Biomedical subjects

A Sonnenberg

Publications and source records attributed to A Sonnenberg.

At least 163 records · Page 9Linked to original sources

PubMed1996

Cleavage of the alpha6A subunit is essential for activation of the alpha6Abeta1 integrin by phorbol 12-myristate 13-acetate.

The alpha6 integrin subunit is proteolytically cleaved during biosynthesis in a covalently associated heavy and light chain. To examine the importance of cleavage for the function of the alpha6 subunit, we introduced mutations in the cDNA encoding the RKKR (876-879) sequence, the presumed cleavage site, in which either one or two basic residues were replaced by glycine. Wild-type and mutant alpha6A cDNAs (alpha6GKKR, alpha6RKKG and alpha6RGGR) were transfected into K562 cells. The mutant alpha6A integrin subunits were expressed in association with endogenous beta1, at levels comparable to that of the wild-type alpha6Abeta1. A single alpha6A polypeptide chain (150 kDa) was precipitated from surface-labeled alpha6GKKR, alpha6RKKG, and alpha6-RGGR transfectants, while the separate heavy (120 kDa) and light chains (31 or 30 kDa) were precipitated from the wild-type alpha6RKKR transfectant. Thus, a change in the RKKR sequence prevents cleavage of alpha6. After activation by the anti-beta1 stimulatory mAb TS2/16 both cleaved and uncleaved alpha6Abeta1 integrins bound and spread on laminin-1. Remarkably, the phorbol ester phorbol 12-myristate 13-acetate, which activates wild-type alpha6Abeta1 to bind to laminin-1, did not activate uncleaved alpha6Abeta1. We conclude that uncleaved alpha6Abeta1 is capable of ligand binding and transducing outside/in signals, like wild-type alpha6A-beta1. However, inside/out signaling is affected. It appears that cleavage of alpha6 is required to generate the proper conformation in alpha6 that enables affinity modulation of the alpha6A-beta1 receptor by phorbol 12-myristate 13-acetate.

Amino Acid Sequence↗

PubMed1996

Generalized atrophic benign epidermolysis bullosa. Either 180-kd bullous pemphigoid antigen or laminin-5 deficiency.

BACKGROUND: Generalized atrophic benign epidermolysis bullosa (GABEB) is a form of nonlethal junctional epidermolysis bullosa, clinically characterized by generalized blistering after birth, atrophic healing, and incomplete universal atrophic alopecia with onset in childhood. Recently, we discovered a deficiency of the 180-kd bullous pemphigoid antigen (BP180) and a reduced amount of BP180 messenger RNA in three patients with GABEB. It is not yet clear, however, whether GABEB is invariably caused by BP180 deficiency. RESULTS: We examined 18 patients with nonlethal junctional epidermolysis bullosa from unrelated families; nine of these individuals presented with the clinical characteristics of GABEB. Specimens of clinically normal skin obtained from the patients were stained by immunofluorescence with monoclonal antibodies to BP180 and laminin-5. The BP180 epitopes were not expressed in eight patients, all of whom were sharing the typical clinical features of GABEB. In one of the nine patients with GABEB, the BP180 level was sufficient, but the laminin-5 level was reduced. Among the nine patients with junctional epidermolysis bullosa without atrophic alopecia, laminin-5 level was not expressed in one patient, while in the other patients both antigens were normally expressed. CONCLUSIONS: Not all patients with GABEB are deficient in BP180, since some individuals with GABEB only exhibit reduction of the laminin-5 expression. The BP180 deficiency in the skin invariably seems to result in GABEB. Immunofluorescence analysis using monoclonal antibodies against BP180 (and laminin-5) may allow early subtyping, which is of prognostic significance, in children born with junctional epidermolysis bullosa.

Adolescent↗

PubMed1996

Hemidesmosomes: roles in adhesion, signaling and human diseases.

Our understanding of the role of hemidesmosomes in cell-substratum adhesion has greatly improved both as a result of targeted gene mutation experiments and by means of observations of several blistering disorders of the skin in which the absence or defects of hemidesmosomal proteins have been demonstrated. Functionally important domains within the proteins that constitute hemidesmosomes have recently been identified by transfection and mutagenesis studies. These multiprotein complexes appear not only to mediate cell adhesion, but also to transduce signals from the extracellular matrix to the cell interior that may profoundly modulate cell behavior.

