AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.T...AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.The controls were patients referred to our department due to other nonesophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology.In the ESCC patients,samples were taken from normal mucosa(56 mucosa samples) and from the tumor(56 tumor samples).Tissue samples from the controls were taken from normal mucosa of the middle esophagus(35 control samples).Quantitative determination of DNA was carried out using a spectrophotometric method.Genomic DNA was isolated using the QIAamp DNA Midi Kit.HPV infection was identified following PCR amplification of the HPV gene sequence,using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV.The sequencing results were computationally analyzed using the basic local alignment search tool database.RESULTS:In tumor samples,HPV DNA was identified in 28 of 56 patients(50%).High risk HPV phenotypes(16 or/and 18) were found in 5 of 56 patients(8.9%),low risk in 19 of 56 patients(33.9%) and other types of HPV(37,81,97,CP6108) in 4 of 56 patients(7.1%).In mucosa samples,HPV DNA was isolated in 21 of 56 patients(37.5%).High risk HPV DNA was confirmed in 3 of 56 patients(5.3%),low risk HPV DNA in 12 of 56 patients(21.4%),and other types of HPV in 6 of 56 patients(10.7%).In control samples,HPV DNA was identified in 4 of 35 patients(11.4%) with no high risk HPV.The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56(50%) vs 4 of 35(11.4%),P < 0.001].In esophageal cancer patients,both in tumor and mucosa samples,the predominant HPV phenotypes were low risk HPV,isolated 4 times more frequently than high risk phenotypes [19 of 56(33.9%) vs 5 of 56(8.9%),P < 0.001].A higher prevalence of HPV was identified in female patients(71.4% vs 46.9%展开更多
The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining ro...The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining roles for Wnt signaling in skeletal development during the 1990s, interest in the pathway rose exponentially when three key papers were published in 2001-2002. One report found that loss of the Wnt co-receptor, Low-density lipoprotein related protein-5 （LRPS）, was the underlying genetic cause of the syndrome Osteoporosis pseudoglioma （OPPG）. OPPG is characterized by early-onset osteoporosis causing increased susceptibility to debilitating fractures. Shortly thereafter, two groups reported that individuals carrying a specific point mutation in LRP5 （G171V） develop high-bone mass. Subsequent to this, the causative mechanisms for these observations heightened the need to understand the mechanisms by which Wnt signaling controlled bone development and homeostasis and encouraged significant investment from biotechnology and pharmaceutical companies to develop methods to activate Wnt signaling to increase bone mass to treat osteoporosis and other bone disease. In this review, we will briefly summarize the cellular mechanisms underlying Wnt signaling and discuss the observations related to OPPG and the high-bone mass disorders that heightened the appreciation of the role of Wnt signaling in normal bone development and homeostasis. We will then present a comprehensive overview of the core components of the pathway with an emphasis on the phenotypes associated with mice carrying genetically engineered mutations in these genes and clinical observations that further link alterations in the pathway to changes in human bone.展开更多
Crohn’s disease is a chronic inflammatory disease process involving different sites in the gastrointestinal tract. Occasionally, so-called metastatic disease occurs in extra-intestinal sites. Granulomatous...Crohn’s disease is a chronic inflammatory disease process involving different sites in the gastrointestinal tract. Occasionally, so-called metastatic disease occurs in extra-intestinal sites. Granulomatous inflammation may be detected in endoscopic biopsies or resected tissues. Genetic, epigenetic and environmental factors appear to play a role. Multiple susceptibility genes have been described in both familial and non-familial forms while the disease is phenotypically heterogeneous with a female predominance. The disorder occurs over a broad age spectrum, from early childhood to late adulthood. More than 80% are diagnosed before age 40 years usually with terminal ileal and colonic involvement. Pediatric-onset disease is more severe and more extensive, usually with a higher chance of upper gastrointestinal tract disease, compared to adult-onset disease. Long-term studies have shown that the disorder may evolve with time into more complex disease with stricture formation and penetrating disease complications (i.e., fistula, abscess). Although prolonged remission may occur, discrete periods of symptomatic disease may re-appear over many decades suggesting recurrence or re-activation of this inflammatory process. Eventual development of a cure will likely depend on identification of an etiologic cause and a fundamental understanding of its pathogenesis. Until now, treatment has focused on removing risk factors, particularly cigarette smoking, and improving symptoms. In clinical trials, clinical remission is largely defined as improved numerical and endoscopic indices for “mucosal healing”. “Deep remission” is a conceptual, more “extended” goal that may or may not alter the long-term natural history of the disease in selected patients, albeit at a significant risk for treatment complications, including serious and unusual opportunistic infections.展开更多
