Effects of mast cell-macrophage interactions on the production of collagenolytic enzymes by metastatic tumor cells and tumor-derived and stromal fibroblasts

Histological examination of the metastatic rat mammary adenocarcinoma line MTLn3 showed that macrophages and mast cells were frequently localized at the tumor periphery in the stromal tissues adjacent to the zones of tumor invasion. The interactions of these host cells with tumor cells and tumor-associated fibroblasts could be important in stimulating the production of extracellular matrix-degrading enzymes that facilitate tumor invasion and metastatic spread. Therefore, we examined the effects of isolated, activated macrophages and mast cells on the secretion of collagenolytic activities by normal fibroblasts, metastatic mammary adenocarcinoma cells and tumor-associated fibroblasts. Medium from activated macrophages or degranulated mast cells stimulated significant increases in production of collagenolytic activities by normal and tumor-associated fibroblasts and MTLn3 tumor cells. Medium from activated macrophages that had been pretreated with medium from degranulated mast cells, however, were less stimulatory to fibroblasts and tumor cell production of collagenolytic activities than medium from degranulated mast cells alone. We also examined the effects of two cytokines, interleukin-1 and tumor necrosis factor-a on activated macrophage- and degranulated mast cell-stimulation of fibroblast and tumor cell collagenolytic activities. The two cytokines alone or in combination stimulated increased production of collagenolytic activities by fibroblasts and tumor cells. Addition of the cytokines to degranulated mast cell products resulted in secretion of higher collagenolytic enzyme activities by normal fibroblasts (but not by tumor-derived fibroblasts or tumor cells) than with degranulated mast cell product-treatment of either target cell alone. Cytokines used in combination with macrophage-conditioned medium were less effective in stimulating fibroblast and tumor cell collagenase activities than cytokines alone. Thus normal infiltrating host cells such as macrophages and mast cells can have profound effects on the production of degradative enzymes by tumor cells and tumor-associated stromal fibroblasts.     

Interaction of a 60-kilodalton D-mannose-containing salivary glycoprotein with type 1 fimbriae of Escherichia coli.

A 60-kilodalton glycoprotein previously isolated and purified from human saliva (J. B. Babu, E. H. Beachey, D. L. Hasty, and W. A. Simpson, Infect. Immun. 51: 405-413, 1986) was found to interact with type 1 fimbriae and prevent adhesion of type 1 fimbriated Escherichia coli to animal cells in a D-mannose-sensitive manner. Purified salivary glycoprotein agglutinated type 1 fimbriated E. coli and, at subagglutinating concentrations, blocked the ability of type 1 fimbriated E. coli to attach to human buccal epithelial cells or agglutinate guinea pig erythrocytes. Both interactions were inhibited by alpha-methyl-D-mannoside but not by alpha-methyl-D-glucoside. Complexing of the glycoprotein to type 1 fimbriae was demonstrated by molecular sieve chromatography and modified Western blots. When mixed with type 1 fimbriae, the radiolabeled salivary glycoprotein coeluted with type 1 fimbriae from a column of Sepharose 4B. When blotted from a sodium dodecyl sulfate gel to nitrocellulose sheets, the glycoprotein interacted directly with type 1 fimbriae applied to the blots. Both of the latter interactions also were blocked by alpha-methyl-D-mannoside but not by alpha-methyl-D-glucoside. Chemical modification of the glycoprotein with sodium metaperiodate abolished its ability to interact with isolated type 1 fimbriae or type 1 fimbriated E. coli. These results suggest that the carbohydrate moiety of the 60-kilodalton glycoprotein serves as a receptor for type 1 fimbriae in the oral cavity, and we postulate that the interaction may cause agglutination and early removal of E. coli, thereby preventing colonization by these organisms of oropharyngeal mucosae and dental tissues.     

Collagens in scar carcinoma of the lung.

Immunohistopathologic and biochemical studies of different collagen types extracted from human scar carcinoma of the lungs have been carried out for definition and evaluation of which types of collagen are involved in the scarring mechanism of such tumors. Tumor homogenates treated with 0.5 M acetic acid and followed by limited proteolysis with pepsin and then by fractional salt precipitation, demonstrated that Type I collagen constitutes the major collagenous component in addition to a significant increase in Type V collagen extracted from human scar carcinoma of the lung. However, when normal membranoalveolar peripheral lung tissues were processed under the same experimental conditions, Type III and IV collagens were relatively higher. Immunohistochemical studies were carried out, and the results confirmed the data above. Furthermore, these studies demonstrated a relative localized increase in Type III collagen in the area surrounding the tumor acini, which suggested that these areas are of active and recent scar formation. This supports the current concept of the scar origin as a desmoplastic reaction of the host tissues toward the neoplastic cell growth.     

Psychosocial and economic profile of a sample of families with thalassaemic children in Lebanon.

