scispace - formally typeset
Search or ask a question

Showing papers by "Johns Hopkins University published in 1995"


Journal ArticleDOI
TL;DR: Putnam as discussed by the authors showed that crucial factors such as social trust are eroding rapidly in the United States and offered some possible explanations for this erosion and concluded that the work needed to consider these possibilities more fully.
Abstract: After briefly explaining why social capital (civil society) is important to democracy, Putnam devotes the bulk of this chapter to demonstrating social capital’s decline in the United States across the last quarter century. (See Putnam 1995 for a similar but more detailed argument.) While he acknowledges that the significance of a few countertrends is difficult to assess without further study, Putnam concludes that crucial factors such as social trust are eroding rapidly in the United States. He offers some possible explanations for this erosion and concludes by outlining the work needed to consider these possibilities more fully.

11,187 citations


Journal ArticleDOI
TL;DR: Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells.
Abstract: Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. We show that both HIF-1 subunits are basic-helix-loop-helix proteins containing a PAS domain, defined by its presence in the Drosophila Per and Sim proteins and in the mammalian ARNT and AHR proteins. HIF-1 alpha is most closely related to Sim. HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. HIF-1 alpha and HIF-1 beta (ARNT) RNA and protein levels were induced in cells exposed to 1% O2 and decayed rapidly upon return of the cells to 20% O2, consistent with the role of HIF-1 as a mediator of transcriptional responses to hypoxia.

5,729 citations


Journal ArticleDOI
TL;DR: The results confirm the role of genitalHPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide and suggest that most genital HPVs are associated with cancer, at least occasionally.
Abstract: Background Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation Purpose Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types Methods More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity Results HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5% HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common There was significant geographic variation in the prevalence of some less common virus types A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors) Conclusions Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide They also suggest that most genital HPVs are associated with cancer, at least occasionally Implication The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs

3,272 citations


Journal ArticleDOI
02 Jun 1995-Science
TL;DR: Human colon cancer cell lines with high rates of microsatellite instability were found to harbor mutations in the type II TGF-beta receptor (RII) gene, which links DNA repair defects with a specific pathway of tumor progression.
Abstract: Transforming growth factor-beta (TGF-beta) is a potent inhibitor of epithelial cell growth. Human colon cancer cell lines with high rates of microsatellite instability were found to harbor mutations in the type II TGF-beta receptor (RII) gene. Eight such examples, due to three different mutations, were identified. The mutations were clustered within small repeated sequences in the RII gene, were accompanied by the absence of cell surface RII receptors, and were usually associated with small amounts of RII transcript. RII mutation, by inducing the escape of cells from TGF-beta-mediated growth control, links DNA repair defects with a specific pathway of tumor progression.

2,386 citations


Journal ArticleDOI
TL;DR: Hydroxyurea therapy can ameliorate the clinical course of sickle cell anemia in some adults with three or more painful crises per year and Maximal tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic effect.
Abstract: Background In a previous open-label study of hydroxyurea therapy, the synthesis of fetal hemoglobin increased in most patients with sickle cell anemia, with only mild myelotoxicity. By inhibiting sickling, increased levels of fetal hemoglobin might decrease the frequency of painful crises. Methods In a double-blind, randomized clinical trial, we tested the efficacy of hydroxyurea in reducing the frequency of painful crises in adults with a history of three or more such crises per year. The trial was stopped after a mean follow-up of 21 months. Results Among 148 men and 151 women studied at 21 clinics, the 152 patients assigned to hydroxyurea treatment had lower annual rates of crises than the 147 patients given placebo (median, 2.5 vs. 4.5 crises per year, P<0.001). The median times to the first crisis (3.0 vs. 1.5 months, P = 0.01) and the second crisis (8.8 vs. 4.6 months, P<0.001) were longer with hydroxyurea treatment. Fewer patients assigned to hydroxyurea had chest syndrome (25 vs. 51, P<0.001), and...

2,062 citations


Journal ArticleDOI
TL;DR: De novo methylation of the 5′ CpG island of p16 was found in approximately 20% of different primary neoplasms, but not in normal tissues, potentially representing a common pathway of tumour suppressor gene inactivation in human cancers.
Abstract: 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers

1,977 citations


Journal ArticleDOI
01 Jun 1995-Immunity
TL;DR: The data from both models established that TNF alpha and the 55 kDa TNF receptor are essential for protection against tuberculosis in mice, and for reactive nitrogen production by macrophages early in infection.

