MICA rather than MICB,TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis

OBJECTIVE: To analyze the genetic contribution of HLA in development of psoriatic arthritis (PsA) and to study whether MICA is primarily associated with PsA or whether its association is secondary to linkage disequilibrium with centromeric genes, such as MICB, TNFA, or HLA-DRB1. METHODS: DNA samples from 81 Spanish patients with PsA and 110 healthy controls were examined by polymerase chain reaction (PCR) sequence-specific primers to type HLA-Cw and HLA-DRB1, PCR sequence-specific oligonucleotides to determine HLA-B, and PCR restriction fragment length polymorphism for tumor necrosis factor-alpha promoter polymorphisms at positions -238 and -308. Analysis of microsatellite polymorphisms in the transmembrane region of MICA and in intron 1 of MICB was also carried out. RESULTS: HLA-Cw*0602 was significantly increased in PsA [60% vs 17%; p(c) < 0.00002, OR 7.33, etiological fraction (EF) 0.52]. MICA-A9 (60% vs 30%; p(c) = 0.0002, OR 3.57, EF 0.43) and the microsatellite MICB-CA-22 allele (23% vs 7%; p(c) = 0.028, OR 3.9, EF 0.17) were also significantly increased in PsA. MICA-A9 was in linkage disequilibrium with MICB-CA-22 (delta = 0.6). The association of MICA-A9 was independent of MICB-CA-22 and Cw*0602, since it was also associated in MICB-CA-22 negative (p(c) = 0.0015, OR 2.96, EF 0.34) and in Cw*0602 negative patients (p(c) = 0.034, OR 2.83, EF 0.34). TNFA and DRB I alleles were not significantly associated with PsA. CONCLUSION: Cw*0602 and MICA-A9 appear to be the strongest genetic susceptibility factors for PsA. However, MICA-A9 was associated independently of Cw6. HLA-B alleles and MICB-CA22 are associated secondarily to linkage with MICA. TNFA and HLA-DRB1 were not associated with PsA susceptibility, and our data suggest that their reported association may only reflect the linkage disequilibrium with MICA-A9 among the different populations studied.     

Changes in disability before and after myocardial infarction in older adults

BACKGROUND: Disability in older adults is thought to occur primarily as a consequence of clinical disease episodes. However, the temporal relationship between clinical disease and disability has received little systematic attention. METHODS: Data from a prospective population-based study of 2812 older adults were analyzed to examine changes in disability before and after acute myocardial infarction. Disability outcomes included up to 9 yearly assessments of disability in activities in daily living, disability in basic physical functions, and disability in tasks requiring basic mobility and strength. RESULTS: A total of 279 myocardial infarctions occurred during 9 years of follow-up. After adjustment for age and sex, the average yearly increase in disability in activities of daily living and basic physical functions was not significantly greater in the 1-year period after myocardial infarction than in the 3-year period before myocardial infarction (P values >.20). Disability in basic mobility and strength showed a significantly greater increase in the year after myocardial infarction (P = .02). The results did not change after adjustment for comorbidity and chest pain or when restricted to incident cases of myocardial infarction or survivors. An additional exploratory analysis suggested that the rate of increase in some forms of disability may start to accelerate at about 1 year before the event, rather than after the event. CONCLUSIONS: The increase in disability after myocardial infarction may form a continuation of increases that occur before the event and challenge commonly held notions about the temporal relationship between clinical disease and disability. Changes in disability before acute disease episodes may be related to subclinical disease.     

Nonsurgical treatment of drooling in a patient with closed head injury and severe dysarthria

The purpose of this investigation was to measure the effectiveness of the antimuscarinic drug atropine sulfate in the treatment of chronic drooling in a patient with a history of severe closed head injury and resultant widespread oral neuromuscular and higher cortical disturbances. Results of the A-B-A-B-A-B withdrawal paradigm, chosen to demonstrate the functional relationship between drug therapy and the degree of drooling, revealed that administration of atropine sulfate reduced by more than 50% of baseline levels the amount of resting secretion, intraoral accumulation, and pharyngeal-laryngeal pooling of saliva, with negligible side effects. These results are discussed and compared to the alternative drug and surgical approaches to the alternative drug and surgical approaches to treatment that have been the primary focus of recent research on drooling.     

Intracellular trafficking during liver regeneration. Alterations in late endocytic and transcytotic pathways

BACKGROUND/AIMS: Liver growth, induced by partial hepatectomy of the organ is a precisely regulated process during which a radical reorganisation of metabolism occurs as the hepatocytes become committed to enter the cell cycle. Recent studies have shown the importance of the endocytic compartment in the control of lipid and protein intracellular trafficking but also in the control of the signal transduction events, which eventually will trigger the initiation of DNA synthesis and the subsequent cell division. METHODS: We isolated endosomes at different times after partial hepatectomy in male rats and compared with endosomes isolated from sham-operated animals. Also, bile was collected and analysed by 2D-gel electrophoresis. RESULTS: The amount of late endosomes isolated from regenerating livers decreased, concomitant with decreased cathepsin D specific enzyme activity. Furthermore, secretion of horseradish peroxidase, pIgA and transferrin increased in the pre-replicative phase of liver regeneration. CONCLUSIONS: At the early stages of liver regeneration, the hepatocellular transport pathway towards degradation (late endosomes and lysosomal pathway) decreases, but the transcytosis and the bile secretion of several major proteins increases.     

