Human platelet glycoprotein V: its role in enhancing expression of the glycoprotein Ib receptor

Platelet adhesion to an injured blood vessel wall is a critical initiating step in hemostasis mediated by a four member receptor complex (glycoprotein Ib/V/IX) interacting with plasma von Willebrand factor (vWF). The function of the GPV subunit within this complex is presently undefined. To study the role of glycoprotein (GP) V within the GPIb receptor complex, we transfected the GPV subunit gene into a hematopoietic cell line that constitutively expresses the other three subunits (human erythroleukemia [HEL] cells). Using flow cytometry, we found transfected GPV was surface expressed in HEL cells; this, in turn, led to increased surface expression of the ligand-binding GPIb alpha and GPIX subunits. Radioligand binding assays showed that GPV- transfected HEL cells bound more vWF than their non- or mock- transfected counterparts. We employed confocal microscopy of GPV- transfected HEL cells to show that GPV colocalizes with GPIb alpha on the cell surface. These findings suggest that the GPV subunit plays a role within the GPIb receptor complex by enhancing Ib alpha surface expression.     

Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families

In communities with high rates of consanguinity and consequently high prevalence of recessive phenotypes, homozygosity mapping with SNP arrays is an effective approach for gene discovery. In 20 Palestinian kindreds with prelingual nonsyndromic hearing loss, we generated homozygosity profiles reflecting linkage to the phenotype. Family sizes ranged from small nuclear families with two affected children, one unaffected sibling, and parents to multigenerational kindreds with 12 affected relatives. By including unaffected parents and siblings and screening 250 K SNP arrays, even small nuclear families yielded informative profiles. In 14 families, we identified the allele responsible for hearing loss by screening a single candidate gene in the longest homozygous region. Novel alleles included missense, nonsense, and splice site mutations of CDH23, MYO7A, MYO15A, OTOF, PJVK, Pendrin/SLC26A4, TECTA, TMHS, and TMPRSS3, and a large genomic deletion of Otoancorin (OTOA). All point mutations were rare in the Palestinian population (zero carriers in 288 unrelated controls); the carrier frequency of the OTOA genomic deletion was 1%. In six families, we identified five genomic regions likely to harbor novel genes for human hearing loss on chromosomes 1p13.3 (DFNB82), 9p23–p21.2/p13.3–q21.13 (DFNB83), 12q14.3–q21.2 (DFNB84; two families), 14q23.1–q31.1, and 17p12–q11.2 (DFNB85).     

Gastrointestinal bleeding: dyspeptic symptoms and clinical course in relation to use of non-steroidal antiinflammatory drugs

To study the symptoms of NSAID-associated gastroduodenal bleeding, 94 patients (median age 71 years, range 19-90), were included in a prospective, clinical trial where hematemesis or melena from gastroduodenal ulceration or haemorrhagic/erosive gastritis were the inclusion criteria. NSAID use within one month was studied in relation to subjective symptoms prior to admission and to clinical course of the episode. Significantly fewer of the NSAID users (n = 54) than the non-users (n = 40) had experienced prior peptic ulceration or dyspeptic symptoms. Otherwise, no differences were seen between users and non-users, as regards pre-admission epigastric pain, heartburn or nausea. Also, the clinical course was similar in the two groups. We also found sporadic and regular NSAID use to be similar in this respect. These data do not support the alleged masking of ulcer symptoms by NSAIDs in bleeding ulcers.     

Gastrointestinal bleeding associated with the use of non-steroidal,anti-inflammatory drugs—symptomatology and clinical course

The symptoms associated with admission for gastrointestinal haemorrhage were studied in relation to the intake of non-steroidal, anti-inflammatory drugs (NSAIDs) within fourteen days prior to admission. In a prospective, two-year study we included only those with bleeding due to gastroduodenal ulcers or haemorrhagic erosive gastritis. In 94 patients with a median age of 74 years, NSAID use was stated in 54, but the symptoms in these subjects (degree of epigastric pain, nausea or heartburn) were no different from those without previous NSAID use. Correspondingly, no difference was seen as to the clinical course of the bleeding.     

Gastrointestinal bleeding associated with the use of non-steroidal,anti-inflammatory drugs—symptomatology and clinical course

The symptoms associated with admission for gastrointestinal haemorrhage were studied in relation to the intake of non-steroidal, anti-inflammatory drugs (NSAIDs) within fourteen days prior to admission. In a prospective, two-year study we included only those with bleeding due to gastroduodenal ulcers or haemorrhagic erosive gastritis. In 94 patients with a median age of 74 years, NSAID use was stated in 54, but the symptoms in these subjects (degree of epigastric pain, nausea or heartburn) were no different from those without previous NSAID use. Correspondingly, no difference was seen as to the clinical course of the bleeding.     

The relationship between plasma iron and plasma iron turnover in the rat

Plasma iron turnover has been evaluated in the growing rat. Consistent data were obtained with the intravenous injection of radioiron in the form of ferrous sulfate or ferric citrate. Plasma iron turnover changed as a function of plasma iron concentration. Only part of this effect in the rat was due to the different rates of clearance of mono-and differic transferrin, the latter having a higher iron delivery rate in vivo. An additional effect was shown to relate to the rate of red cell production. With decreased production, the effect of plasma iron on plasma iron turnover was reduced, whereas with increased erythropoiesis there was an additional increment in plasma iron turnover for any increase in plasma iron. Since this effect was observed when increased iron demands were due to an increase in erythroid precursors in the marrow but not in the circulating blood, it is attributed to limitations in iron flow to the marrow. This suggests that erythroid marrow activity and the adequacy of iron supply when studied by ferrokinetic techniques can best be defined by the response curve relating plasma iron concentration to plasma iron turnover.