1,662 citations


Journal Article
TL;DR: Injection molding wherein a pair of separable mold plates are initially urged together and fluid plastic is injected into a mold cavity formed between the mold plates to form an article.
Abstract: Recently, there has been a rebirth of empiricism in the field of natural language processing. Manual encoding of linguistic information is being challenged by automated corpus-based learning as a method of providing a natural language processing system with linguistic knowledge. Although corpus-based approaches have been successful in many different areas of natural language processing, it is often the case that these methods capture the linguistic information they are modelling indirectly in large opaque tables of statistics. This can make it difficult to analyze, understand and improve the ability of these approaches to model underlying linguistic behavior. In this paper, we will describe a simple rule-based approach to automated learning of linguistic knowledge. This approach has been shown for a number of tasks to capture information in a clearer and more direct fashion without a compromise in performance. We present a detailed case study of this learning method applied to part-of-speech tagging.

1,563 citations


Journal ArticleDOI
TL;DR: Developing C‐terminal, antioligopeptide antibodies that were specific for each glutamate transporter subtype found that GLT‐1 immunoreactive protein was severely decreased in ALS, both in motor cortex (71% decrease compared with control) and in spinal cord.
Abstract: The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) is unknown, but defects in synaptosomal high-affinity glutamate transport have been observed. In experimental models, chronic loss of glutamate transport can produce a loss of motor neurons and, therefore, could contribute to the disease. With the recent cloning of three glutamate transporters, i.e., EAAC1, GLT-1, and GLAST, it has become possible to determine if the loss of glutamate transport in ALS is subtype specific. We developed C-terminal, antioligopeptide antibodies that were specific for each glutamate transporter. EAAC1 is selective for neurons, while GLT-1 and GLAST are selective for astroglia. Tissue from various brain regions of ALS patients and controls were examined by immunoblot or immunocytochemical methods for each transporter subtype. All tissue was matched for age and postmortem delay. GLT-1 immunoreactive protein was severely decreased in ALS, both in motor cortex (71% decrease compared with control) and in spinal cord. In approximately a quarter of the ALS motor cortex specimens, the loss of GLT-1 protein (90% decrease from control) was dramatic. By contrast, there was only a modest loss (20% decrease from control) of immunoreactive protein EAAC1 in ALS motor cortex, and there was no appreciable change in GLAST. The minor loss of EAAC1 could be secondary to loss of cortical motor neurons. As a comparison, glial fibrillary acidic protein, which is selectively localized to astroglia, was not changed in ALS motor cortex. Because there is no loss of astroglia in ALS, the dramatic abnormalities in GLT-1 could reflect a primary defect in GLT-1 protein, a secondary loss due to down regulation, or other toxic processes.

1,441 citations


Journal Article
TL;DR: In tumors, de novo methylation of the 5' CpG island is a frequent mode of inactivation of CDKN2/p16 and this alteration of p16 in colon cancer was particularly striking, since inactivation does not occur through homozygous deletion in this tumor type.
Abstract: The tumor suppressor gene CDKN2/p16/MTS1, located on chromosome 9p21, is frequently inactivated in many human cancers through homozygous deletion. Recently, we have reported another pathway of inactivation that involves loss of transcription associated with de novo methylation of a 5' CpG island of CDKN2/p16 in lung cancers, gliomas, and head and neck squamous cell carcinomas. We now show that this aberrant CpG island methylation also occurs frequently in cell lines of breast cancer (33%), prostate cancer (60%), renal cancer (23%), and colon cancer (92%) and is associated with loss of transcription. Primary tumors of the breast (31%) and colon (40%) also displayed de novo methylation of this CpG island. This alteration of p16 in colon cancer was particularly striking, since inactivation does not occur through homozygous deletion in this tumor type. Our data show that in tumors, de novo methylation of the 5' CpG island is a frequent mode of inactivation of CDKN2/p16 and also firmly demonstrate that CDKN2/p16 is one of the most frequently altered genes in human neoplasia.

