Biomedical subjects

A Sonnenberg

Publications and source records attributed to A Sonnenberg.

At least 145 records · Page 8Linked to original sources

PubMed1997

The localization of bullous pemphigoid antigen 180 (BP180) in hemidesmosomes is mediated by its cytoplasmic domain and seems to be regulated by the beta4 integrin subunit.

Bullous pemphigoid antigen 180 (BP180) is a component of hemidesmosomes, i.e., cell-substrate adhesion complexes. To determine the function of specific sequences of BP180 to its incorporation in hemidesmosomes, we have transfected 804G cells with cDNA-constructs encoding wild-type and deletion mutant forms of human BP180. The results show that the cytoplasmic domain of BP180 contains sufficient information for the recruitment of the protein into hemidesmosomes because removal of the extracellular and transmembrane domains does not abolish targeting. Expression of chimeric proteins, which consist of the membrane targeting sequence of K-Ras fused to the cytoplasmic domain of BP180 with increasing internal deletions or lacking the NH2 terminus, indicates that the localization of BP180 in hemidesmosomes is mediated by a segment that spans 265 amino acids. This segment comprises two important regions located within the central part and at the NH2 terminus of the cytoplasmic domain of BP180. To investigate the effect of the alpha6beta4 integrin on the subcellular distribution of BP180, we have transfected COS-7 cells, which lack alpha6beta4 and BP180, with cDNAs for BP180 as well as for human alpha6A and beta4. We provide evidence that a mutant form of BP180 lacking the collagenous extracellular domain as well as a chimeric protein, which contains the entire cytoplasmic domain of BP180, are colocalized with alpha6beta4. In contrast, when cells were transfected with cDNAs for alpha6A and mutant forms of beta4, either lacking the cytoplasmic COOH-terminal half or carrying phenylalanine substitutions in the tyrosine activation motif of the cytoplasmic domain, the recombinant BP180 molecules were mostly not colocalized with alpha6beta4, but remained diffusely distributed at the cell surface. Moreover, in cells transfected with cDNAs for alpha6A and a beta4/beta1 chimera, in which the cytoplasmic domain of beta4 was replaced by that of the beta1 integrin subunit, BP180 was not colocalized with the alpha6beta4/beta1 chimera in focal adhesions, but remained again diffusely distributed. These results indicate that sequences within the cytoplasmic domain of beta4 determine the subcellular distribution of BP180.

Animals↗

PubMed1997

Spatial and temporal expression of the beta1D integrin during mouse development.

The beta1D protein is a recently characterized isoform of the integrin beta1 subunit that is present in cardiac and skeletal muscles. In this study, we have examined the expression of beta1D in different types of skeletal muscle and in cardiac muscle and studied its distribution during mouse development, using new monoclonal antibodies specific for beta1D. Immunoprecipitation studies revealed that, while beta1A is strongly expressed in proliferating C2C12 myoblasts, beta1D is only expressed after their differentiation to myotubes. In these myotubes, beta1D is associated with different alpha subunits, namely alpha3A, alpha5, alpha7A, or alpha7B. Initially, during embryogenesis, the alpha1A subunit is the only beta1 variant expressed in skeletal and cardiac muscle. The beta1D subunit is first detected in skeletal muscle at E17.5, whereas in cardiac muscle its expression begins around the time of birth. Later the expression of beta1A in skeletal and cardiac muscle becomes restricted to capillary cells, whereas beta1D eventually becomes the only variant expressed in adult cardiac and skeletal muscle cells. The switch from the beta1A to the beta1D subunit in cardiac muscle cells coincides with the expression of alpha7. In adults there is a distinct concentration of beta1D at the myotendinous junctions of muscle fibers and at costameres in both cardiac and skeletal muscle. In addition, beta1D is present at intercalated discs in cardiac muscle and at neuromuscular junctions in skeletal muscle cells. The amount of beta1D in different types of skeletal muscle (fast, slow, and mixed-type) was similar, but cardiac muscle expressed almost five times as much of this protein. We suggest that beta1D plays a role in the maintenance of the cytoarchitecture of mature muscle and in the functional integrity of the muscle cells.

