Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils

Hepatocyte growth factor (HGF), a heparin-binding factor, is synthesized as a single-chain inactive precursor (pro-HGF), which is converted by proteolysis to an active heterodimer (mature HGF). HGF has pleiotropic activities and has been implicated in the regulation of mitogenesis, motogenesis, and morphogenesis of epithelial and endothelial cells. As polymorphonuclear neutrophils (PMNs) secrete numerous cytokines involved in the modulation of local inflammation, we investigated their ability to produce HGF. We found that HGF was stored in secretory vesicles and in gelatinase/specific granules. This intracellular stock was rapidly mobilized by degranulation when neutrophils were stimulated with phorbol myristate acetate or N-formylmethionyl-leucyl-phenylalanine. Cycloheximide did not affect the release of HGF. Moreover, HGF messenger RNA and protein expression was found in bone marrow myeloid cells, suggesting that HGF synthesis likely occurs during PMN maturation. In mature circulating PMNs, intracellular HGF was in the pro-HGF form, whereas the HGF secreted by degranulation was the mature form. Furthermore, PMNs pretreated with diisopropyl fluorophosphate only released the pro-HGF form, suggesting that PMN-derived serine protease(s) are involved in the proteolytic process. We also obtained evidence that secreted mature HGF binds PMN-derived glycosaminoglycans (probably heparan sulfate). These findings suggest that PMNs infiltrating damaged tissues may modulate local wound healing and repair through the production of HGF, a major mediator of tissue regeneration.     

Axillary Hodgkin's disease in manual workers.

Between 1965 and 1974, 16 patients were clinically staged as having unique axillary localizations of Hodgkin's disease. Sex ratio (4.3), mean age (40.8 years) and professional occupations (12 out of the 16 patients were engaged in manual work) were significantly different from that of all patients observed during the same period. These facts lead us to suppose the existence of a link between manual work and initial axillary localizations.     

H ferritin knockout mice: a model of hyperferritinemia in the absence of iron overload

Ferritin, the iron-storing molecule, is made by the assembly of various proportions of 2 different H and L subunits into a 24-mer protein shell. These heteropolymers have distinct physicochemical properties, owing to the ferroxidase activity of the H subunit, which is necessary for iron uptake by the ferritin molecule, and the ability of the L subunit to facilitate iron core formation inside the protein shell. It has previously been shown that H ferritin is indispensable for normal development, since inactivation of the H ferritin gene by homologous recombination in mice is lethal at an early stage during embryonic development. Here the phenotypic analysis of the mice heterozygous for the H ferritin gene (Fth(+/-) mice) is reported, and differences in gene regulation between the 2 subunits are shown. The heterozygous Fth(+/-) mice were healthy and fertile and did not present any apparent abnormalities. Although they had iron-overloaded spleens at the adult stage, this is identical to what is observed in normal Fth(+/+) mice. However, these heterozygous mice had slightly elevated tissue L ferritin content and 7- to 10-fold more L ferritin in the serum than normal mice, but their serum iron remained unchanged. H ferritin synthesis from the remaining allele was not up-regulated. This probably results from subtle changes in the intracellular labile iron pool, which would stimulate L ferritin but not H ferritin synthesis. These results raise the possibility that reduced H ferritin expression might be responsible for unexplained human cases of hyperferritinemia in the absence of iron overload where the hereditary hyperferritinemia-cataract syndrome has been excluded. (Blood. 2001;98:525-532)     

Association of Alzheimer's disease onset with ginkgo biloba and other symptomatic cognitive treatments in a population of women aged 75 years and older from the EPIDOS study

BACKGROUND: Peripheral C4A treatment (cerebral and peripheral vasotherapeutics) and especially Ginkgo biloba extracts are prescribed for a number of symptoms, particularly memory impairment, in elderly patients. It is postulated that because of its pharmacological actions, this treatment could prevent the decline of cognitive function, but no studies have been published to date to test its efficacy in prevention of Alzheimer's disease. The potential association between use of C4A treatments, in particular EGb 761 (standardized Ginkgo biloba extracts), and dementia of the Alzheimer type was investigated. METHODS: A case-control study was nested in a cohort of 1462 community-dwelling elderly women aged over 75 years. Sixty-nine women with Alzheimer-type dementia were compared with 345 paired women whose cognitive function remained normal. This study involved women whose cognitive function was evaluated at baseline by use of Pfeiffer's test and whose medication history was taken. The onset of cognitive impairment was investigated over a 7-year follow-up period. In order to study the factors associated with the onset of dementia, the data concerning women with a score of > or = 8 on Pfeiffer's test at inclusion, indicating normal cognitive function, were analyzed. RESULTS: A multivariate analysis including potential confounding factors showed that fewer women who developed Alzheimer's dementia had been prescribed C4A treatment (including EGb 761) for at least 2 years (odds ratio = 0.31, 95% confidence interval = 0.12-0.82, p =.018). Figures for EGb 761 alone were similar but did not reach statistical significance (odds ratio = 0.38, 95% confidence interval = 0.08-1.76, p =.22). CONCLUSION: These results suggest that C4A treatment may reduce the risk of developing Alzheimer's dementia in elderly women. The potential preventive effect of C4A treatments, including EGb 761, requires further examination. To establish a causal relationship, these findings have to be confirmed with prospective studies.     

