Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1-antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.     

Fine mapping of the locus for nevoid basal cell carcinoma syndrome on chromosome 9q

The nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized primarily by multiple basal cell carcinomas, odontogenic keratocysts, and pits of the palms and soles. Tumor deletion studies and linkage analysis in Caucasians have revealed that the gene is on chromosome 9q. To further refine the location of the nevoid basal cell carcinoma syndrome locus, we tested linkage to this region in three families. Evaluation of recombinants suggested that the nevoid basal cell carcinoma syndrome locus lies in the interval defined distally by D9S127. Our data, together with existing published data defining D9S12 as a proximal flanking marker, refine the location of nevoid basal cell carcinoma syndrome to an 8.3-cM interval. Two of the families studied were African-American and show a notable variation in phenotypic expression in which affected individuals developed few skin cancers. However, despite clinical heterogeneity, our data are consistent with the hypothesis that the same locus is involved in these African-American families.     

Endogenous opioids modulate allograft rejection time in mice: possible relation with Th1/Th2 cytokines

Massive enlargement of an extracerebral cavernous malformation and extension across tissue planes is very uncommon. The authors present the case of a 49-year-old woman with a giant cavernous malformation in the left frontotemporal area. It progressively enlarged during several decades, extended through the calvaria to the extradural space, and was surgically treated. The lesion may have originated in the soft tissue or the skull. The locations of cavernous malformations in various parts of the body are reviewed and their mechanisms of growth are discussed. Surgical excision is the treatment of choice.     

Differences in self reported morbidity by educational level: a comparison of 11 western European countries

Raman and infrared spectra were examined for guanosine 5'-diphosphate (GDP) and guanosine 5'-triphosphate (GTP) in aqueous solution. The vibrational modes were assigned on the basis of isotopic frequency shifts and relative intensities in the Raman and infrared spectra. The observed frequency shifts on 18O isotope labeling made it possible to identify the bands from each phosphate group (alpha, beta, gamma). Frequency shifts were observed as Mg2+ complexes with GDP and GTP. The results suggested that Mg2+ binds to GDP in a bidentate manner to the alpha, beta P[symbol: see text]O bonds and in a tridentate manner to the alpha, beta and gamma P[symbol: see text]O bonds of Mg.GTP. The results indicate that structure of Mg2+ coordinated to GTP in aqueous solution differs somewhat to that found for Mg.ATP.     

Facilitating condom use with clients during commercial sex in Nevada's legal brothels

OBJECTIVES: This study examined condom use in legal Nevada brothels. METHODS: Forty female prostitutes in two brothels were interviewed about client resistance to condoms and techniques for facilitating condom use. RESULTS: Of 3290 clients in the previous month, 2.7% (95% confidence interval [CI] = 2.2%,3.4%) were reluctant to use condoms. Of these individuals, 72% ultimately used condoms, while 12% chose nonpenetrative sex without condoms. The remaining 16% left the brothels without services. Condom use rates were markedly lower with nonpaying sex partners (lowers) than with clients. CONCLUSIONS: Brothel prostitutes may be at greater risk for acquiring HIV and other sexually transmitted diseases from lovers than from clients.     

Splitting hairs: dissecting roles of signaling systems in epidermal development

A case of hepatic portal venous gas following intestinal ileus in a critically ill patient in the intensive care unit, who went on to have a successful outcome, is described. Although hepatic portal venous gas (HPVG) is usually associated with an abdominal catastrophe and portends a poor clinical outcome, there are a number of benign causes of HPVG. The pathophysiological processes such as gut bacterial translocation and altered intestinal permeability that may occur as a paraphenomenon in the setting of HPVG are discussed.     

The late results of the surgical treatment of perforated gastroduodenal ulcers in young people

The article is devoted to surgical treatment of perforating gastroduodenal ulcers. An investigation of remote results of palliative and radical interventions for the perforation of the stomach and duodenum in patients of young age has shown that recurrent ulcers after suturing the perforation take place in 67.2% of the people operated upon against 21% of those subjected to bilateral truncal subdiaphragmatic vagotomy with pyloroplasty. A conclusion is made that for perforating ulcers it is expedient to perform radical operative interventions as a bilateral truncal subdiaphragmatic vagotomy with pyloroplasty.     

A novel insertional mutation in loricrin in Vohwinkel's Keratoderma

A mutation in the gene encoding loricrin has recently been reported in a subset of patients with Vohwinkel's Keratoderma manifesting an associated ichthyosiform dermatosis. We have studied a further kindred with this clinical phenotype. Microsatellite marker analysis was consistent with linkage to chromosome 1q21 and direct sequencing of loricrin identified a heterozygous mutation with an insertion of a T residue at codon 209. This mutation is predicted to produce a mutant protein with a frameshift of its terminal 107 amino acids and to be 22 amino acids longer than the wild-type protein due to a delayed termination codon. The only previously reported mutation is a G insertion producing a frameshift after codon 231. The novel mutation we report is likely to have a similar functional effect on cornified envelope formation, with disturbance of transglutaminase-mediated cross-linking of envelope components, and serves to confirm the predicted role of insertional mutations in Vohwinkel's Keratoderma associated with ichthyosis.