Animals↗

PubMed1997

Implications of intragenic marker homozygosity and haplotype sharing in a rare autosomal recessive disorder: the example of the collagen type XVII (COL17A1) locus in generalised atrophic benign epidermolysis bullosa.

Generalised atrophic benign epidermolysis bullosa (GABEB) is a form of junctional epidermolysis bullosa with a recessive mode of inheritance. The gene considered likely to be involved in this disease is COL17A1, since in the majority of GABEB patients the product of that gene, the 180-kD bullous pemphigoid antigen (BP180), is undetectable in skin. We have identified an intragenic COL17A1 microsatellite marker for which 83% of randomly selected control individuals are heterozygous. We observed homozygosity for different alleles of this marker in five out of six collagen type XVII-negative GABEB patients of different European descent. Five of the six COL17A1 alleles of three patients originating from the eastern part of the Netherlands were identical, as were the haplotypes including flanking markers. The 2342delG mutation was identified in all these five alleles. This confirms the expectation that due to genetic drift and hidden inbreeding for an autosomal recessive disorder with low gene frequency, such as collagen type XVII-negative GABEB, most disease alleles from a restricted geographical area will be "identical by descent". Our results demonstrate that involvement of a candidate gene can be confirmed by looking for identity by descent of highly informative intragenic markers.

Adult↗

PubMed1997

Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United States military veterans.

BACKGROUND & AIMS: It has been speculated that gastroesophageal reflux disease (GERD) represents a risk factor for the occurrence of extraesophageal complications. The aim of this study was to compare the comorbid occurrence of sinus, laryngeal, and pulmonary diseases in case subjects with and control subjects without reflux esophagitis. METHODS: The case population consisted of all patients with erosive esophagitis (International Classification of Diseases code 530.1) or esophageal stricture (ICD code 530.3) who were discharged from hospitals of the Department of Veteran Affairs between 1981 and 1994. In multivariate logistic regressions, the occurrence of sinus, pharyngeal, laryngeal, or pulmonary disease was compared between cases with and an equal number of controls without esophagitis or stricture. RESULTS: A total of 101,366 case subjects was analyzed. Erosive esophagitis and esophageal stricture were associated with sinusitis (odds ratio, 1.60; 95% confidence interval, 1.51-1.70), pharyngitis (1.48; 1.15-1.89), aphonia (1.81; 1.18-2.80), laryngitis (2.01; 1.53-2.63), laryngeal stenosis (2.02; 1.12-3.65), chronic bronchitis (1.28; 1.22-1.34), asthma (1.51; 1.43-1.59), chronic obstructive pulmonary disease (1.22; 1.16-1.27), pulmonary fibrosis (1.36; 1.25-1.48), bronchiectasis (1.26; 1.09-1.47), pulmonary collapse (1.31; 1.23-1.40), and pneumonia (1.15; 1.12-1.18). CONCLUSIONS: Patients with reflux esophagitis are at an increased risk of harboring a large variety of sinus, pharyngeal, laryngeal, and pulmonary diseases.

Aged↗

PubMed1997

Cost-analysis of prophylactic antibiotics in spontaneous bacterial peritonitis.

BACKGROUND & AIMS: Antibiotic prophylaxis has been shown to decrease the incidence of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites. The aim of this study was to test whether antibiotic prophylaxis for SBP is cost-effective and to compare the costs associated with different patient groups and treatment strategies. METHODS: A cost-effectiveness analysis was performed using a Markov chain model. The costs incurred during 1-year treatment with prophylactic antibiotics vs. no prophylaxis in patients with cirrhosis and ascites were calculated. The incidence rates of primary and recurrent SBP and the mortality rate of SBP were obtained from the literature. Total direct costs of SBP treatment were determined from the wholesale price of drugs and from disbursements by the Health Care Financing Administration. RESULTS: Norfloxacin prophylaxis resulted in savings between $2216 and $8545 per patient per year, depending on the patient group studied. Trimethoprim-sulfamethoxazole prophylaxis resulted in savings between $2934 and $9251 per patient per year. The groups that benefited most from prophylaxis were patients with an ascitic fluid total protein concentration of < or = 1 g/dL and those with a previous history of SBP. CONCLUSIONS: The use of prophylactic antibiotics to decrease the incidence of SBP is a cost-saving strategy in patients with cirrhosis and ascites.

