Biomedical subjects

K A Mohammed

Publications and source records attributed to K A Mohammed.

At least 19 recordsLinked to original sources

PubMed2003

Mycobacteria induces pleural mesothelial permeability by down-regulating beta-catenin expression.

Patients with pulmonary tuberculosis develop pleural effusions with a high protein content. Pleural mesothelial adherens junctions promote mesothelial cell-cell adhesion and contribute to pleural integrity. In the present study we have investigated the effect of mycobacterium (BCG) on mesothelial cell adherens junction proteins and pleural permeability. BCG enhanced pleural mesothelial cell (PMC) release of vascular endothelial growth factor (VEGF), and decreased electrical resistance across the PMC monolayer. Neutralizing antibodies to VEGF significantly restored the drop in PMC electrical resistance caused by BCG. BCG infection down regulated beta-catenin (adherens junction protein) expression and caused increased permeability across confluent mesothelial monolayer. Our results suggest that in TB pleurisy, mycobacteria cause VEGF release from mesothelial cells and leads to protein exudation by altering mesothelial adherens junction proteins.

Blotting, Western↗

PubMed2001

Polar production of interleukin-8 by mesothelial cells promotes the transmesothelial migration of neutrophils: role of intercellular adhesion molecule-1.

Migration of polymorphonuclear neutrophils (PMNL) from the vascular compartment into the pleural space occurs rapidly during the development of parapneumonic effusions. This study investigated the polarized secretion of interleukin (IL)-8 in activated pleural mesothelial cells (PMC) and the migration of PMNL across resting, activated PMC monolayers. Results show that PMC produce IL-8 in a polar manner. When PMC were stimulated with Staphylococcus aureus or IL-1beta at the basal or at the apical surface, significantly (P< .05) more IL-8 was released toward the apical surface. This polarized production of IL-8 was confirmed by in situ hybridization. PMNL migration was higher from the basilar to apical than from the apical to basilar surface of PMC. Neutralizing antibodies against IL-8 and intercellular adhesion molecule (ICAM)-1 significantly (P< .001) blocked PMNL migration across activated monolayers. Thus, during pleural inflammation, PMC regulate the influx of PMNL into the pleural space by polar production of IL-8 and expression of ICAM-1.

Cell Movement↗

PubMed2001

Bacterial induction of pleural mesothelial monolayer barrier dysfunction.

Pneumonia remains one of the most common infectious causes of mortality. Patients with pneumonia develop parapneumonic effusions with a high neutrophil count as well as high protein concentrations. We hypothesized that pulmonary parenchymal bacterial infection causes a permeability change in the pleural mesothelium by inducing the production of vascular endothelial growth factor (VEGF). Complicated parapneumonic pleural effusions (empyema) have a 19-fold higher VEGF level than pleural fluids secondary to congestive heart failure and a 4-fold higher level than pleural fluids secondary to uncomplicated parapneumonic effusions. We also analyzed the influence of live Staphylococcus aureus on mesothelial barrier function using a model of confluent mesothelial monolayers. There was a significant drop in electrical resistance across S. aureus-infected pleural mesothelial cell (PMC) monolayers. Recombinant VEGF also decreases PMC electrical resistance. Neutralizing antibodies to VEGF significantly inhibited the drop in PMC electrical resistance caused by S. aureus. S. aureus infection also caused a significant increase in protein leak across confluent mesothelial monolayers. Our results suggest that bacterial pathogens induce VEGF release in mesothelial cells and alter mesothelial permeability, leading to protein exudation in empyema.

Electric Impedance↗

PubMed2001

Does long-term follow-up have a role for node negative squamous carcinoma of the vulva? The Gateshead experience.

