Stimulation of tyrosine phosphorylation after ligation of beta7 and beta1 integrins on human B cells

B lymphocytes express several members of the integrin family of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. In addition to beta1 integrins, predominantly alpha4 beta1, mature B cells also express alpha4 beta7, which is a receptor for vascular cell adhesion molecule-1 and fibronectin, and is also involved in the homing of B cells to mucosal sites through binding to a third ligand, mucosal address in cell adhesion molecule-1. Here we describe that crosslinking of alpha4 beta7 integrins on B cell lines and normal tonsillar B cells, induces tyrosine phosphorylation of multiple substrates of 105-130 kD, indicating that beta7 integrin plays a role as signaling molecule in B cells. This pattern of phosphorylated proteins was very similar to that induced following ligation of alpha4 beta1. Interestingly, ligation of alpha5 beta1 or alpha6 beta1 also stimulated the 105-125 kD group of phosphorylated proteins, whereas ligation of beta2 integrins did not. The focal adhesion tyrosine kinase p125FAK was identified as one of these substrates. Beta1 or beta7 mediated tyrosine phosphorylations were markedly decreased when the microfilament assembly was inhibited by cytochalasin B. These results suggest that intracellular signals initiated by different integrins in B cells may converge, to similar cytoskeleton-dependent tyrosine phosphorylated proteins.     

Informant ratings of cognitive decline of elderly people: relationship to longitudinal change on cognitive tests

Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline.     

Defects in type IIA von Willebrand disease: a cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX

Type IIA von Willebrand disease (vWD) is characterized by the loss of high and intermediate weight multimers of von Willebrand factor (vWF) from plasma. The 3' end of exon 28 in the vWF gene from four type IIA vWD patients was amplified by the polymerase chain reaction, cloned and sequenced. Sequencing identified two potential missense mutations resulting in the amino acid substitutions Arg 834-->Gln and Glu 875-->Lys in the mature vWF subunit within an area of vWF where mutations in type IIA vWD have been reported. Neither of these amino acid substitutions was found in over 100 normal alleles tested by allele specific oligonucleotide hybridization. A polymorphism (Val 802-->Leu) was identified in another patient. Other areas of exon 28 were analysed by denaturing gradient gel electrophoresis (DGGE) and DNA from one patient demonstrated an irregular DGGE pattern on the 5' end of the exon. Sequencing demonstrated an amino acid substitution of an arginine for cysteine at position 509 adjacent to an area of vWF where defects associated with type IIB vWD have been found. This substitution was not found in 100 normal chromosomes tested by restriction enzyme digestion. The Cys 509-->Arg substitution eliminates an intramolecular disulphide bridge formed by Cys 509 and Cys 695 which is important to maintain the configuration of vWF functional domains that interact with platelet glycoprotein Ib-IX.     

CARDIAC AUTONOMIC NEUROPATHY IN DIABETES MELLITUS

Forty-eight out of 95 patients with diabetes mellitus, who were asymptomatic for autonomic nervous system affections, were evaluated with 3 bedside tests to detect subclinical cardiac neuropathy. There were 25 males and 23 females in the age range of 10-60 years. The three tests carried out were, heart rate response to Valsalva manoeuvre, heart rate variation during deep breathing, and systolic blood pressure fall in response to standing. Of these 48 patients, 15 (31.3%) had evidence of neuropathy. Abnormality of the parasympathetic division was found in 13 patients and the remaining 2 patients had borderline affection. Three patients had evidence of a combined parasympathetic and sympathetic involvement. Sympathetic affection alone was not detected in any patient. Increased incidence was seen in older age group. Autonomic neuropathy was more common in patients who had the disease for over 5 years. There was no correlation with the sex of the patient or with metabolic control of diabetes.KEY WORDS: Autonomic nervous system diseases, Diabetes Mellitus, Neuropathy     

COMPARATIVE EVALUATION OF NO-SCALPEL VASECTOMY AND STANDARD INCISIONAL VASECTOMY

No-scalpel vasectomy employs a refined method of dissection and delivery of the vas deferens. We compared no-scalpel vasectomy with standard incisional vasectomy in 176 patients over a 33 month period. The haemorrhage rate was 1.08 per cent for no-scalpel vasectomy compared with 11.9 per cent for standard vasectomy (p < 0.005). The infection rate was 3.26 per cent for no-scalpel vasectomy as against 14.28 per cent for standard vasectomy (p < 0.01). There was a 37.5 per cent reduction in operating time and a substantial reduction in pain during and after the procedure when no-scalpel vasectomy was performed and also there was no failure of vasectomy. No-scalpel vasectomy is a satisfactory alternative to standard vasectomy with fewer complications and increased patient acceptability.KEYWORDS: Male sterilization, Vasectomy