Antibiotic Prophylaxis↗

PubMed1997

Integrin alpha 6 beta 4 forms a complex with the cytoskeletal protein HD1 and induces its redistribution in transfected COS-7 cells.

The integrin alpha 6 beta 4 is a major component of hemidesmosomes, in which it is linked to intermediate filaments. Its presence in these structures is dependent on the beta 4 cytoplasmic domain but it is not known whether beta 4 interacts directly with keratin filaments or by interaction with other proteins. In this study, we have investigated the interaction of GST-cyto beta 4A fusion proteins with cellular proteins and demonstrate that a fragment of beta 4A, consisting of the two pairs of fibronectin type III repeats, separated by the connecting segment, forms a specific complex containing a 500-kDa protein that comigrates with HD1, a hemidesmosomal plaque protein. A similar protein was also bound by a glutathione S-transferase fusion protein containing the cytoplasmic domain of a variant beta 4 subunit (beta 4B), in which a stretch of 53 amino acids is inserted in the connecting segment. Subsequent immunoblot analysis revealed that the 500-kDa protein is in fact HD1. In COS-7 cells, which do not express alpha 6 beta 4 or the hemidesmosomal components BP230 and BP180, HD1 is associated with the cytoskeleton, but after transfecting the cells with cDNAs for human alpha 6 and beta 4, it was, instead, colocalized with alpha 6 beta 4 at the basal side of the cells. The organization of the vimentin, keratin, actin, and tubulin cytoskeletal networks was not affected by the expression of alpha 6 beta 4 in COS-7 cells. The localization of HD1 at the basal side of the cells depends on the same region of beta 4 that forms a complex containing HD1 in vitro, since the expression of alpha 6 with a mutant beta 4 subunit that lacks the four fibronectin type III repeats and the connecting segment did not alter the distribution of HD1. The results indicate that for association of alpha 6 beta 4 with HD1, the cytoplasmic domain of beta 4 is essential. We suggest that this association may be crucial for hemidesmosome assembly.

Animals↗

PubMed1997

Economic analysis of dyspepsia.

A variety of organic and non-organic diseases can present with symptoms of dyspepsia or upper abdominal pain, and a large diagnostic and therapeutic armamentarium is available to manage symptoms of dyspepsia. How extensively should a diagnostic search be conducted; and where does the best path run through the maze of potential combinations of tests and therapies? Physicians have hoped that economic and medical decision analyses would help them to find the most cost-effective and most efficacious means to deal with dyspepsia. Because of the large variety of potential diagnoses, diagnostic procedures and therapeutic means, however, it is very doubtful that a single most effective or least expensive strategy can ever be developed to apply to every patient with dyspepsia. Following the lines of common medical sense is probably more cost-effective than observing a rigid regimen derived from an economical analysis.

Costs and Cost Analysis↗

PubMed1997

Mitochondrial Haplotype Influences Mycelial Growth of Agaricus bisporus Heterokaryons.

We evaluated the influence of mitochondrial haplotype on growth of the common button mushroom Agaricus bisporus. Ten pairs of heterokaryon strains, each pair having the same nuclear genome but different mitochondrial genomes, were produced by controlled crosses among a group of homokaryons of both wild and commercial origins. Seven genetically distinct mitochondrial DNA (mtDNA) haplotypes were evaluated in different nuclear backgrounds. The growth of heterokaryon pairs differing only in their mtDNA haplotypes was compared by measuring mycelial radial growth rate on solid complete yeast medium (CYM) and compost extract medium and by measuring mycelial dry weight accumulation in liquid CYM. All A. bisporus strains were incubated at temperatures similar to those utilized in commercial production facilities (18, 22, and 26(deg)C). Statistically significant differences were detected in 8 of the 10 heterokaryon pairs evaluated for one or two of the three growth parameters measured. Some heterokaryon pairs showed differences in a single growth parameter at all three temperatures of incubation, suggesting a temperature-independent difference. Others showed differences at only a single temperature, suggesting a temperature-dependent difference. The influence of some mtDNA haplotypes on growth was dependent on the nuclear genetic background. Our results show that mtDNA haplotype can influence growth of A. bisporus heterokaryons in some nuclear backgrounds. These observations demonstrate the importance of including a number of mitochondrial genotypes and evaluating different nuclear-mitochondrial combinations of A. bisporus in strain improvement programs.