Animals↗

PubMed1996

Epithelial detachment due to absence of hemidesmosomes in integrin beta 4 null mice.

Integrins are heterodimeric transmembrane glycoproteins which are engaged in a variety of cellular functions, such as adhesion, migration and differentiation1. The integrin alpha 6 beta 4 is expressed on squamous epithelia, on subsets of endothelial cells, immature thymocytes and on Schwann cells and fibroblasts in the peripheral nervous system. In stratified epithelia, alpha 6 beta 4 is concentrated in specialised adhesion structures, called hemidesmosomes, which are implicated in the stable attachment of the basal cells to the underlying basement membrane by connecting the intermediate filaments with the extracellular matrix. The nature of the interactions between the various hemidesmosomal proteins, that lead to the formation of hemidesmosome is poorly understood. To study the contribution of the integrin alpha 6 beta 4 in hemidesmosome formation and their anchoring properties, we inactivated the beta 4 gene in mice by targeted gene disruption. Homozygous beta 4 null mice died shortly after birth and displayed extensive detachment of the epidermis and other squamous epithelia. The dramatically reduced adhesive properties of the skin was accompanied by the absence of hemidesmosomes at the basal surface of keratinocytes. No evidence was found for impaired T-cell development, nor for defects in myelination in the peripheral nervous system.

Animals↗

PubMed1996

Comorbid occurrence of cholelithiasis and gastrointestinal cancer.

OBJECTIVE: To test whether gallstone disease represents a general risk factor for gastrointestinal cancer. METHODS: The comorbid occurrences of cholelithiasis or choledocholithiasis with cancers of the biliary tract, pancreas, small and large intestine were analysed in a population of 3.41 million military veterans who were discharged from VA hospitals distributed throughout the USA between 1981 and 1993. Comorbidity was calculated as the ratio between the observed and expected number of hospitalized veterans with cholelithiasis plus cancer. A 95% confidence interval was calculated based on the Poisson distribution of the observed number of patients with comorbidity. RESULTS: In cholelithiasis, the ratio of comorbid occurrence with biliary cancer was 4.59 (4.06-5.31). In choledocholithiasis, the ratio of comorbid occurrence with biliary cancer was 9.31 (7.20-11.84) and with pancreatic cancer 4.34 (3.80-4.94). These ratios remained significant when the analyses were confined to cholelithiasis or choledocholithiasis documented before the first diagnosis of cancer. The ratios of the comorbid occurrences between cholelithiasis and cancers of the small or large intestine were only significant when total comorbid occurrences were analysed, but vanished in the analysis restricted to cholelithiasis or choledocholithiasis documented before the first diagnosis of cancer. CONCLUSION: The occurrence of gallstones represents a risk factor for pancreaticobiliary cancer, but not cancers involving other parts of the gastrointestinal tract. This association appears particularly strong in patients with choledocholithiasis.

Cholelithiasis↗

PubMed1996

Deficiency of the integrin beta 4 subunit in junctional epidermolysis bullosa with pyloric atresia: consequences for hemidesmosome formation and adhesion properties.