A retrospective review was performed of 138 cases of squamous vulval cancer referred to Gateshead between 1986 and 1997, with a median follow-up of 48 months. Eighteen recurrences were detected, 11 within one year of surgery. All nine patients with groin/distant recurrence (including 4 presenting initially with local recurrence only) died of vulval cancer. Vulval pain, bleeding or other symptoms heralded all recurrences. Routine review was ineffective in detecting recurrence. Eight cases were detected by general practitioners, three by specialists, and one was self-diagnosed. Six of these had had clinical review less than two months previously. Follow-up does not appear to offer early detection or survival advantages. Patient education, with symptom-triggered rapid clinic access, may be more effective. Prospective research is indicated to assess both the effectiveness and psychological implications of routine follow-up and alternative strategies.

Adult↗

PubMed2000

Induction of acute pleural inflammation by Staphylococcus aureus. I. CD4+ T cells play a critical role in experimental empyema.

Bacterial empyema is a frequent complication of pneumonia in patients with acquired immunodeficiency syndrome (AIDS). A model of Staphylococcus aureus empyema was developed that closely resembles bacterial empyema in patients infected with human immunodeficiency virus (HIV). Results show a compartmentalized chemokine response in bacterial empyema. The chemokine levels were higher in the pleural compartment than in the peripheral circulation. Polymorphonuclear leukocyte counts, murine GRO-alpha (KC), and macrophage inflammatory protein-2 levels were significantly (P<.001) lower in CD4+ knockout (CD4 KO) mice pleural fluid than in CD4+ wild-type (CD4 WT) mice. The CD4 KO mice had poorer bacterial clearance than CD4 WT mice. During S. aureus infection, interleukin-10 levels increased in the CD4 KO mice, whereas interferon-gamma levels were increased in CD4 WT mice. CD4+ T cell depletion results in a decreased pleural chemokine response, decreased neutrophil influx into pleural space, and impaired bacterial clearance in empyema.

Animals↗

PubMed2000

MCP-1 in pleural injury: CCR2 mediates haptotaxis of pleural mesothelial cells.

Pleural injury results in the death of mesothelial cells and denudation of the mesothelial basement membrane. Repair of the mesothelium without fibrosis requires proliferation and migration of mesothelial cells into the injured area. We hypothesized that monocyte chemoattractant protein-1 (MCP-1) induces proliferative and haptotactic responses in pleural mesothelial cells (PMCs) and that the MCP-1 binding receptor CCR2 mediates the pleural repair process. We demonstrate that PMCs exhibited MCP-1-specific immunostaining on injury. MCP-1 induced proliferative and haptotactic responses in PMCs. PMCs express CCR2 in a time-dependent manner. Fluorescence-activated cell sorting analysis demonstrated that interleukin (IL)-2 upregulated CCR2 protein expression in PMCs, whereas lipopolysaccharide (LPS) downregulated the response at the initial period compared with that in resting PMCs. However, the inhibitory potential of LPS was lost after 12 h and showed a similar response at 24 and 48 h. Haptotactic migration was upregulated in PMCs that were cultured in the presence of IL-2. The increased haptotactic capacity of mesothelial cells in the presence of IL-2 correlated with increased CCR2 mRNA expression. PMCs cultured in the presence of LPS showed decreased haptotactic activity to MCP-1. Blocking the CCR2 with neutralizing antibodies decreased the haptotactic response of PMCs to MCP-1. These results suggest that the haptotactic migration of mesothelial cells in response to MCP-1 are mediated through CCR2, which may play a crucial role in reepithelialization of the denuded basement membrane at the site of pleural injury and may thus contribute to the regeneration of the mesothelium during the process of pleural repair.

Cell Division↗

PubMed2000

Talc induces apoptosis in human malignant mesothelioma cells in vitro.