Journal Article↗

PubMed1997

Relation between gastric cancer and previous peptic ulcer disease.

BACKGROUND: It is presently not well understood to what extent peptic ulcer and gastric cancer represent related diseases. AIMS: The objective of this study was to assess past occurrence of gastric and duodenal ulcers in patients with cancer of the gastric cardia or other parts of the stomach. METHODS: The association between peptic ulcer and gastric cancer was studied among patients followed up at hospitals of the US Department of Veterans Affairs. Two populations of 1069 subjects with cancer of the cardia and 3078 subjects with cancer of other parts of the stomach were compared with a control population of 89082 subjects without gastric cancer. In multivariate logistic regressions, presence or absence of cancer served as the outcome variable, while age, sex, race, previous histories of gastric ulcer, duodenal ulcer, peptic ulcer site unspecified, gastric resection, or vagotomy served as modifier variables. RESULTS: Old age, non-white ethnicity, and male sex proved strong and independent risk factors for non-cardiac gastric cancer. A previous history of gastric, but not duodenal ulcer was associated with a significantly raised odd ratio of 1.53 (95% confidence interval: 1.24 to 1.87). Cancer of the cardia affected predominantly whites, and was relatively more common in men than non-cardiac gastric cancer. Past gastric ulcers exerted no significant influence (1.02, 0.67 to 1.56), while duodenal ulcers and peptic ulcer site unspecified were protective (duodenal ulcer: 0.68, 0.47 to 0.95; peptic ulcer disease: 0.66, 0.47 to 1.00). Partial gastrectomy was a risk factor for non-cardiac gastric cancer (1.86, 1.32 to 2.63), but not for cancer of the cardia (1.09, 0.54 to 2.20). CONCLUSION: These epidemiological patterns might stem from underlying differences in the influences of gastritis and acid secretion on the development of the two cancer types.

Aged↗

PubMed1997

Associations between different forms of gastro-oesophageal reflux disease.

AIMS: To study the epidemiology and natural history of gastro-oesophageal reflux disease (GORD). METHODS: Retrospective cohort study involving all 172 hospitals of the Department of Veterans Affairs. A total of 194,527 patients with GORD were followed between 1981 and 1994. Distribution of oesophagitis, oesophageal ulcer, oesophageal stricture, strictured hiatus hernia, hiatus hernia, and pyrosis by age, sex, and ethnicity were determined. The comorbid occurrence of various forms of GORD in identical patients was analysed by an age and race standardised morbidity ratio. The population of all hospitalised veterans was used for comparison. RESULTS: Severe forms of GORD associated with oesophageal erosions, ulcers, or strictures, affected elderly, white, male patients more often than their corresponding opposite demographic group. All forms of GORD clustered in the same patient population; on average, any form of GORD was 10 times more likely to occur in a patient with another form of GORD than without. The highest morbidity ratio (22) was found in oesophageal ulcer and stricture. About one third of all patients with oesophageal erosions, ulcers, or strictures also had hiatus hernia; 46% of patients with hiatus hernia were diagnosed as having other forms of GORD. While one third of all oesophageal strictures appeared in patients without other forms of GORD diagnosed at any time, oesophageal ulcers were always associated with some other form of GORD. No clear cut progression in different forms of GORD was found. CONCLUSIONS: Older age, male sex, and white ethnicity are risk factors in the development of severe forms of GORD. The most severe grade of GORD is reached at the onset of the disease.

Aged↗

PubMed1997

A minimal region on the integrin beta4 subunit that is critical to its localization in hemidesmosomes regulates the distribution of HD1/plectin in COS-7 cells.