1,399 citations



Journal Article
TL;DR: Results unambiguously establish p21 as a critical mediator of one well-documented p53 function and have important implications for understanding cell cycle checkpoints and the mechanism(s) through which p53 inhibits human neoplasia.
Abstract: DNA-damaging agents induce a p53-dependent G1 arrest that may be critical for p53-mediated tumor suppression. It has been suggested that p21WAF1/CIP1, a cdk inhibitory protein transcriptionally regulated by p53, is an effector of this arrest. To test this hypothesis, an isogenic set of human colon adenocarcinoma cell lines differing only in their p21 status was created. The parental cell line underwent the expected cell cycle changes upon induction of p53 expression by DNA damage, but the G1 arrest was completely abrogated in p21-deficient cells. These results unambiguously establish p21 as a critical mediator of one well-documented p53 function and have important implications for understanding cell cycle checkpoints and the mechanism(s) through which p53 inhibits human neoplasia.

Journal ArticleDOI
TL;DR: Cell culture models (e.g. 3T3-L1 cells) have been developed and transcription factors coordinate the expression of genes involved in creating and maintaining the adipocyte phenotype including the insulin-responsive glucose transporter (GLUT4), stearoyl CoA desaturase 1 (SCD1), and the fatty acid binding protein (422/aP2).
Abstract: Cell culture models (e.g. 3T3-L1 cells) have been developed for studying the process of adipocyte differentiation. Differentiation can be induced by adding insulin-like growth factor I, glucocorticoid, fatty acids, and an agent that increases intracellular cAMP level. The adipocyte differentiation program is regulated by transcriptional activators such as CCAAT/enhancer binding protein alpha (C/EBP alpha), peroxisomal proliferator activated receptor gamma 2 (PPAR gamma 2), fatty acid activated receptor (FAAR), and transcriptional repressors such as preadipocyte repressor element binding protein (PRE) and C/EBP undifferentiated protein (CUP). These transcription factors coordinate the expression of genes involved in creating and maintaining the adipocyte phenotype including the insulin-responsive glucose transporter (GLUT4), stearoyl CoA desaturase 1 (SCD1), and the fatty acid binding protein (422/aP2).

Journal ArticleDOI
TL;DR: The association between brain tumors and multiple colorectal adenomas can result from two distinct types of germ-line defects: mutation of the APC gene or mutation of a mismatch-repair gene.
Abstract: Background Turcot's syndrome is characterized clinically by the concurrence of a primary brain tumor and multiple colorectal adenomas. We attempted to define the syndrome at the molecular level. Methods Fourteen families with Turcot's syndrome identified in two registries and the family originally described by Turcot and colleagues were studied. Germ-line mutations in the adenomatous polyposis coli (APC) gene characteristic of familial adenomatous polyposis were evaluated, as well as DNA replication errors and germ-line mutations in nucleotide mismatch-repair genes characteristic of hereditary nonpolyposis colorectal cancer. In addition, a formal risk analysis for brain tumors in familial adenomatous polyposis was performed with a registry data base. Results Genetic abnormalities were identified in 13 of the 14 registry families. Germ-line APC mutations were detected in 10. The predominant brain tumor in these 10 families was medulloblastoma (11 of 14 patients, or 79 percent), and the relative risk of cer...

Journal ArticleDOI
TL;DR: A large International Restless Legs Syndrome (RLS) Study Group has been formed as discussed by the authors, which has taken upon itself the role of definig the clinical features of the RLS, including sleep disturbance, periodic limb movements in sleep and similar involuntary movements while awake, a normal neurological examination in the idiopathic from, a tendency for the symptoms to be worse in middle to older age, and a family history suggestive of an autosomal dominant mode of inheritance.
Abstract: A large International Restless Legs Syndrome (RLS) Study Group has been formed. As its first task, the group has taken upon itself the role of definig the clinical features of the RLS. As minimal criteria for diagnosis, the group proposes the following four features: (a) desire to move the extremities, often associated with paresthesias/dysesthesias; (b) motor restlessness; (c) worsening of symptoms at rest with at least temporary relief by activity, and (d) worsening of symptoms in the evening or night. Other features commonly seen in RLS include sleep disturbance, periodic limb movements in sleep and similar involuntary movements while awake, a normal neurological examination in the idiopathic from, a tendency for the symptoms to be worse in middle to older age, and, in some cases, a family history suggestive of an autosomal dominant mode of inheritance.