Junctional epidermolysis bullosa (JEB) comprises a group of inherited autosomal recessive blistering disorders characterized by dermo-epidermal separation through the lamina lucida of the basement membrane. We identified a patient with JEB associated with pyloric atresia (PA), in whom the integrin beta 4 subunit was completely absent. At the ultrastructural level, the hemidesmosomes were reduced in number, appeared rudimentary and lacked a subbasal dense plate and frequently an inner attachment plaque. However, keratin filaments were still anchored to the cytoplasmic plaque of the hemidesmosome. Immunofluorescence analysis showed that the beta 4 subunit was absent in the skin of the PA-JEB patient, whereas the alpha 6 subunit appeared to be normally distributed along the basement membrane zone, as were the other hemidesmosomal components BP230, BP180 and HD1. Furthermore, the alpha 3 and beta 1 subunits were not only detected at the lateral membranes of basal cells in PA-JEB skin, as in normal skin, but also along the basement membrane zone. The few hemidesmosome-like structures found in cultured keratinocytes from the PA-JEB patient contained the hemidesmosomal components BP230, BP180 and HD1, but not the integrin alpha 6 subunit. Like alpha 3, this subunit was colocalized with vinculin in focal contacts at the ends of actin stress fibers. Immunoprecipitation analysis revealed that alpha 6 was associated with beta 1 on PA-JEB keratinocytes, whereas normal human keratinocytes (NHKs) exclusively express alpha 6 beta 4 on their cell surface. The initial adhesion of PA-JEB and normal keratinocytes to laminin-1 and laminin-5, both ligands for alpha 6 beta 1 and alpha 6 beta 4, was similar. In migration assays, the PA-JEB keratinocytes were more motile on laminin-5 than normal keratinocytes. Our observations indicate that the integrin alpha 6 beta 4 plays a crucial role in the proper assembly of hemidesmosomes and in the stabilization of the dermal-epidermal junction. The fragility of the skin and the blistering in this patient appear to have been due to the deficiency of the integrin beta 4 subunit, which results in the formation of too few and structurally abnormal hemidesmosomes.

Antigens, CD↗

PubMed1996

The prevalence of self-reported peptic ulcer in the United States.

OBJECTIVES: The purpose of this study was to draw a current picture of the sociodemographic characteristics of peptic ulcer in the United States. METHODS: During the National Health Interview Survey of 1989, a special questionnaire on digestive diseases was administered to 41,457 randomly selected individuals. Data were retrieved from public use tapes provided by the National Center for Health Statistics. Odds ratios were calculated by logistic regression after adjustment for sample weights in the survey. RESULTS: Of adult US residents, 10% reported having physician-diagnosed ulcer disease, and one third of these individuals reported having an ulcer in the past year. Old age, short education, low family income, being a veteran, and smoking acted as significant and independent risk factors. Gastric and duodenal ulcer occurred in both sexes equally often. Duodenal ulcer was more common in Whites than non-Whites, while gastric ulcer was more common in non-Whites. CONCLUSIONS: The age-related rise and socioeconomic gradients of peptic ulcer represent the historic scars of previous infection rates with Helicobacter pylori. The racial variations reflect different ages at the time of first infection; younger and older age at the acquisition of H. pylori appear to be associated with gastric and duodenal ulcer, respectively.

Adolescent↗

PubMed1996

Genomic organization of the mouse beta 1 gene: conservation of the beta 1D but not of the beta 1B and beta 1C integrin splice variants.

We have determined the genomic organization of the 3'-region of the murine beta 1 gene and cloned the murine beta 1D integrin splice variant. Overlapping genomic clones encompassing the region of the beta 1D-specific exons were isolated from a phage lambda FIXII library, mapped and partially sequenced. All of the exon-intron junctions identified in the murine beta 1 gene fit with the consensus splice donor and acceptor sequences and occur at the same positions as in their human counterparts. cDNA clones for the beta 1D integrin were isolated from a murine skeletal muscle library. The human and murine beta 1D sequences are conserved at the nucleotide (93%) and amino acid (100%) level, suggesting an important role of this muscle-specific variant throughout mammalian phylogenesis. In contrast, murine sequences for beta 1B are very different from human beta 1B at both the nucleotide as well as amino acid level. Moreover, no specific polyadenylation signal for the beta 1B variant could be identified in genomic clones, suggesting that this variant is not present in the mouse. Finally, we were not able to identify a murine beta 1C splice variant by sequencing analysis, Southern hybridization techniques or polymerase chain reaction of mRNA from platelets. These findings indicate that the beta 1B and beta 1C variants emerged relatively late in the phylogenesis of the beta 1 integrin family.

Animals↗

PubMed1996

Distribution of laminin variants and their integrin receptors in human secondary lymphoid tissue. Colocalization suggests that the alpha 6 beta 4-integrin is a receptor for laminin-5 in lymphoid follicles.

