Identification of 130 kDa cell surface LDL-binding protein from smooth muscle cells as a partially processed T-cadherin precursor

Atypical cell surface lipoprotein-binding proteins of 105 kDa and 130 kDa are present in membranes of vascular smooth muscle cells. We recently identified the 105 kDa protein from human aortic media as T-cadherin, an unusual glycosylphosphatidylinositol (GPI)-anchored member of the cadherin family of cell adhesion proteins. The goal of the present study was to determine the identity of 130 kDa lipoprotein-binding protein of smooth muscle cells. We applied different approaches that included protein sequencing of purified protein from human aortic media, the use of human T-cadherin peptide-specific antisera, and enzymatic treatment of cultured cells with trypsin and GPI-specific phospholipase C. Our results indicate that the 130 kDa protein is a partially processed form of T-cadherin which is attached to the membrane surface of smooth muscle cells via a GPI anchor and contains uncleaved N-terminal propeptide sequence. Our data disclose that, in contrast to classical cadherins, T-cadherin is expressed on the cell surface in both its precursor (130 kDa) and mature (105 kDa) forms.     

Primary ciliary dyskinesia (the immotile cilia syndrome)

OBJECTIVE: The purpose of this review is to familiarize the reader with the genetic aspects, clinical manifestations, diagnostic techniques and management of the primary ciliary dyskinesia syndrome. Further, this article illustrates some unusual features of this syndrome and discusses some speculative hypotheses concerning its pathogenesis and clinical presentation. DATA SOURCES: The bibliography includes references in English as well as some references of historical interest in German. Both human and veterinary literature are quoted. Sources included computerized bibliographic searches of recent literature and reviews of literature. STUDY SELECTION: Selection of papers was made based on their historic importance in the definition and characterization of the disease, and on reviews of large bodies of novel or interesting information. Some review papers were not included to avoid repetition. RESULTS: Although the incidence of primary ciliary dyskinesia is low, the inclusion of this condition in the differential diagnosis of chronic and recurrent sinobronchial disease in children and older individuals is very common. Primary ciliary dyskinesia should be suspected in individuals who present chronic respiratory symptoms already in the neonatal period, develop profuse, chronic mucopurulent rhinorrhea, and chronic otitis media and sinusitis. Chronic cough, obstructive lung disease, and bronchorrhea associated with the aforementioned manifestations should also make clinicians suspect this syndrome. Male sterility is almost universally present and situs inversus is present in 50% of affected persons. The diagnosis of primary ciliary dyskinesia is clinical and is confirmed by studies of ciliary motility and ultrastructure of the respiratory mucosa. Management is directed to microbial suppression by frequent antibiotic administration, and to clearing of retained secretions. CONCLUSIONS: The diagnosis of primary ciliary dyskinesia requires familiarity with the clinical picture and the specific techniques of identification. Although the basic mechanism of disease is known, the molecular genetics of primary ciliary dyskinesia and the causes for the phenotypic variability remain to be explained. Future research should be directed to the identification of the gene(s) responsible for the manifestations of the disease and to effective methods of activation, in vivo, of dysfunctional cilia.     

Urodynamic picture in high spinal cord ischemia, induced by addictive use of cocaine. Report of a case

Since in vitro experiments had excluded interactions between Fe-gluconate (Fe-gluc) and magnesium-L-aspartate hydrochloride (MAH) in aqueous solutions the present in vivo studies seemed to be justified. Animal studies: Rats were kept on magnesium-(Mg)- and iron-(Fe)- sufficient and deficient diets. The intragastral administration of Fe-gluc significantly increased plasma Fe after 3 h, either given alone, or in combination with MAH (inducing hypermagnesemia). Same results were obtained when fortified diets were offered to Fe/Mg-deficient animals. Human studies: The combination of Fe-gluc (2 x 50 mg Fe per day, per os) plus MAH (2 x 7.5 mmol Mg per day, p.o.) was well tolerated by healthy volunteers. Single dose experiments revealed that Fe-gluc alone and in combination with MAH increased plasma Fe levels during 3 h to the same extent. Two groups of pregnant women with moderately reduced hemoglobin levels either received Fe-gluc (out-patients) or its combination with MAH (at least temporarily hospitalised because of preterm labor). Treatments were well tolerated. Hemoglobin levels did not further decrease, as expected without Fe supplements, during the course of pregnancy, thus indicating the therapeutic availability of the electrolytes in both study groups. Progesterone-induced constipation is frequently observed during pregnancy; hence stool softening reported by 50% of the women receiving Fe-gluc plus MAH (versus 33% in the Fe-gluc group) can be regarded as desirable effect. It is concluded that MAH does not interfere with the enteral absorption of Fe-gluc when both electrolytes are orally administered together. Taking both electrolytes together instead of 2 to 3 h apart from each other, as actually recommended, means a less complicated dosage regimen and probably improves compliance.     

Relation between insulin-like growth factor-I concentrations, osteoarthritis, bone density, and fractures in the general population: the Chingford study

OBJECTIVE: To assess the association between serum insulin-like growth factor-I (IGF-1) concentrations and osteoarthritis, and bone mineral density, and fractures in a large group of middle aged women from the general population. METHODS: 761 women aged 44-64 years from the Chingford study had serum IGF-I concentrations measured; hand, hip, spine, and anteroposterior weight bearing knee radiographs taken; and dual energy x ray absorptiometry (DEXA) scans of the hip and spine. X rays were scored using the Kellgren and Lawrence system. In addition knee x rays were scored using a standard atlas for individual features of osteophytes and joint space narrowing (both graded 0-3). IGF-I concentrations were adjusted for the effects of age. RESULTS: In the osteoarthritis analysis results were compared to a constant group of 155 subjects with no evidence of osteoarthritis at any site. There was no significant difference in serum IGF-I between these subjects and 606 subjects with osteoarthritis at any site. When individual sites were analysed, serum IGF-I was higher in those cases with more severe bilateral knee osteoarthritis and in those with distal interphalangeal (DIP) joint disease. There was no significant association between serum IGF-I and other forms of osteoarthritis or milder forms of knee osteoarthritis. There was no correlation between IGF-I concentrations and bone mineral density at the spine or hip, nor any difference between IGF-I concentrations in subjects with and without a history of non-traumatic fracture [22.8 (SD 6.6) v 23.1 (SD 6.6) nmol litre-1, P = 0.6] CONCLUSIONS: There is a modest association between IGF-I concentrations and the development of DIP osteoarthritis and more severe or bilateral knee joint osteoarthritis in women from the normal population, but no association with other forms of osteoarthritis, bone density, or fractures.