Thalassaemia major is a relatively common disease in Lebanon. This study of 41 families with 54 patients attending the American University of Beirut Medical Center was conducted to define some aspects of the disease in Lebanon and to assess the attitudes of affected families on relevant psychosocial and economic issues. We conclude that because of the high frequency of consanguineous marriage, thalassaemia major is more common in Lebanon than might be expected on the basis of the incidence of the trait. Most patients are diagnosed early in life, but their treatment is generally far from adequate; securing desferrioxamine and paying for follow up visits to the doctor seem to be the most important financial burdens. The general population of the country is not properly informed yet and about 70% of the families had not heard about the disease before having an affected child. The inherited nature of the disease is not clear in the minds of a high percentage of the families, and in about 30% of cases the family had not been told about the advisability of screening to detect heterozygotes. The great majority of families favour a preventive approach to thalassaemia, based on heterozygote screening and the possibility of prenatal diagnosis.     

改良式剖宫产术50例临床分析

探讨改良式剖宫产术的临床价值。方法：采用香港周杰医师１９９１年创立的一套改式剖宫产术对５０例产妇进行手术并与同期腹部横切口传统剖宫产术进行比较。结果：改良式剖宫产术所用时间短,术中出血小,术后排气暗暗科痛轻、产褥病发生率低。住院时间短,与对照组比较有明显差异。     

Prediction of post-cardiopulmonary bypass cardiac output by venous oximetry

The present study evaluates two equations for predicting the post-cardiopulmonary bypass cardiac output (CO) in 10 patients undergoing coronary artery bypass grafting. One equation is based on the relationship of CO with mixed venous oxygen saturation (SVO 2), while the second equation is based on the relationship with oxygen extraction (1 - SVO 2). Each patient served as his own control. During bypass, when the patients were normothermic and perfused with a pump flow of 2.4 L/min/m 2, the SVO 2 was monitored by an in-line Bentley oxystat Meter. Just before termination of bypass, the pump flow was decreased to 0.4 L/min/m 2 and the left atrial pressure was increased to 10-15 mmHg; the resulting SVO 2 was recorded. The post-bypass CO was predicted in every patient by the two equations. Immediately after weaning from bypass, the cardiac output was measured by thermodilution. The thermodilutional CO measurement was correlated with the CO predicted by the two equations. Correlation analysis suggests that CO prediction is more accurate and approaches the 1:1 ratio when the calculation of predicted CO is based on the relationship between cardiac output and oxygen extraction.     

Human papillomavirus subtype 16 is common in Pakistani women with cervical carcinoma.

INTRODUCTION: Human papillomavirus (HPV) is recognized as a major causative agent for cervical carcinomas. Based on their oncogenic potential, HPV subtypes have been divided into high- and low-risk. In Pakistan, screening for HPV in female patients is not commonly practiced, and as a consequence, the degree of HPV prevalence and its correlation with cervical cancer is unknown. OBJECTIVE: In this study, we have attempted to estimate the prevalence of HPV infection, and also the HPV subtype profile, among Pakistani women with cervical cancer from varied geographical, racial, and social backgrounds within Pakistan. METHODOLOGY: Women visiting two tertiary care hospitals in Karachi, diagnosed with carcinoma of the cervix within the past 15 years, were analyzed for HPV subtypes in their cancer specimens. Retrospectively, 60 paraffin-embedded cervical cancer biopsies were examined for the presence of HPV DNA. After DNA extraction from these samples, polymerase chain reaction (PCR) was used to amplify the HPV L1 gene using the consensus (general) primers, and primers specific for subtypes 16 and 18. RESULTS: Of the 60 samples analyzed, only one sample was HPV negative; the rest of the samples were positive for the presence of HPV. Of the 59 HPV positive samples, 56 showed the presence of HPV16 and one sample was positive for HPV18; HPV subtype could not be determined in two samples. CONCLUSION: Our results show a strong relationship between HPV infection and cervical cancer among Pakistani women. These results underscore the need to implement regular HPV screening for Pakistani women. An early diagnosis of HPV infection will allow better health management to reduce the risk of developing cervical cancer.     

Molecularly imprinted ‘traps’ for sulfonylureas prepared using polymerisable ion pairs

A novel approach towards recognition of sulfonylureas based on a polymerisable ion pair is presented. A solution association constant >10⁵ M⁻¹ between the model target glibenclamide and 4-vinylbenzyltrimethylammonium methacrylate is measured, and the formation of 1 : 1 complexes verified. Subsequently prepared stoichiometrically imprinted polymers exhibit exceptionally high affinity and binding capacity for glibenclamide, owing to synergistic binding of both the neutral and deprotonated form of the drug by the ion pair monomer. The polymers are applied to the selective extraction of glibenclamide from blood serum samples, achieving recoveries of up to 98% and demonstrating excellent long-term stability, negating the need for regular sorbent regeneration.

Polymerisable ion pair captures both neutral and anionic form of acidic sulfonylurea drug in stoichiometrically imprinted polymer.     

Prevalence of peripheral neuropathy among type 2 diabetes mellitus patients in a rural health centre in South India

International Journal of Diabetes in Developing Countries - There is a huge burden of diabetes-related complications, both microvascular and macrovascular, in India. With the rising prevalence of...