Pleurodesis with talc is an accepted method for the treatment of symptomatic pleural effusions secondary to mesotheliomas. Patients with mesothelioma who have talc-induced pleurodesis have a lower morbidity than do those who do not have pleurodesis. The mechanisms whereby talc mediated these effects were considered to be secondary to a decrease or absence of a pleural effusion. The possibility that talc may directly affect malignant cells was not considered. The present study was designed to evaluate if talc directly effects cell death of malignant mesothelioma cells (MMC) or normal pleural mesothelial cells (PMC). Three confluent MMC and PMC were exposed to talc for 24, 48, and 72 h. In parallel experiments, glass beads similar in size to talc were included as control. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and DNA electrophoresis. Our results demonstrated that talc at a therapeutically achievable concentration (6 microg/cm(2)) induces significant apoptosis in MMC. Talc-induced maximum apoptosis in MMC (39.50 +/- 2.55%, 31.87 +/- 4.69%, and 15.10 +/- 3.93% in CRL-2081, CRL-5820, and CRL-5915, respectively) at 48 h, which was significantly (p < 0.05) greater than that in control cells. Electrophoresis of DNA isolated from talc-exposed MMC demonstrated the typical ladder pattern of internucleosomal DNA cleavage. Talc did not induce apoptosis in PMC, and glass beads did not cause significant apoptosis in either MMC or PMC. The present study has demonstrated that talc induces apoptosis in MMC without affecting normal mesothelial cells of the pleura.

Apoptosis↗

PubMed1999

Interleukin 8: an autocrine growth factor for malignant mesothelioma.

Interleukin 8 (IL-8) is a potent chemokine that also has a direct growth-potentiating effect on certain tumors. In the present study, we determined IL-8 levels in human malignant mesothelioma (MM) effusions and congestive heart failure pleural fluids. We also investigated antigenic IL-8 production by different MM cell lines, and we describe the role of IL-8 in the autocrine growth regulation of MMs. Mesothelial (CRL-9444 = MC) and MM (CRL-2081 = MM-1, CRL-5915 = MM-2, and CRL-5820 = MM-3) cell lines were grown using standard culture methods. The bioactive IL-8 levels were measured in supernatants of cultured cells by ELISA, and the expression of cell-associated immunoreactive IL-8 was observed by immunohistochemistry. The proliferative activity was determined by thymidine ([3H]thymidine) incorporation and also by direct cell counts after incubation with varying concentrations of IL-8 in the presence/absence of specific polyclonal IL-8 antibody. We found significantly higher levels of IL-8 in mesothelioma pleural fluids than congestive heart failure and a time-dependent increase in IL-8 levels in MM-1 and MM-2 cell supernatants during 96 h of incubation. IL-8 levels were nearly undetectable in MM-3 and MC cell line supernatants. In MM-1 and MM-2 cells, IL-8 caused a dose-dependent increase of [3H]thymidine incorporation to maximal levels of 46.3 +/- 3.6% and 12.3 +/- 1.6% (P < 0.001), respectively, when compared with serum-free medium as control. Neutralization of IL-8 significantly decreased proliferative activity of MM-1 and MM-2. IL-8 did not induce proliferative activity in MM-3 and MC cells. We conclude that IL-8 had a direct growth-potentiating activity in MMs.

Cell Division↗

PubMed1999

Mycobacterium-induced transmesothelial migration of monocytes into pleural space: role of intercellular adhesion molecule-1 in tuberculous pleurisy.

The pleural mesothelium is a dynamic cellular membrane with multiple key functions. It plays a pivotal role in pleural inflammation through its release of several cytokines and the expression of cell-surface molecules. The expression of intercellular adhesion molecule (ICAM)-1 in the pleural mesothelium of patients with active pleural tuberculosis and the role of ICAM-1 in monocyte transmigration across pleural mesothelium during tuberculous inflammation was investigated. Results indicate pleural mesothelial cells (PMCs) express ICAM-1 in tuberculous pleuritis. When PMCs were stimulated with bacille Calmette-Guérin (BCG) in vitro, they expressed ICAM-1 in a time-dependent manner. Monocyte transmigration was higher across PMC monolayers that had been stimulated with BCG. Blocking ICAM-1 on BCG-activated PMC monolayers inhibited monocyte transmigration against chemotactic gradient generated by macrophage inflammatory protein 1-alpha or monocyte chemotactic protein-1. These results indicate that ICAM-1 expression in PMCs facilitates monocyte transmigration during tuberculous pleural inflammation.