Laminins are a family of multifunctional basement membrane glycoproteins. Over the last years, many laminin isoforms have been characterized, which were shown to be composed of distinct combinations of variant alpha, beta and gamma chains. Some of these isoforms show remarkable tissue specificity, which suggests functional involvement in local processes. In this study the previously described mAb 4C7, which recognize epithelial basement membranes as well as endothelial basement membranes in lymphoid follicles, was identified as an anti-laminin-5 antibody. Using a set of mAbs against various variant laminin chains we established that specifically the gamma 2 chain of laminin-5 was confined to the endothelial basement membranes of vessels in lymphoid follicles, whereas other variant laminin chains were also expressed elsewhere in the lymphoid follicles, whereas other variant laminin chains were also expressed elsewhere in the lymphoid tissue. Additionally, the expression of the known integrin receptors of laminin-5 was also examined. The alpha 6 beta 4 integrin-receptor for laminin was found to be colocalized with the laminin-5 gamma 2 chain on the abluminal surface of endothelial cells, whereas the alpha 3 integrin chain could not be detected in lymphoid follicles. This finding suggests that the alpha 6 beta 4 integrin (and not the alpha 3 beta 1 integrin) serves as a laminin-5 receptor on endothelial cells in the follicular compartment of lymphoid tissue. Furthermore, alpha 6 beta 4 was also found in the same punctuated pattern on FDCs as laminin-5. The function of the laminin-alpha 6 beta 4 complex in this particular localisation is still obscure, but a role in the maintainance of the follicular compartment via hemidesmosome-like attachment sites is postulated.

Antibodies, Monoclonal↗

PubMed1996

Risk factors of colorectal cancer in inflammatory bowel disease.

BACKGROUND: It is unknown whether colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) behaves differently from regular CRC in patients without IBD. A case-control study was conducted to compare CRC in patients with and without underlying IBD. METHODS: The Department of Veterans Affairs (VA) maintains a computerized file of all hospital discharges among U.S. military veterans since 1970. This file accrues the data of 1 million hospital discharges per year. All patients with IBD and all patients with CRC who had been discharged from a VA hospital between 1981 and 1993 were selected. The influence of various risk factors on the occurrence of CRC in IBD and its mortality in patients with and without IBD was tested by logistical regression analyses. RESULTS: Of the 11,446 subjects with IBD, 371 had colon cancer. CRC was diagnosed in 52,243 subjects without IBD. CRC patients with IBD were 7 yr younger than those without IBD, but in patients with Crohn's disease, more cancers were located in the proximal colon (chi 2 = 18.10, df = 5, p = 0.003). The occurrence of CRC in IBD was influenced by the following risk factors: age [odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.35-1.57], sclerosing cholangitis (OR) = 3.41, CI = 2.03-5.73), and history of a disease associated with consumption of nonsteroidal anti-inflammatory drugs (NSAID) (OR = 0.84, CI = 0.65-1.09). Sex, race, and type of IBD did not exert a significant influence on the development of cancer. Cancer-related mortality was influenced by the following risk factors: age (OR = 1.16, CI = 1.14-1.18), male gender (OR = 1.23, CI = 1.06-1.44), white race (OR) = 0.97, CI = 0.96-0.99), and history of NSAID consumption (OR = 0.68, CI = 0.65-0.72). Presence of IBD was not associated with a significant influence on CRC mortality (OR = 1.00, CI = 0.70-1.43). CONCLUSIONS: CRC affects IBD patients at a younger age and is characterized by a more proximal localization when compared with CRC of non-IBD patients. NSAID exert a protective influence against CRC in patients with IBD similarly as in patients without IBD. Sclerosing cholangitis is associated with a strong risk of developing colon cancer in patients with IBD.

Age Distribution↗

PubMed1996

Cost-benefit analysis of testing for Helicobacter pylori in dyspeptic subjects.

