthesis and transforming growth factor beta (TGF-beta) production, and cellular distribution. Total lung TGF-beta was elevated within 2 h of intratracheal bleomycin administration and peaked 7 d later at levels 30-fold higher than controls. This was followed by a gradual decline with lower but persistent levels of production in the late phase of the response between 21 and 28 d later. The peak TGF-beta levels preceded the maximum collagen and noncollagen protein synthesis measured by [3H]proline incorporation into lung fibroblast explants of bleomycin-treated rats. The pattern of immunohistochemical staining localized TGF-beta initially in the cytoplasm of bronchiolar epithelium cells and subepithelial extracellular matrix. The peak of lung TGF-beta levels at 7 d coincided with intense TGF-beta staining of macrophages dispersed in the alveolar interstitium and in organized clusters. Later in the course of the response. TGF-beta was primarily associated with extracellular matrix in regions of increased cellularity and tissue repair, and coincided with the maximum fibroblast collagen synthesis. This temporal and spatial relationship between collagen production and TGF-beta production by macrophages suggests an important if not primary role for TGF-beta in the pathogenesis of the pulmonary fibrosis.

Animals↗
PubMed1989

Natural killer cell regulation of murine embryonic pulmonary fibroblast survival in vivo.

We examined the role of the natural killer (NK) cell in controlling the survival of embryonic pulmonary fibroblasts in vivo. In vitro, both primary embryonic fibroblasts and an embryonic fibroblast line (10T1/2) were lysed by syngeneic C3H/HeN splenocytes threefold more efficiently than primary adult fibroblasts. The membrane phenotype of the effector cells was typical of NK cells. It was asialo GM1+, Lyt2.1-, Lyt 1.1-, Thy 1.2-. The cytotoxicity of the effector cell could be enhanced by IFN-alpha/beta but was deficient in the C3H/HeJ bg/bg mutant. Iododeoxyuridine (131I-dUrd)-labeled embryonic fibroblasts were injected intravenously into syngeneic mice with either enhanced or deficient NK function and their survival in the lung was quantitated. Enhanced fibroblast survival was detected in the NK deficient C3H/HeJ beige (bg/bg) mutant strain compared to its normal littermate C3H/HeJ (bg/+). A second method of NK depletion by pretreatment with rabbit anti-asialo GM1 antiserum also produced a striking increase in fibroblast survival. Poly(I:C) significantly enhanced the elimination of pulmonary fibroblasts from the lung between 4 and 24 hr after injection. Poly(I:C) did not enhance clearance of pulmonary fibroblasts in the C3H/HeJ (bg/bg) mutant, but did so in the normal littermate C3H/HeJ (bg/+). In conclusion, we have shown that the survival of embryonic pulmonary fibroblasts was inversely correlated with in vivo NK activity suggesting a possible role for this cytotoxic cell in the control of fibroblast growth in vivo.

Animals↗
PubMed1987

Teacher awareness program on child abuse: a randomized controlled trial.

Teachers have a significant role in preventing, detecting and reporting child abuse and neglect. They are hindered in fulfilling this role by a serious lack of knowledge of the law, of school board policies, and of maltreatment. A comprehensive professional development workshop was developed and presented to elementary school teachers. The package was evaluated by means of a randomized controlled trial. The workshop proved to be effective in increasing and maintaining knowledge.

Awareness↗
PubMed1987

Lumbrical sparing in carpal tunnel syndrome: anatomic, physiologic, and diagnostic implications.

Motor axons supplying lumbrical muscles are less severely affected than axons supplying thenar muscles in the carpal tunnel syndrome; sometimes lumbrical motor fibers are less affected than digit 2 sensory fibers. This pattern is consistent with compression of both the anterior and posterior aspects of the median nerve in the carpal tunnel because nerve fibers responsible for thenar, lumbrical, and digit 2 functions lie in an anterior-posterior gradient within the distal median nerve. Recognition of lumbrical sparing supports the electrodiagnosis of carpal tunnel syndrome when the distal latency to thenar muscles or the palm-to-wrist mixed median nerve conduction velocity is normal.

Action Potentials↗