Animals↗

PubMed1999

Helper T cell type 1 and 2 cytokines regulate C-C chemokine expression in mouse pleural mesothelial cells.

The recruitment of leukocytes to an area of injury or inflammation site is one of the most fundamental host defenses. Pulmonary tuberculosis is characterized by granulomatous inflammation with an extensive infiltration of mononuclear cells. In tuberculous pleurisy pleural mesothelial cells are exposed to mycobacteria in the pleural space. In this study we demonstrate that mouse pleural mesothelial cells (PMCs), when stimulated with BCG or IFN-gamma, produced MIP-1alpha and MCP-1 in vitro. IFN-gamma enhanced the BCG-mediated MIP-1alpha and MCP-1 expression in a concentration-dependent manner. The RT-PCR studies also confirmed that both BCG and IFN-gamma induce chemokine expression. IL-4 inhibited the BCG-mediated MIP-1alpha and MCP-1 expression in a concentration-dependent manner. The lower concentrations of IL-4 were ineffective; however, at higher concentrations, the inhibitory effect of IL-4 persisted for 24 h and decreased thereafter. BCG stimulation resulted in an increase of IFN-gamma and IL-4 receptors on PMCs. Our results demonstrate that Th1 and Th2 cytokines may regulate the C-C chemokine expression in PMCs and thus play a biologically important role in mononuclear cell recruitment to the pleural space.

Animals↗

PubMed1999

Pathophysiology of pleural space infections.

The pleura responds to the presence of infecting organisms with a vigorous inflammatory response associated with an exudation of white blood cells and proteins. Changes in pleural permeability lead to formation of an exudative pleural effusion. The pleural mesothelial cell is the primary cell lining the pleural space and, when activated by the presence of organisms, initiates the inflammatory response by releasing a battery of chemokines and cytokines. Mesothelial cells are actively phagocytic and also release oxidants and proteases. The acute inflammatory process may resolve with appropriate antibiotic therapy and drainage leaving minimal fibrosis. However, under certain circumstances vigorous pleural fibrosis with scarring and loss of delineation of pleural surfaces can occur. Recognition of the stage of development of the empyema is an important clinical judgement that can affect outcome. The pathogenesis of infections of the pleural space and the role played by the various cell types is delineated in this article.

Empyema, Pleural↗

PubMed1999

Inhibition of interleukin-8 reduces human malignant pleural mesothelioma propagation in nude mouse model.

Malignant pleural mesothelioma (MPM), despite current therapeutic strategies, is still an aggressive tumor with a very poor prognosis. Interleukin-8 (IL-8), a proinflammatory and angiogenic cytokine, has an important role in tumor-related neovascularization. IL-8 has also been described to function as an autocrine growth factor. The purpose of this study was to evaluate the effect of IL-8 antibody (IL-8 Ab) on progression of MPM in vivo. Athymic nude mice (n = 65) were injected intrapleurally with human MPM cells (CRL-2081), equally divided into three groups (IL-8 Ab, control Ab, untreated), and received IP injection of IL-8 Ab, control Ab, or no treatment, respectively, every 48 h up to 15 days. Pleural fluid and serum IL-8 levels, and tumor and body weight of mice were measured following 5, 10, and 15 days of tumor injection. We found that both pleural fluid and serum IL-8 levels were significantly (P < 0.0001) lower in mice that received IL-8 Ab when compared to the other groups. In this group, lower IL-8 levels were associated with a decreased rate of tumor growth. There was a significant and direct correlation between pleural fluid IL-8 levels and tumor weight of all animals enrolled in this study (P < 0.0001, r = 0.88). We demonstrate that antibody treatment against IL-8 decreased human MPM progression. Our results suggest that treatments targeting the decrease of MPM-associated IL-8 levels or the effects of this protein may inhibit mesothelioma growth.