OBJECTIVES: It has remained controversial how to manage patients who present with symptoms of dyspepsia. Should all dyspeptic patients undergo a radiological or endoscopic procedure to diagnose peptic ulcer, or would a serological test for Helicobacter pylori provide sufficient evidence to start all H. pylori-positive patients on empirical antibiotic therapy? METHODS: The outcome of serological testing for H. pylori in dyspepsia is analyzed using a decision tree. Successful eradication is associated with the potential benefits of healing dyspepsia and preventing peptic ulcer or gastric cancer. In a sensitivity analysis, all of the transition rates and benefits are varied over a wide range to test the robustness of the calculated decision outcomes. RESULTS: The cost-benefit relationship of serological screening for H. pylori in dyspeptic patients is influenced primarily by the response rate of nonulcer dyspepsia to H. pylori eradication and secondly by the monetary benefit of ulcer prevention and the prevalence rate of peptic ulcer in H. pylori-positive patients. A response to H. pylori eradication in 5-10% of all patients with nonulcer dyspepsia would make screening and treatment for H. pylori a beneficial option, irrespective of any other potential benefits. If ulcer prevention were associated with long term benefit of $4000 or more and if the ulcer prevalence rate exceeded 10% of all dyspeptic patients, serological screening for H. pylori would also pay off. CONCLUSIONS: As long as no unequivocal evidence exists that nonulcer dyspepsia responds to eradication of H. pylori, treating all dyspeptic patients who test positive for H. pylori cannot be recommended. At the present time, antibiotic therapy should be reserved to patients with proven ulcer or to patients with nonulcer dyspepsia for whom other measures have failed.

Anti-Bacterial Agents↗

PubMed1995

Prevention of colorectal cancer by flexible endoscopy and polypectomy. A case-control study of 32,702 veterans.

OBJECTIVE: To determine whether patients with colorectal cancer are less likely than unaffected controls to have had one or more endoscopic procedures (flexible sigmoidoscopy, colonoscopy, or polypectomy) before being diagnosed with cancer. DESIGN: Case-control study. SETTING: Hospitals of the Department of Veterans Affairs. PATIENTS: 8722 and 7629 case-patients with colon and rectal cancer, respectively, and age-, sex-, race-matched controls who were discharged at the same time as the corresponding case-patients. MEASUREMENTS: Number and type of endoscopic procedures of the large bowel done from 1981 until the development of colorectal cancer in each case-patient. The influence of endoscopic procedures on the development of colorectal cancer was tested by conditional multiple logistic regression analysis. RESULTS: Compared with controls, patients with colorectal cancer were less likely to have had an endoscopic procedure of the large bowel before being diagnosed with cancer (odds ratio for colon cancer, 0.51 [95% CI, 0.44 to 0.58]; odds ratio for rectal cancer, 0.55 [CI, 0.47 to 0.64]). In patients who had flexible sigmoidoscopy, colonoscopy, and polypectomy, the odds ratios were even smaller. When analyzed by separate 1-year intervals, patients with cancer had significantly fewer procedures during periods of up to 6 years before their onset of their cancer. Similarly, fewer inpatient and outpatient procedures were done in patients than in controls. CONCLUSIONS: Endoscopic procedures of the large bowel reduce the risk for developing colon and rectal cancer by 50%, their protective influence lasting 6 years.

Aged↗

PubMed1995

Distribution of extracellular and cytoplasmic domains of the alpha 3 and alpha 6 integrin subunits in solid tumors.

Integrins play an important role in malignant transformation and the invasion of tumors. They mediate cell-cell and cell-matrix interactions and participate in transduction of signals across the plasma membrane, processes dependent on the extracellular and cytoplasmic domains of integrins. We studied a selection of solid tumors by immunohistochemistry using monoclonal antibodies (MAbs) against the extracellular domain and the cytoplasmic variants (A and B) of the alpha 3 and alpha 6 integrin subunits. The tissue-specific expression of ecto- and cyto-domains of alpha 3 and alpha 6 is maintained in a subset of breast, colon, kidney and parotid tumors. In a few breast tumors, there was a switch in variant expression in that alpha 6B was detected instead of alpha 6A in normal breast tissue. In many colon and parotid tumors, one of the variants of alpha 6 was missing, while both were detectable in the corresponding normal tissues. In contrast, coexpression of the alpha 6 variants was found in some kidney tumors, whereas only one of the variants was detected in the normal tissue. In a minority of colon and kidney tumors, the cyto-domains of alpha 3 and alpha 6 were undetectable and total absence of alpha 3 and alpha 6 was noted in a subset of breast, colon, kidney and parotid tumors. These observations show that expression of the integrin variants in tumors varies considerably and support the concept that changes in expression may contribute to malignant behavior.