The concerted mechanism of photo-induced biprotonic transfer in 7-azaindole dimers: a model for the secondary evolution of the classic C2h dimer and comparison of four mechanisms

A mechanism is proposed for the formation in gas phase, during a short time, of the delicately symmetrical coplanar C(2h) classic 7-azaindole (7AI) doubly hydrogen-bonded dimer. Of the five card-pack or otherwise random geometry structures most likely to be formed in the supersonic jet expansion molecular beam, none would be an obvious precursor to the C(2h) dimer. One unstable dimer with dipole-dipole, van der Waals, and plane-to-plane hydrogen bonding is shown to be capable of unhinging about the hydrogen-bond pair as an axis, from 0 degrees to 90 degrees to 180 degrees, yielding a deep minimum for the C(2h) structure with its delicate geometry and symmetry. This relaxation mechanism is feasible in the 3-micros interval between the nozzle escape and the first laser pulse interception of the molecular beam. In the second part of the paper four published mechanisms are compared for concerted vs. two-step biprotonic phototransfer for the 7AI dimers. The dependence of the latter two models on H-atom instead of proton-transfer as an intermediate step negates the mechanism in a singlet (pi,pi*) electronic state by the valency repulsion, in the 3-electron orbital that would be generated. The concerted mechanism for biprotonic phototransfer is reaffirmed by the analysis of the quantum mechanical conditions set on the biprotonic transfer in the photo-excited molecular 7AI pair.     

Association of Sjögren's syndrome and rosacea: a diagnostic challenge

Both Sjögren's syndrome and rosacea present clinical manifestations that include ocular involvement. We report a case of a 45‐year‐old woman with a history of persistent erythematous malar rash, associated with conjunctival hyperemia, xerophthalmia and blefaritis. The patient filled the current classification criteria proposed for Sjögren's syndrome and those for rosacea. The coexistence of these diseases has not been previously described in the literature. Both diseases have similar symptoms and different treatment approaches. We believe that it is important for clinicians to identify this association in order to provide better care for the patient.     

Primary neoplasms of the liver: The possibility of biochemical diagnosis

Summary 1. In 168 necropsies performed during a period of less than 3 years, 6 cases of primary carcinoma of the liver were found, an incidence of 3.57%. Another case was proved by needle biopsy, but autopsy was not obtained. Six of the 7 carcinomas were diagnosed during the life of the patients concerned.2. Clinical diagnosis was established upon a history of progressive and rapid general deterioration of health, with anorexia and marked emaciation accompanied by painful nodular hepatomegaly and fever, and later by moderate jaundice and serosanguineous ascitic effusion.3. The disproportion between the slightly elevated values of serum bilirubin and the high alkaline phosphatase activity, together with an increase of the transaminase levels, were the most important laboratory data, allowing the diagnosis of expanding space-occupying lesion (though not specifying its precise nature).The practical application of these criteria to diagnosis may be rewarded with an increase in in-vivo diagnosis of neoplasms of the liver.Pathologic examinations were carried out at the Instituto de Anatomia Patológica.     

In vitro preliminary study of osteoblast response to surface roughness of titanium discs and topical application of melatonin

Objectives: To observe human osteoblast behavior cultured in vitro on titanium discs (Ti) in relation to surface roughness and melatonin application. Study Design: Human osteoblasts (MG-63) were cultured on 60 Ti6Al4V discs divided into three groups: Group I: discs treated with dual acid etching; Group II dual acid etching and blasting with calcium phosphate particles; Group III (control) machined discs. Surface roughness and topography of the discs were examined with scanning electron microscope (SEM) and confocal laser scanning electron microscope( CLSM). Osteoblast adhesion, proliferation and cell morphology were determined by means of fluorescence microscopy with Image-Pro Plus software and SEM. Results: Group II presented the roughest discs, while the least rough were Group III. Cell adhesion was greatest in Group II. The addition of melatonin improved cell proliferation. Conclusions: 1. Surface treatments (dual acid etching, calcium phosphate impaction) increase surface roughness in comparison with machined titanium. 2. Greater surface roughness tends to favor cell adhesion after 24-hour cell culture. 3. The addition of melatonin tends to favor osteoblast proliferation. Key words:Osteoblasts, titanium, roughness, melatonin, dental implants, osseointegration.