Journal ArticleDOI
Fumio Abe, H. Akimoto1, A. Akopian2, M. G. Albrow3  +443 moreInstitutions (34)
TL;DR: In this paper, the existence of the top quark was established using a data sample of collisions at the Fermilab National Ensemble (CDF) collected with the Collider Detector.
Abstract: We establish the existence of the top quark using a $67{\mathrm{pb}}^{\ensuremath{-}1}$ data sample of $\overline{p}p$ collisions at $\sqrt{s}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1.8\mathrm{TeV}$ collected with the Collider Detector at Fermilab (CDF). Employing techniques similar to those we previously published, we observe a signal consistent with $t\overline{t}$ decay to $\mathrm{WWb}\overline{b}$, but inconsistent with the background prediction by $4.8\ensuremath{\sigma}$. Additional evidence for the top quark is provided by a peak in the reconstructed mass distribution. We measure the top quark mass to be $176\ifmmode\pm\else\textpm\fi{}8(\mathrm{stat})\ifmmode\pm\else\textpm\fi{}10(\mathrm{syst})\mathrm{GeV}{/c}^{2}$, and the $t\overline{t}$ production cross section to be ${6.8}_{\ensuremath{-}2.4}^{+3.6}\mathrm{pb}$.


Book ChapterDOI
TL;DR: This chapter summarizes the experimental information on protein energetics and investigates the correlation between thermodynamic and structural characteristics of protein, including the water-ASA of various groups in the native and unfolded states, the number of hydrogen bonds, and the extent of van der Waals contacts in thenative state.
Abstract: Publisher Summary This chapter summarizes the experimental information on protein energetics. This field is developing fast and the concept of the energetics of protein structure has changed considerably during the past few years based on new findings. The proteins which are presented in the chapter are selected from a large number of proteins for which the thermodynamics of unfolding are studied in laboratory. The analysis of protein energetics presented in this chapter is based on several assumptions: (1) protein groups contribute additively, and proportionally as their surfaces, to the overall thermodynamic effects of unfolding; (2) the protein interior closely resembles an organic crystal in the way groups are packed and the energetics of the interactions among these groups are similar to those in the organic crystals; and (3) under certain conditions the denatured protein can be regarded as unfolded. The main criteria in choosing these proteins have been the reversibility of the denaturation process modeling unfolding, the completeness of this unfolding, the reliability of thermodynamic data on this process, and the resolution of the three dimensional structure of the given protein. The latter is important to investigate the correlation between thermodynamic and structural characteristics of protein, including the water-ASA of various groups in the native and unfolded states, the number of hydrogen bonds, and the extent of van der Waals contacts in the native state.

Journal ArticleDOI
21 Apr 1995-Cell
TL;DR: It is found that UBC4 and at least one other ubiquitin-conjugating enzyme can support cyclin B ubiquitination and suggested that APC functions as a regulated ubiquitIn-protein ligase that targets cyclin A for destruction in mitosis.