The integrin alpha6 beta4 is a major component of hemidesmosomes, in which it mediates firm adhesion to laminin 5. Previous studies have shown that the incorporation of alpha6 beta4 into hemidesmosomes requires a 303 amino acid stretch of the cytoplasmic domain of beta4, comprising part of the first fibronectin type III (FNIII) repeat, the second FNIII repeat and the segment that connects the second to the third FNIII repeat (connecting segment). Now, we have further defined sequences within beta4 that are critical for its localization in hemidesmosomes and we demonstrate that these sequences also induce the redistribution of HD1/plectin into junctional complexes containing the integrin alpha6 beta4 in COS-7 cells, transfected with cDNAs encoding alpha6A and beta4. Truncation of the cytoplasmic domain of beta4 after amino acids 1,382 or 1,355 in the connecting segment, by which a potential tyrosine activation motif (TAM) is removed, does not prevent the localization of alpha6 beta4 in hemidesmosomes in the rat bladder carcinoma cell line 804G and neither did it eliminate the ability of alpha6 beta4 to change the subcellular distribution of HD1/plectin in COS-7 cells. In contrast, beta4 subunits in which the entire connecting segment had been deleted or which were truncated after amino acid 1,328, which removes almost the complete segment, had lost both of these functions. Furthermore, when beta4 subunits with either a deletion of the second FNIII repeat or a small deletion in this repeat were co-expressed with alpha6, the integrins were not localized in hemidesmosomes and did not induce the redistribution of HD1/plectin in COS-7 cells. Finally, the fourth FNIII repeat of beta4 could not replace the second in either of these activities. These findings establish that a region in beta4, which encompasses the second FNIII repeat and a stretch of 27 amino acids (1,329-1,355) of the connecting segment, is critical for the localization of alpha6beta4 in hemidesmosomes and that it regulates the distribution of HD1/plectin.

Amino Acid Sequence↗

PubMed1997

The subcellular distribution of the high molecular mass protein, HD1, is determined by the cytoplasmic domain of the integrin beta 4 subunit.

The high molecular mass protein, HD1, is a structural protein present in hemidesmosomes as well as in distinct adhesion structures termed type II hemidesmosomes. We have studied the distribution and expression of HD1 in the GD25 cells, derived from murine embryonal stem cells deficient for the beta 1 integrin subunit. We report here that these cells possess HD1 but not BP230 or BP180; two other hemidesmosomal constituents, and express only traces of the alpha 6 beta 4 integrin. By immunofluorescence and interference reflection microscopy HD1 was found together with vinculin at the end of actin filaments in focal contacts. In OVCAR-4 cells, derived from a human ovarian carcinoma which, like GD25 cells, only weakly express alpha 6 beta 4, HD1 was also localized in focal contacts. Upon transfection of both GD25 and OVCAR-4 cells with cDNA for the human beta 4 subunit the subcellular distribution of HD1 changed significantly. HD1 is then no longer present in focal contacts but in other structures at cell-substrate contacts, colocalized with alpha 6 beta 4. These junctional complexes are probably the equivalent of the type II hemidesmosomes. Transfection of GD25 cells with beta 1 cDNA did not affect the distribution of HD1, which indicates that the localization of HD1 in focal contacts was not due to the absence of beta 1. Moreover, in GD25 cells transfected with cDNA encoding a beta 4/beta 1 chimera, in which the cytoplasmic domain of beta 4 was replaced by that of beta 1, the distribution of HD1 was unaffected. Our findings indicate that the cytoplasmic domain of beta 4 determines the subcellular distribution of HD1 and emphasize the important role of alpha 6 beta 4 in the assembly of hemidesmosomes and other junctional adhesive complexes containing HD1.

Animals↗

PubMed1997

Economic aspects of endoscopic screening for intestinal precancerous conditions.

The relationship of costs to effectiveness in endoscopic screening depends on the incidence rate of cancers arising from precancerous lesions, the sensitivity and specificity rates of endoscopic screening, and the effectiveness of timely diagnosis and surgery in preventing death. Because all these parameters, which enter a medical decision analysis, have a relatively large margin of error, it is not possible to resolve the issue whether a screening should be performed based on economic analyses alone. A crude "back of the envelope" comparison of different screening programs suggests that colonoscopy in ulcerative colitis would result in the highest yield and gastroscopy of the gastric stump in the lowest yield.

Barrett Esophagus↗

PubMed1997

Association of esophagitis and esophageal strictures with diseases treated with nonsteroidal anti-inflammatory drugs.