Multiple sclerosis is a chronic autoimmune disease of the central nervous system.It is the main cause of non-traumatic neurological disability in young adults.Multiple sclerosis mostly affects people aged 20–50 years...Multiple sclerosis is a chronic autoimmune disease of the central nervous system.It is the main cause of non-traumatic neurological disability in young adults.Multiple sclerosis mostly affects people aged 20–50 years;however,it can occur in young children and much older adults.Factors identified in the distribution of MS include age,gender,genetics,environment,and ethnic background.Multiple sclerosis is usually associated with progressive degrees of disability.The disease involves demyelination of axons of the central nervous system and causes brain and spinal cord neuronal loss and atrophy.Diagnosing multiple sclerosis is based on a patient’s medical history including symptoms,physical examination,and various tests such as magnetic resonance imaging,cerebrospinal fluid and blood tests,and electrophysiology.The disease course of multiple sclerosis is not well correlated with the biomarkers presently used in clinical practice.Blood-derived biomarkers that can detect and distinguish the different phenotypes in multiple sclerosis may be advantageous in personalized treatment with disease-modifying drugs and to predict response to treatment.The studies reviewed have shown that the expression levels of a large number of miRNAs in peripheral blood,serum,exosomes isolated from serum,and cerebrospinal fluid are altered in multiple sclerosis and can distinguish the disease phenotypes from each other.Further studies are warranted to independently validate these findings so that individual or pairs of miRNAs in serum or cerebrospinal fluid can be used as potential diagnostic markers for adult and pediatric multiple sclerosis and for monitoring disease progression and response to therapy.展开更多
A novel knottedl-like homeobox （knox） gene, Pttknl （Populus tremulaxtremuloides knottedl）, isolated from the cambial region of hybrid aspen, was introduced into Petunia hybrida Vilm. using the leafdisc method medi...A novel knottedl-like homeobox （knox） gene, Pttknl （Populus tremulaxtremuloides knottedl）, isolated from the cambial region of hybrid aspen, was introduced into Petunia hybrida Vilm. using the leafdisc method mediated by Agrobacterium. A series of novel phenotypes was observed in transgenic petunia plants, including the formation of ectopic spikes on the adaxial surface of corollas and small petals on the abaxial surface of corollas, fusion of floral organs, shortening of corolla midribs, the formation of tumor-like knots along the midrib on the abaxial surface and serrated lobs of corolla margins, and alterations in petal color; except for changes in the leaves and plant architecture, RT-PCR showed that the Pttknl gene was expressed in the leaves of different petunia transgenic plants, whereas no signal was detected in wild-type plants. The possible function of Pttknl in leaf and flower development is discussed.展开更多
基金Supported by Medical University of Lublin,Scientific Research Grant
文摘AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.The controls were patients referred to our department due to other nonesophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology.In the ESCC patients,samples were taken from normal mucosa(56 mucosa samples) and from the tumor(56 tumor samples).Tissue samples from the controls were taken from normal mucosa of the middle esophagus(35 control samples).Quantitative determination of DNA was carried out using a spectrophotometric method.Genomic DNA was isolated using the QIAamp DNA Midi Kit.HPV infection was identified following PCR amplification of the HPV gene sequence,using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV.The sequencing results were computationally analyzed using the basic local alignment search tool database.RESULTS:In tumor samples,HPV DNA was identified in 28 of 56 patients(50%).High risk HPV phenotypes(16 or/and 18) were found in 5 of 56 patients(8.9%),low risk in 19 of 56 patients(33.9%) and other types of HPV(37,81,97,CP6108) in 4 of 56 patients(7.1%).In mucosa samples,HPV DNA was isolated in 21 of 56 patients(37.5%).High risk HPV DNA was confirmed in 3 of 56 patients(5.3%),low risk HPV DNA in 12 of 56 patients(21.4%),and other types of HPV in 6 of 56 patients(10.7%).In control samples,HPV DNA was identified in 4 of 35 patients(11.4%) with no high risk HPV.The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56(50%) vs 4 of 35(11.4%),P < 0.001].In esophageal cancer patients,both in tumor and mucosa samples,the predominant HPV phenotypes were low risk HPV,isolated 4 times more frequently than high risk phenotypes [19 of 56(33.9%) vs 5 of 56(8.9%),P < 0.001].A higher prevalence of HPV was identified in female patients(71.4% vs 46.9%
基金supported by NIH grant AR053293the Van Andel Research Institutesupported by the Van Andel Institute Graduate School
文摘The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining roles for Wnt signaling in skeletal development during the 1990s, interest in the pathway rose exponentially when three key papers were published in 2001-2002. One report found that loss of the Wnt co-receptor, Low-density lipoprotein related protein-5 （LRPS）, was the underlying genetic cause of the syndrome Osteoporosis pseudoglioma （OPPG）. OPPG is characterized by early-onset osteoporosis causing increased susceptibility to debilitating fractures. Shortly thereafter, two groups reported that individuals carrying a specific point mutation in LRP5 （G171V） develop high-bone mass. Subsequent to this, the causative mechanisms for these observations heightened the need to understand the mechanisms by which Wnt signaling controlled bone development and homeostasis and encouraged significant investment from biotechnology and pharmaceutical companies to develop methods to activate Wnt signaling to increase bone mass to treat osteoporosis and other bone disease. In this review, we will briefly summarize the cellular mechanisms underlying Wnt signaling and discuss the observations related to OPPG and the high-bone mass disorders that heightened the appreciation of the role of Wnt signaling in normal bone development and homeostasis. We will then present a comprehensive overview of the core components of the pathway with an emphasis on the phenotypes associated with mice carrying genetically engineered mutations in these genes and clinical observations that further link alterations in the pathway to changes in human bone.