Journal ArticleDOI
TL;DR: Multivariate analyses indicated the strongest predictors of long-term survival were diploid tumor DNA content, tumor diameter < 3 cm, negative nodal status, negative resection margins, and decade of resection.
Abstract: OBJECTIVE: This single-institution study examined the outcome after pancreaticoduodenectomy in patients with adenocarcinoma of the head of the pancreas. SUMMARY OF BACKGROUND DATA: In recent years, pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas has been associated with decreased morbidity and mortality and, in some centers, 5-year survival rates in excess of 20%. METHODS: Two hundred one patients with pathologically verified adenocarcinoma of the head of the pancreas undergoing pancreaticoduodenectomy at The Johns Hopkins Hospital between 1970 and 1994 were analyzed (the last 100 resections were performed between March 1991 and April 1994). This is the largest single-institution experience reported to date. RESULTS: The overall postoperative in-hospital mortality rate was 5%, but has been 0.7% for the last 149 patients. The actuarial 5-year survival for all 201 patients was 21%, with a median survival of 15.5 months. There were 11 5-year survivors. Patients resected with negative margins (curative resections: n = 143) had an actuarial 5-year survival rate of 26%, with a median survival of 18 months, whereas those with positive margins (palliative resections; n = 58) fared significantly worse, with an actuarial 5-year survival rate of 8% and a median survival of 10 months (p < 0.0001). Survival has improved significantly from decade to decade (p < 0.002), with the 3-year actuarial survival of 14% in the 1970s, 21% in the 1980s, and 36% in the 1990s. Factors significantly favoring long-term survival by univariate analyses included tumor diameter < 3 cm, negative nodal status, diploid tumor DNA content, tumor S phase fraction < 18%, pylorus-preserving resection, < 800 mL intraoperative blood loss, < 2 units of blood transfused, negative resection margins, and use of postoperative adjuvant chemotherapy and radiation therapy. Multivariate analyses indicated the strongest predictors of long-term survival were diploid tumor DNA content, tumor diameter < 3 cm, negative nodal status, negative resection margins, and decade of resection. CONCLUSIONS: The survival of patients with pancreatic adenocarcinoma treated by pancreaticoduodenectomy is improving. Aspects of tumor biology, such as DNA content, tumor diameter, nodal status and margin status, are the strongest predictors of outcome.

Journal Article
TL;DR: The technique of laparoscopic live donor nephrectomy has resulted in improved postoperative recovery and shorter convalescence, with no effect on recipient renal function.
Abstract: A laparoscopic live-donor nephrectomy was performed on a 40-year-old man. The kidney was removed intact via a 9-cm infraumbilical midline incision. Warm ischemia was limited to less than 5 min. Immediately upon revascularization, the allograft produced urine. By the second postoperative day, the recipient's serum creatinine had decreased to 0.7 mg/dl. The donor's postoperative course was uneventful. He experienced minimal discomfort and was discharged home on the first postoperative day. We conclude that laparoscopic donor nephrectomy is feasible. It can be performed without apparent deleterious effects to either the donor or the recipient. The limited discomfort and rapid convalescence enjoyed by our patient indicate that this technique may prove to be advantageous.

Journal ArticleDOI
TL;DR: Pneumonia has been recognized as a common and potentially lethal condition for nearly two centuries as discussed by the authors, and community-acquired pneumonia (as distinguished from that acquired nosocomially or in a nursing home) continues to be a very serious illness.
Abstract: Pneumonia has been recognized as a common and potentially lethal condition for nearly two centuries. Comprehensive studies of the disease in the pre-antibiotic era showed mortality rates of about 1 per 1000 per year; over 80 percent of the cases were due to Streptococcus pneumoniae, and mortality rates were generally reported at 20 to 40 percent.1,2 Community-acquired pneumonia (as distinguished from that acquired nosocomially or in a nursing home) continues to be a common and serious illness. Current estimates for the United States are 4 million cases annually, an attack rate of 12 per 1000 adults per year, about . . .

Journal ArticleDOI
TL;DR: Chronic gastrointestinal symptoms and histological changes of the esophagus unresponsive to standard treatments for gastroesophageal reflux were improved by the use of elemental formulas.

Journal ArticleDOI
TL;DR: Research review has long been one of the most important scholarly activities in all branches of science and there is a need for reviewers to carefully consider the evidence and to put forth conclusions or hypotheses about where the weight of the evidence lies.


Journal Article
TL;DR: The data demonstrate that frequent loss of E-cad expression in human breast and prostate carcinomas results from hypermethylation of the E- cad promoter region.
Abstract: Expression of the Ca2+-dependent, homotypic cell:cell adhesion molecule, E-cadherin (E-cad), suppresses tumor cell invasion and metastasis in experimental tumor models. Decreased E-cad expression is common in poorly differentiated, advanced-stage carcinomas. These data implicate E-cad as an “invasion suppressor” gene. The mechanism by which E-cad is silenced in advanced stage carcinomas is unclear. In this report, we show that: (a) the 5′ CpG island of E-cad is densely methylated in E-cad-negative breast and prostate carcinoma cell lines and primary breast carcinoma tissue but is unmethylated in normal breast tissue; (b) treatment with the demethylating agent, 5-aza-2′-deoxycytidine, partially restores E-cad RNA and protein levels in E-cad-negative breast and prostate carcinoma cell lines; and (c) an E-cad promoter/CAT construct is expressed in both E-cad-positive and -negative breast and prostate carcinoma cell lines, indicating that these cells have the active transcriptional machinery necessary for E-cad gene expression. Our data demonstrate that frequent loss of E-cad expression in human breast and prostate carcinomas results from hypermethylation of the E-cad promoter region.