BACKGROUND: It has been speculated that intake of nonsteroidal anti-inflammatory drugs (NSAIDs) represents a risk factor for the occurrence of esophagitis and esophageal strictures. METHODS: A case-control study was conducted to compare the occurrence of comorbid diseases treated with NSAIDs in case and control subjects with and without esophageal disease, respectively. The case population was comprised of all patients with esophagitis (International Classification of Diseases code 530.1) or esophageal stricture (code 530.3) who were discharged from hospitals of the Department of Veteran Affairs between 1981 and 1994. In separate multivariate logistic regressions, the occurrence of esophagitis or esophageal stricture served as the outcome variable, and age, gender, ethnicity, and comorbid occurrence of an NSAID-related diagnosis served as modifier variables. RESULTS: A total of 101,366 individual case subjects were included, of whom 92,860 presented with esophagitis and 14,201 with stricture. The occurrence of erosive esophagitis was associated with osteoarthritis (odds ratio = 1.42, 95% confidence interval = 1.36-1.48), osteoporosis (1.38, 1.25-1.52), back pain (1.49, 1.42-1.56), femur bone fracture (1.46, 0.92-2.32), fibrositis (1.57, 1.41-1.75), tension headache (1.34, 1.27-1.40), ankylosing spondylitis (1.33, 1.24-1.42), rheumatoid arthritis (1.13, 1.05-1.21), sicca syndrome (1.15, 1.05-1.26), and systemic sclerosis (6.16, 4.65-8.14). NSAID-related diagnoses represented similar risk factors for both esophagitis and esophageal stricture. CONCLUSIONS: A large variety of diseases treated by NSAIDs are associated with a significantly increased risk of esophageal erosion or stricture; the risk appears similar for both of these. In some comorbid conditions, the underlying disease process may contribute to the occurrence of esophageal pathology.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1997

Colorectal cancer after gastric surgery: a meta-analysis.

BACKGROUND: Until now, the question of whether previous gastric surgery results in an increased risk of colorectal cancer has remained controversial. A meta-analysis was performed to resolve this issue. METHODS: The numbers of colorectal tumors in the two populations with and without gastric surgery were retrieved from all relevant articles found through a MEDLINE search. If available, the most detailed breakdown of the data by patient gender, type of peptic ulcer, type of surgery, time since gastric surgery, and by tumor location was chosen. The Mantel-Haenszel procedure was used to calculate a weighted odds ratio from the individual studies. The method of DerSimonian and Laird was used to calculate a weighted average of the difference between tumor rates in patients with and without gastric surgery. RESULTS: The summary odds ratio was 1.09 with a 95% confidence interval of 0.96-1.24. The length of time after surgery, gender, tumor location, initial ulcer type, and different types of surgery were not associated with any significant influence. The summary rate difference was not significantly different from zero. The test for heterogeneity yielded a chi 2 = 26.87, df = 13, p = 0.013. After ignoring one obvious outlier study, the chi 2 test dropped to a nonsignificant level. A L'Abbé plot failed to show any prevailing influence of rate size on the overall heterogeneity among the various studies. CONCLUSIONS: Surgery for peptic ulcer does not result in an increased risk for colorectal tumors. This lack of influence was shown consistently by all tests of the present meta-analysis.

Cohort Studies↗

PubMed1997

The A and B variants of the alpha 3 integrin subunit: tissue distribution and functional characterization.

The alpha subunits of the laminin-binding integrins alpha 3 beta 1, alpha 6 beta 1, and alpha 7 beta 1 have homologous sequences and are similar in structure. Two cytoplasmic variants, A and B, have been identified for each of these alpha subunits, although the alpha 3B splice variant has been detected only at the mRNA level. We prepared a panel of mouse monoclonal antibodies specific for the A and B variants of the alpha 3 subunit to study their tissue distribution. Four monoclonal antibodies react with alpha 3A, one of which recognizes only the nonphosphorylated form; of the three anti-alpha 3B antibodies, one cross-reacts with alpha 6B. Reverse transcriptase-PCR analysis of various human tissues revealed the presence of alpha 3B mRNA in brain, heart, and skeletal muscle. Moreover, the alpha 3B protein was detected by immunoblotting in brain and heart tissue but not in skeletal muscle. In contrast, alpha 3A mRNA and protein were present in all tissues studied. Thus, the expression of alpha 3B in adult tissues is more restricted than that of alpha 3A. Immunohistochemical studies showed that in brain tissue, both variants are exclusively expressed on small blood-vessel endothelium, whereas in heart tissue their distribution patterns differ markedly. Although alpha 3A is strongly expressed on vascular smooth muscle cells, alpha 3B is detected only on endothelial cells of veins. Expression of the two variant forms of alpha 3 in K562 cells revealed that the ligand-binding specificities of alpha 3A beta 1 and alpha 3B beta 1 are identical: both bind human laminin-2 and -4, laminin-5, and laminins isolated from bovine kidney, but not bovine laminin-2 and -4, mouse laminin-1, or human fibronectin. In addition, adhesion mediated by both integrins is induced to the same extent by phorbol 12-myristate 13-acetate. The alpha 3A, but not the alpha 3B subunit, is phosphorylated; and phosphorylation of alpha 3A increases after phorbol 12-myristate 13-acetate stimulation. Thus, we found no differences between the adhesion functions of the A and B variants of alpha 3.