文摘Crohn’s disease is a chronic inflammatory disease process involving different sites in the gastrointestinal tract. Occasionally, so-called metastatic disease occurs in extra-intestinal sites. Granulomatous inflammation may be detected in endoscopic biopsies or resected tissues. Genetic, epigenetic and environmental factors appear to play a role. Multiple susceptibility genes have been described in both familial and non-familial forms while the disease is phenotypically heterogeneous with a female predominance. The disorder occurs over a broad age spectrum, from early childhood to late adulthood. More than 80% are diagnosed before age 40 years usually with terminal ileal and colonic involvement. Pediatric-onset disease is more severe and more extensive, usually with a higher chance of upper gastrointestinal tract disease, compared to adult-onset disease. Long-term studies have shown that the disorder may evolve with time into more complex disease with stricture formation and penetrating disease complications (i.e., fistula, abscess). Although prolonged remission may occur, discrete periods of symptomatic disease may re-appear over many decades suggesting recurrence or re-activation of this inflammatory process. Eventual development of a cure will likely depend on identification of an etiologic cause and a fundamental understanding of its pathogenesis. Until now, treatment has focused on removing risk factors, particularly cigarette smoking, and improving symptoms. In clinical trials, clinical remission is largely defined as improved numerical and endoscopic indices for “mucosal healing”. “Deep remission” is a conceptual, more “extended” goal that may or may not alter the long-term natural history of the disease in selected patients, albeit at a significant risk for treatment complications, including serious and unusual opportunistic infections.
文摘Multiple sclerosis is a chronic autoimmune disease of the central nervous system.It is the main cause of non-traumatic neurological disability in young adults.Multiple sclerosis mostly affects people aged 20–50 years;however,it can occur in young children and much older adults.Factors identified in the distribution of MS include age,gender,genetics,environment,and ethnic background.Multiple sclerosis is usually associated with progressive degrees of disability.The disease involves demyelination of axons of the central nervous system and causes brain and spinal cord neuronal loss and atrophy.Diagnosing multiple sclerosis is based on a patient’s medical history including symptoms,physical examination,and various tests such as magnetic resonance imaging,cerebrospinal fluid and blood tests,and electrophysiology.The disease course of multiple sclerosis is not well correlated with the biomarkers presently used in clinical practice.Blood-derived biomarkers that can detect and distinguish the different phenotypes in multiple sclerosis may be advantageous in personalized treatment with disease-modifying drugs and to predict response to treatment.The studies reviewed have shown that the expression levels of a large number of miRNAs in peripheral blood,serum,exosomes isolated from serum,and cerebrospinal fluid are altered in multiple sclerosis and can distinguish the disease phenotypes from each other.Further studies are warranted to independently validate these findings so that individual or pairs of miRNAs in serum or cerebrospinal fluid can be used as potential diagnostic markers for adult and pediatric multiple sclerosis and for monitoring disease progression and response to therapy.
基金Supported by the Gansu Provincial Natural Science Foundation of China （ZS021-A25-047-N） and Xi＇an Urban Rural Construction Committee.Acknowledgements The authors thank Dr. 0lof 0lsson （Goeteberg University, Goeteberg, Sweden） for providing the plasmid containing 35S：：Pttkn1.
文摘A novel knottedl-like homeobox （knox） gene, Pttknl （Populus tremulaxtremuloides knottedl）, isolated from the cambial region of hybrid aspen, was introduced into Petunia hybrida Vilm. using the leafdisc method mediated by Agrobacterium. A series of novel phenotypes was observed in transgenic petunia plants, including the formation of ectopic spikes on the adaxial surface of corollas and small petals on the abaxial surface of corollas, fusion of floral organs, shortening of corolla midribs, the formation of tumor-like knots along the midrib on the abaxial surface and serrated lobs of corolla margins, and alterations in petal color; except for changes in the leaves and plant architecture, RT-PCR showed that the Pttknl gene was expressed in the leaves of different petunia transgenic plants, whereas no signal was detected in wild-type plants. The possible function of Pttknl in leaf and flower development is discussed.