Prostate-specific antigen doubling time before onset of chemotherapy as a predictor of survival for hormone-refractory prostate cancer patients.

BACKGROUND: We evaluated the possible use of prostate-specific antigen doubling time (PSA-DT) before chemotherapy initiation as a surrogate marker of survival in hormone-refractory prostate cancer (HRPC) patients. PATIENTS AND METHODS: Data from 250 consecutive metastatic HRPC patients treated with chemotherapy between February 2000 and November 2006 were retrospectively analysed. At least three PSA assays were required within 3 months before chemotherapy. PSA-DT was calculated as ln 2 divided by the slope of the log PSA line, and the difference between two log PSA levels was divided by the time interval. The primary endpoint was overall survival (OS). Survival rates according to PSA-DT were stratified on chemotherapy regimen. Multivariate Cox regression analysis was performed to isolate the impact of PSA-DT on OS, controlling for associate prognostic covariates. RESULTS: Patients received docetaxel- (82%) or mitoxantrone-based chemotherapy. The median PSA-DT was 45 days (range 4.7-1108 days). There were 174 deaths (70%). The median survival was 16.5 months (95% confidence interval [CI] = 12.5-20.5) and 26.4 months (95% CI = 20.3-32.4) for patients with a PSA-DT < 45 and > or =45 days, respectively. In the multivariate setting, the adjusted hazard ratio (HR) was 1.39 (95% CI = 1.03-1.89; P = 0.04), stratified by chemotherapy regimen. CONCLUSION: A short PSA-DT before onset of chemotherapy in HRPC patients was associated with an increased risk of death. This could be useful as a stratification parameter in trials with new drugs in a metastatic setting.     

pS2 and response to adjuvant hormone therapy in primary breast cancer.

We reviewed 319 primary breast tumours for cytosolic pS2 content, with a median follow-up of 6 years. pS2 status correlated positively with oestradiol and progesterone receptors and negatively with Scarff, Bloom and Richardson grade. pS2 positivity was associated with longer overall survival, particularly in patients who received hormone therapy, in whom pS2 status was also predictive of the response to therapy.     

Development of the pre-school child: the validation of a psychomotor screen, and the influence of the home environment on psychomotor development

ABSTRACT. The present study was designed to validate and standardize a short psychomotor screening test on Australian four-year-old-preschool children and to assess their home environment using Caldwell's HOME Inventory. The Adelaide Psychomotor Screen (APS) is a short, 10--15 minute screening test which uses 13 separate items to assess "General" development, "Gross Motor" development, "Social/Emotional Behaviour" and "Speech".
In the area of "General" development, 12 children screened as "abnormal" and 54 children screened as "normal" were further assessed by a psychologist on the McCarthy Scales of Children's Abilities. There was a high correlation between the APS "General" scores and the McCarthy (General Cognitive Index) scores (r = 0.75, p<0.001 for the younger children, and r = 0,90, p <0.001 for the older children).
Caldwell's HOME Inventory takes an hour to complete, and involves a visit by the assessor to each home. The correlation between the HOME total scores and the McCarthy (General Cognitive Index) scores was r =0.06, p < 0.001. It is suggested that the HOME Inventory may be more valuable as a predictor of a child's future development than an index of his present developmental status.
It is suggested that nurses and teachers used the APS as a screening test of the individual child, and use the HOME inventory as an assessment of the home environment.     

Management of cleft lip and palate in university hospital of Rouen

Cleft lips and cleft palates are managed in the department of Pediatric surgery in Rouen for the last 30 years. From the antenatal diagnosis, the parents got in touch with the surgeon who will coordinate this management. Around thirty new patients are treated every year. The chronology of the treatment is of "classic" manner. The cleft lip is repaired at about 3 weeks of age and the palatoplasty is performed after the age of 1 year. In view to maintain the intimacy of the consultation we did not institute multidisciplinary consultations. The other members of the interdisciplinary team will intervene during the follow up depending on the form of the cleft and the encountered problems. The information and the files circulate freely and are discussed together.     

Colonization of the oral cavity by Candida species: risk factors in long-term geriatric care

The population of elderly people in hospitals for long-term geriatric care presents many risk factors for nosocomial infection by Candida species. The aim of this work was to reduce the risk of C. albicans nosocomial infections starting from colonization of the oral cavity. The population of concern was the patients in long-stay geriatrics units; a sample of 110 people was selected by drawing lots. The clinical and biological parameters of each patient included in the study were recorded. The oral cavity was colonized by Candida spp in 67% of cases. The distribution of the strains showed that C. albicans was the most frequently identified strain, followed by C. glabrata; of the 73 patients with at least one strain of Candida spp., 47 had a clinically diagnosed candidiasis (64.4%). The wearing of dentures was not statistically linked with the development of oral candidiasis. Detecting which patients have been colonized, identifying the risk factors and applying preventive measures should reduce the probability of elderly people falling into the vicious circle of infection-malnutrition-immune-depression.