Journal ArticleDOI
TL;DR: The results demonstrate that tumours can acquire somatic mutations that presumably do not directly affect cell growth but result only in genetic instability and suggest that many sporadic tumours with microsatellite instability have alterations in genes other than the four now known to participate in MMR.
Abstract: Microsatellite instability has been observed in both sporadic and hereditary forms of colorectal cancer. In the hereditary form, this instability is generally due to germline mutations in mismatch repair (MMR) genes. However, only one in ten patients with sporadic tumours exhibiting microsatellite instability had a detectable germline mutation. Moreover, only three of seven sporadic tumour cell lines with microsatellite instability had mutations in a MMR gene, and these mutations could occur somatically. These results demonstrate that tumours can acquire somatic mutations that presumably do not directly affect cell growth but result only in genetic instability. They also suggest that many sporadic tumours with microsatellite instability have alterations in genes other than the four now known to participate in MMR.

Journal Article
TL;DR: The TGF beta type II receptor was found to be mutated within a polyadenine tract in 100 of 111 colorectal cancers with microsatellite instability, supporting the idea that RII behaves like a tumor suppressor during CR cancer development and is a critical target of inactivation in mismatch repair-deficient tumors.
Abstract: The TGF beta type II receptor (RII) was found to be mutated within a polyadenine tract in 100 of 111 (90%) colorectal cancers with microsatellite instability Other polyadenine tracts of similar length were mutated in these samples but not as frequently as RII In most cases, the polyadenine tract mutations affected both alleles of RII, and in four tumors heterozygous for the polyadenine mutations, three had additional mutations that were expected to inactivate the other RII allele These genetic data support the idea that RII behaves like a tumor suppressor during CR cancer development and is a critical target of inactivation in mismatch repair-deficient tumors

Journal ArticleDOI
TL;DR: It is demonstrated that a trait for an elevated level of serum total IgE is coinherited with a traits for bronchial hyperresponsiveness and that a gene governing bronchiahyperresponsiveness is located near a major locus that regulates serum IgE levels on chromosome 5q.
Abstract: Background Bronchial hyperresponsiveness, a risk factor for asthma, consists of a heightened bronchoconstrictor response to a variety of stimuli. The condition has a heritable component and is closely related to serum IgE levels and airway inflammation. The basis for these relations is unknown, as is the mechanism of genetic susceptibility to bronchial hyperresponsiveness. We attempted to define the interrelation between atopy and bronchial hyperresponsiveness and to investigate the chromosomal location of this component of asthma. Methods We studied 303 children and grandchildren of 84 probands with asthma selected from a homogeneous population in the Netherlands. Ventilatory function, bronchial responsiveness to histamine, and serum total IgE were measured. The association between the last two variables was evaluated. Using analyses involving pairs of siblings, we tested for linkage between bronchial hyperresponsiveness and genetic markers on chromosome 5q31-q33, previously shown to be linked to a genet...

Journal ArticleDOI
12 May 1995-Science
TL;DR: A gene from human chromosome 11p11.2 was isolated and was shown to suppress metastasis when introduced into rat AT6.1 prostate cancer cells.
Abstract: A gene from human chromosome 11p112 was isolated and was shown to suppress metastasis when introduced into rat AT61 prostate cancer cells Expression of this gene, designated KAI1, was reduced in human cell lines derived from metastatic prostate tumors KAI1 specifies a protein of 267 amino acids, with four hydrophobic and presumably transmembrane domains and one large extracellular hydrophilic domain with three potential N-glycosylation sites KAI1 is evolutionarily conserved, is expressed in many human tissues, and encodes a member of a structurally distinct family of leukocyte surface glycoproteins Decreased expression of this gene may be involved in the malignant progression of prostate and other cancers