Antibodies, Monoclonal↗

PubMed1995

Protection by endoscopy against death from colorectal cancer. A case-control study among veterans.

BACKGROUND: Although several clinical and epidemiologic studies suggest that timely diagnostic procedures of the large bowel may reduce mortality from colorectal cancer, the evidence for this relationship is primarily circumstantial. METHODS: A case-control study was conducted among hospitalized US military veterans to investigate whether diagnostic procedures of the large bowel were performed in the period preceding the diagnosis of colorectal cancer less frequently in patients dying of colorectal cancer than in control patients. Data files of a total of 4411 veterans dying of colorectal cancer between 1988 and 1992 were extracted from the records of the US Department of Veterans Affairs, Washington, DC. Data of four living control patients and four dead control patients without colorectal cancer were matched by age, sex, and race to each case patient. The case and the two control populations were compared by conditional logistic regression, calculating odds ratios, and their 95% confidence interval. RESULTS: Diagnostic procedures of the large bowel reduced mortality from colorectal cancer, the odds ratio being 0.41 (range, 0.33 to 0.50) for the comparison with living control patients. The protective effects of proctosigmoidoscopy, colonoscopy, and polypectomy lasted for 5 years. The procedures were protective against death from cancer of the colon, as well as cancer of the rectum. The most protective influence was associated with removal of tissue through biopsy, fulguration, and polypectomy. Similar influences were found comparing case patients with dead control patients. CONCLUSION: Removal of tissue represents the most effective means to reduce mortality from cancers of the large bowel. It retains its efficacy over a time period of 5 years.

Aged↗

PubMed1995

A novel beta 1 integrin isoform produced by alternative splicing: unique expression in cardiac and skeletal muscle.

The mRNA's of several integrin subunits are alternatively spliced in the region encoding cytoplasmic domains, that may potentially provide alternative integrin-cytoskeleton interactions and transmembrane signaling pathways. We identified a novel cytoplasmic tail variant of the human beta 1 subunit by reverse transcriptase polymerase chain reaction. This fourth beta 1 variant, named beta 1D, is specific for skeletal and cardiac muscle. The determined genomic organization of the 3'-region of the human beta 1 gene reveals that beta 1D is produced by alternative splicing of mRNA. In addition, we show that the expression of beta 1D is developmentally regulated during murine myoblast differentiation, suggesting a role for beta 1D in myogenesis.

Alternative Splicing↗

PubMed1995

Mouse egg integrin alpha 6 beta 1 functions as a sperm receptor.

Binding between sperm and egg plasma membranes is an essential step in fertilization. Whereas fertilin, a mammalian sperm surface protein, is involved in this crucial interaction, sperm receptors on the egg plasma membrane have not been identified. Because fertilin contains a predicted integrin ligand domain, we investigated the expression and function of integrin subunits in unfertilized mouse eggs. Polymerase chain reactions detected mRNAs for alpha 5, alpha 6, alpha v, beta 1, beta 3, and beta 5. Immunofluorescence revealed alpha 6 beta 1 and alpha v beta 3 on the plasma membrane. GoH3, a function-blocking anti-alpha 6 monoclonal antibody, abolished sperm binding, but a nonfunction-blocking anti-alpha 6 monoclonal antibody, a function-blocking anti-alpha v beta 3 polyclonal antibody, and an RGD peptide had no effect. Somatic cells bound sperm avidly, but only if they expressed alpha 6 beta 1. A peptide analog of the fertilin integrin ligand domain inhibited sperm binding to eggs and alpha 6 beta 1+ cells and diminished GoH3 staining of eggs. Our results indicate a novel role for the integrin alpha 6 beta 1 as a cell-cell adhesion receptor that mediates sperm-egg binding.

ADAM Proteins↗

PubMed1995

Costs of duodenal ulcer therapy with antibiotics.