Animals↗

PubMed1998

Macrophage inflammatory protein-1alpha C-C chemokine in parapneumonic pleural effusions.

Parapneumonic pleural effusions are associated with the presence of a variety of inflammatory cells whose influx into the pleural space is attributed to the presence of inflammatory cytokines. Macrophage inflammatory protein-1alpha (MIP-1alpha), an important mononuclear chemokine, plays a critical role in pulmonary parenchymal inflammatory disease, but its role in the recruitment and activation of mononuclear phagocytes in the pleural space is unknown. In this study we demonstrate that complicated parapneumonic pleural effusions (empyema) and uncomplicated parapneumonic pleural effusions contain significantly (P < .001) higher levels of MIP-1alpha with higher numbers of mononuclear cells when compared with effusions resulting from malignancy and congestive heart failure. The MIP- 1alpha was biologically active and contributed 43% and 37% of the mononuclear chemotactic activity of complicated and uncomplicated parapneumonic pleural fluids, respectively. In vitro, human mesothelial cells, when stimulated with interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), or bacterial lipopolysaccharide (LPS), produced MIP-1alpha. Northern blot analysis confirmed that both endogenous (IL-1beta or TNF-alpha) and exogenous (LPS) factors induce MIP-1alpha expression in mesothelial cells. Supernatants from activated mesothelial cells demonstrated chemotactic activity for mononuclear cells. This activity was blocked by MIP-1alpha antibody, indicating that the MIP-1alpha released was biologically active. We conclude that in parapneumonic pleural effusions, MIP-1alpha plays a major but not exclusive role in the recruitment of mononuclear leukocytes from the vascular compartment to the pleural space, and pleural mesothelial cells by production of MIP-1alpha actively participate in this process.

Cell Count↗

PubMed1998

Mycobacterium-mediated chemokine expression in pleural mesothelial cells: role of C-C chemokines in tuberculous pleurisy.

Pulmonary tuberculosis is characterized by granulomatous inflammation with an extensive infiltration of mononuclear phagocytes, but the mechanisms of phagocyte recruitment to the pleural space is unknown. In this study, pleural fluid from patients with tuberculosis contained significantly (P<.001) more biologically active MIP-1alpha and MCP-1 (C-C cytokines) than did effusions from patients with congestive heart failure. Antigenic MIP-1alpha and MCP-1 was detected by immunocytochemistry in pleural biopsy sections of patients with tuberculous pleurisy. In vitro, pleural mesothelial cells stimulated with bacille Calmette-Guérin (BCG) or interferon (IFN)-gamma produced MIP-1alpha and MCP-1. Reverse transcription-polymerase chain reaction studies confirmed that both BCG and IFN-gamma induced MIP-1alpha and MCP-1 expression in mesothelial cells, demonstrating that mesothelial cell-derived C-C chemokines play a biologically important role in the recruitment of mononuclear cells to the pleural space.

Biopsy↗

PubMed1998

Talc-induced expression of C-C and C-X-C chemokines and intercellular adhesion molecule-1 in mesothelial cells.

Treatment of symptomatic carcinomatous pleural effusions is primarily directed at local palliation with a wide variety of sclerosing agents, of which talc is considered to be the most successful. The mechanism whereby talc achieves this effect is unknown. The objective of this study was to investigate whether talc stimulates pleural mesothelial cells (PMC) to release C-X-C and/or C-C chemokines and express adhesion molecules that initiate and amplify the inflammatory process in the pleural space. When PMC were challenged with talc in vitro, interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) levels were increased (p < 0.001) both at the protein and the mRNA level as compared with unstimulated cultures. Talc-stimulated PMC culture supernatant showed chemotactic activity for neutrophils and monocytes. The chemotactic activity of PMC culture supernatant was blocked by 44.2% with IL-8-specific antibody and by 55.7% with MCP-1-specific antibody, demonstrating that PMC-derived chemokines are bioactive. Talc also enhanced intercellular adhesion molecule-1 (ICAM-1) expression in PMC. The data demonstrate that talc stimulates PMC to release chemokines and express adhesion molecules that may play a critical role in pleurodesis.