Amino Acid Sequence↗

PubMed1997

Health impact of peptic ulcer in the United States.

OBJECTIVES: To assess the general outcome and impact of current and previous peptic ulcer disease on health status 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. Various measures of impaired health in ulcer patients were expressed by their age- and sex-standardized prevalence rates. RESULTS: Ten to 15% of all subjects with a recent ulcer reported that they had been in poor health, incapable of major activity, or unable to work for some time during the 12 months preceding the interview. Twenty to 25% of the subjects with recent ulcers complained about restricted activity and had spent 7 or more days per year in bed. About 40% of all ulcer subjects had seen a physician five or more times within 12 months before the interview. These percentages were significantly lower in patients with previous ulcer histories but no active ulcer within 12 months, but they were still significantly higher than in subjects with no ulcer history at all. In the United States, expenditures attributed to recent ulcers amounted to $5.65 billion per year. CONCLUSIONS: In the United States, peptic ulcer disease is associated with major morbidity. Ulcer cure would result in large economic and medical savings.

Adolescent↗

PubMed1996

The role of the cytoplasmic domain of alpha 6 integrin in the assembly and function of alpha 6 beta 1 and alpha 6 beta 4.

We have studied the role of the cytoplasmic domain of alpha 6 in the assembly and function of the alpha 6 beta 4 integrin, and compared it with the role of alpha 6 in the assembly and function of alpha 6 beta 1, by transfection of cDNAs encoding cytoplasmic mutants of alpha 6 into K562 cells with or without full-length beta 4 cDNA. Des-(1022-1050)-alpha 6, which contains a deletion C-terminal to the GFFKR motif, was expressed in association with beta 1, but associated preferentially with beta 4, whereas the wild-type alpha 6 subunit associated efficiently with beta 1 and beta 4. Des-(1016-1050)-alpha 6, which lacked also the GFFKR sequence, was only expressed at the cell surface when beta 4 was available. Transient expression in COS-7 cells showed that des-(1016-1050)-alpha 6 was retained in the endoplasmic reticulum as a monomer, which suggests that truncation of the cytoplasmic domain reduces the affinity of alpha 6 for beta 1, particularly when the GFFKR sequence is absent. Although the GFFKR motif is not essential for association of alpha 6 with beta 4, it increases the stability of the alpha 6 beta 4 integrin. The cytoplasmic domain of alpha 6 is essential for inside-out and outside-in signaling via the alpha 6 beta 1 receptor, but not for adhesion via alpha 6 beta 4. We show that alpha 6 beta 4 is a constitutively active receptor. Thus, unlike adhesion by most other integrins, adhesion by alpha 6 beta 4 does not seem to depend on any active cellular process. Binding of alpha 6 beta 4 to ligand was only slightly affected by truncation of the alpha 6 cytoplasmic domain N-terminal to the GFFKR sequence and became partially dependent on metabolic energy. These data indicate that truncations of the cytoplasmic domain of the alpha 6 subunit affect the assembly and function of alpha 6 beta 1 more strongly than those of alpha 6 beta 4. This difference may be due to the greater affinity of alpha 6 for beta 4 than for beta 1, which makes alpha 6 beta 4 less susceptible to the effect of truncations.

Amino Acid Sequence↗