Tyrosine phosphorylation of the erythropoietin receptor: role for differentiation and mitogenic signal transduction

The erythropoietin (Epo) receptor belongs to the cytokine receptor superfamily. Although the cytokine receptors do not possess a tyrosine kinase consensus sequence in the intracellular domain, rapid stimulation of a tyrosine kinase activity occurs after activation by the ligand. We and others have shown that Epo induces the tyrosine phosphorylation of its cognate receptor as well as phosphorylation of other proteins. In this report, we examined the role of the receptor tyrosine residues in signal transduction. Eight tyrosine residues are located within the intracellular domain of the murine Epo receptor. A single tyrosine residue is present in the region previously shown to be sufficient for proliferative signal transduction. This tyrosine (Tyr 343) was mutated to phenylalanine. Moreover, mutant receptors were also generated with either a tyrosine residue or a phenylalanine residue at position 343 and with a COOH terminal truncation that removed the 7 other tyrosine residues. Expression vectors carrying these mutated receptors were transfected into the interleukin-3-dependent murine cell line Ba/F3. Epo-induced growth was sustained efficiently by all these receptors, although receptors without any tyrosine residues conferred a significantly reduced mitogenic activity. Moreover, all receptors were able to mediate Epo-dependant accumulation of beta-globin mRNA. The mutated receptors all induced the tyrosine phosphorylation of several cellular proteins after Epo stimulation. However, the truncated receptors induced the phosphorylation of a reduced number of proteins, suggesting that phosphorylated tyrosines of the receptor could have a role in the recruitment either of a tyrosine kinase or of tyrosine kinase substrate proteins. The receptors were all able to mediate Epo- induced activation of phosphatidylinositol 3-kinase, although truncated receptors no longer bound phosphatidylinositol 3-kinase.     

Effect of shoulder girdle strengthening on trunk alignment in patients with stroke

[Purpose] This study investigated the effect of shoulder girdle strengthening, particularly the scapular muscles, on poststroke trunk alignment. [Subjects and Methods] The study involved 30 patients with residual hemiparesis following cerebrovascular stroke. Patient assessment included measuring shoulder muscle peak torque, scapular muscles peak force, spinal lateral deviation angle, and motor functional performance. Patients were randomly allocated either to the control group or the study group and received an 18-session strengthening program including active resisted exercises for shoulder abductors and external rotators in addition to trunk control exercises. The study group received additional strengthening exercises for the scapular muscles. [Results] The two groups showed significant improvement in strength of all shoulder and scapular muscles, with higher improvement in the study group. Similarly, the lateral spinal deviation angles significantly improved in both groups, with significantly higher improvement in the study group. Transfer activity, sitting balance, upper limb functions, and hand movements significantly improved in the two groups, with higher improvement in the latter two functions in the study group. [Conclusion] Strengthening of shoulder girdle muscles, particularly scapular muscles, can significantly contribute to improving the postural alignment of the trunk in patients with poststroke hemiparesis.Key words: Stroke, Scapular muscles strengthening, Lateral trunk alignment     

A finite element study on stress distribution of two different attachment designs under implant supported overdenture

Objective

This study aimed to evaluate stress patterns generated within implant-supported mandibular overdentures retained by two different attachment types: ball and socket and locator attachments.

Materials and methods

Commercial CAD/CAM and finite element analysis software packages were utilized to construct two 3D finite element models for the two attachment types. Unilateral masticatory compressive loads of 50, 100, and 150 N were applied vertically to the overdentures, parallel to the longitudinal axes of the implants. Loads were directed toward the central fossa in the molar region of each overdenture, that linear static analysis was carried out to find the generated stresses and deformation on each part of the studied model.

Results

According to FEA results the ball attachment neck is highly stressed in comparison to the locator one. On the other hand mucosa and cortical bone received less stresses under ball and socket attachment.

Conclusions

Locator and ball and socket attachments induce equivalent stresses on bone surrounding implants. Locator attachment performance was superior to that of the ball and socket attachment in the implants, nylon caps, and overdenture. Locator attachments are highly recommended and can increase the interval between successive maintenance sessions.     

Coronary Sinus Stent: Could It Help in Refractory Chronic Stable Angina?

Refractory angina is a life-disabling disease, even with the discovery of antianginal drugs and the advances in revascularization surgically or percutaneously to improve symptoms. Over the last decade a renewal of interest in an old surgical modality of narrowing the coronary sinus has evolved. Although the surgical procedure idea was born in 1940 it was overshadowed by the development of coronary artery bypass graft and percutaneous interventions. Recently, a percutaneous approach of reducing the coronary sinus size has been developed and several clinical studies have been reported in refractory angina patients. We review the history of coronary sinus intervention, and explore coronary sinus stent possible mechanism of action, device design, and the clinical data supporting its use.     

Neoplastic lesions in CADASIL syndrome: report of an autopsied Japanese case

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is one of the most common heritable causes of stroke and dementia in adults. The gene involved in the pathogenesis of CADASIL is Notch3; in which mutations affect the number of cysteine residues in its extracellular domain, causing its accumulation in small arteries and arterioles of the affected individuals. Besides the usual neurological and vascular findings that have been well-documented in CADASIL patients, this paper additionally reports multiple neoplastic lesions that were observed in an autopsy case of CADASIL patient; that could be related to Notch3 mutation. The patient was a 62 years old male, presented with a past history of neurological manifestations, including gait disturbance and frequent convulsive attacks. He was diagnosed as CADASIL syndrome with Notch3 Arg133Cys mutation. He eventually developed hemiplegia and died of systemic convulsions. Autopsy examination revealed-besides the vascular and neurological lesions characteristic of CADASIL- multiple neoplastic lesions in the body; carcinoid tumorlet and diffuse idiopathic pulmonary neuro-endocrine cell hyperplasia (DIPNECH) in the lungs, renal cell carcinoma (RCC), prostatic adenocarcinoma (ADC) and adenomatoid tumor of the epididymis. This report describes a spectrum of neoplastic lesions that were found in a case of CADASIL patient that could be related to Notch3 gene mutations.