BACKGROUND: Intermittent or maintenance therapy with histamine2 antagonists, highly selective vagotomy, or antibiotic therapy to eradicate Helicobacter pylori all represent distinct, viable options to manage duodenal ulcer disease. Comparing the costs associated with these four approaches could help in deciding among them. METHODS: The decision model of a Markov chain was used to compare the costs of the four approaches and their influence on the natural course of duodenal ulcers. Direct costs were calculated from the average wholesale prices of drugs and from charges for medical services submitted to and allowed by the Health Care Financing Administration. Average annual income was used to estimate indirect costs. RESULTS: The model predicted that after antibiotic therapy, 99.7% of patient time is spent free of duodenal ulcer. The corresponding percentages were 96.6% for maintenance therapy, 94.4% for vagotomy, 89.4% for intermittent therapy, and 82.8% without therapy. For an individual patient after 15 years, the expected total costs of a treatment approach involving antibiotics are $995, compared with $10,350 for intermittent therapy with histamine2 antagonists, $11,186 for maintenance therapy with histamine2 antagonists, and $17,661 after vagotomy. Incorporating upper gastrointestinal tract endoscopy to verify eradication of H pylori raises the costs of the antibiotic therapy option to $2426. Increasing the annual infection rate of H pylori from baseline 1% to 10% raises the expected costs after 15 years to $3431. Decreasing the H pylori eradication rate from baseline 80% to 50% raises the costs to $2679. CONCLUSIONS: Compared with other options, antibiotics to eradicate H pylori are the cheapest therapy for duodenal ulcer and provide the least time spent with an active ulcer. From an economic perspective, antibiotics represent the treatment of choice.

Anti-Bacterial Agents↗

PubMed1995

Expression patterns of laminin receptor splice variants alpha 6A beta 1 and alpha 6B beta 1 suggest different roles in mouse development.

The alpha 6 beta 1 integrin is a receptor for laminins and is present from early stages of mouse embryogenesis. In the present study we determined the temporal and spatial expression of the two cytoplasmic splice variants of the alpha 6 integrin subunit, alpha 6A and alpha 6B, in the early- and mid-gestation mouse postimplantation embryo using RT-PCR, in situ hybridization, and immunofluorescence. Our results show that alpha 6B is present in the embryo at all stages studied and is expressed before alpha 6A. alpha 6A expression begins in 8.5 day p.c. embryos and is initially exclusively localized to the developing heart. In 8.5 (and 9.5) day p.c. embryos alpha 6A mRNA and protein are present in a gradient in the myocardium of the heart tube from strongest expression in the sinus venosus and in the common atrial chamber to a weakening expression along the ventricle and bulbus cordis. In 10.5 day p.c. embryos this gradient is less evident and in 12.5 day p.c. embryos alpha 6A mRNA and protein are present in comparable amounts between atria and ventricles. Neither alpha 6A nor alpha 6B is present in endocardial cushion tissue. By day 12.5 p.c. alpha 6A expression is also present in the developing epidermis, dental primordia, lens, gonads, and in a few epithelia such as those of the digestive tract. alpha 6B expression is always much more widespread than alpha 6A expression. For example, only alpha 6B is present in the myotome of the somites of 9.5 day p.c. embryos, in the developing central and peripheral nervous systems, and in the nephrogenic system at all stages studied, except after the differentiation of the gonads when alpha 6A is also present. Furthermore, alpha 6B is the only splice variant present on endothelial cells. We also examined the distribution of the beta 4 integrin subunit to determine whether the alpha 6 beta 4 integrin was present during these stages of development. Beta 4 protein was absent in early postimplantation stages but was present in the epidermis and digestive tract of 12.5 day p.c. embryos. These results show a differential distribution of alpha 6A and alpha 6B during mouse development and thus strongly suggest a different function of these splice variants during embryogenesis. Our results point to a possible role for the alpha 6A beta 1 integrin in the development of the myocardium of the developing heart, but not in the migration of endocardial cushion cells, while alpha 6B beta 1 could be important in the developing nephrogenic and nervous systems.

Alternative Splicing↗