Analysis of Variance↗

PubMed1998

Bacteria and viruses that cause respiratory tract infections during the pilgrimage (Haj) season in Makkah, Saudi Arabia.

OBJECTIVE: To determine the incidence and type of RTI-causing bacteria and viruses during a period of epidemic infections. METHOD: A total of 395 sputum specimens and 761 throat swabs were collected during the 1991 and 1992 pilgrimage seasons (Haj to Makkah Al-Mukarama, Saudi Arabia) from patients referred to one hospital and three dispensaries with symptoms of respiratory tract infections. All 761 throat swabs of both Haj seasons were also screened for the presence of viral pathogens with monoclonal antibodies specific for 7 viruses known to cause respiratory infections. RESULTS: Bacterial pathogens were detected in 118 (29.9%) specimens. During the 1991 Haj season Haemophilus influenzae was the most frequent bacterial pathogen detected (10%), followed by Klebsiella pneumoniae (5.2%), Streptococcus pneumoniae (4.8%), Staphylococcus aureus (3.8%) and Streptococcus pyogenes (2.4%). In the 1992 Haj season Klebsiella pneumoniae was predominant (15.1%), followed by Haemophilus influenzae and Streptococcus pneumoniae (12.3%). Screening of all sputum specimens for acid-fast bacteria showed that the overall incidence rate of tuberculosis was 1%. Cultures from the 761 throat swabs were largely negative for bacteria except for Streptococcus pyogenes isolated from 7 patients. Viruses were detected in 148 (19.5%) specimens with influenza A and adenovirus being the most common viruses. CONCLUSION: The pattern of virus prevalence in the 1991 and 1992 pilgrimage seasons was identical: influenza A and adenovirus predominated. Thus these two viruses should be targeted in future prophylactic measures.

Antibodies, Monoclonal↗

PubMed1997

Renocolic fistula as a complication to xanthogranulomatous pyelonephritis.

Four patients with xanthogranulomatous pyelonephritis were found to have renocolic fistulae. Coincidentally, the left kidney was involved in all four cases. All patients presented with renal mass. Two cases have had coexistent renal stones, one of them presented with massive upper gastrointestinal bleeding as a result of portal hypertension. Another patient had a history of Schistosomiasis. In none of the patients was the renal condition confidently diagnosed preoperatively, nor was the colonic fistula suspected. In all four patients, nephrectomy was performed together with resection of the involved colon followed by a satisfactory recovery. The possibility of a colonic fistula should be kept in mind as a complication to this rare renal condition in spite of the absence of colonic symptoms and normal finding in barium enema studies.

Adult↗

PubMed1997

Risk factors of low dietary vitamin A intake among children in the Sudan.

We examined the determinants of dietary vitamin A intake among Sudanese children, information which is important for designing effective interventions based on the dietary approach. Children under the age of two years were at greater risk of consuming a diet low in vitamin A compared with children who were five years or older. Compared with children from relatively affluent households, those from poorer households were about twice as likely to consume low levels of carotenoid or preformed vitamin A. Low vitamin A intake was also significantly associated with lack of running water, a latrine, radio, or television in the household, and inversely associated with maternal or paternal illiteracy and with cleanliness of the child subjectively assessed by the interviewer. As expected, breastfed children in the first two years of life were likely to consume lower levels of preformed vitamin A and carotenoid from food (excluding breast milk) compared with non-breastfed children. Low vitamin A intake was more prevalent in the dry months of the year. Efforts to increase accessibility to vitamin A containing food, combined with nutrition education campaigns and public health programmes directed at improving sanitation and reducing infection are necessary as part of the long-term solution to the problem of vitamin A deficiency.

Age Factors↗