Constitutive secretion of the granule chymase mouse mast cell protease-1 and the chemokine, CCL2, by mucosal mast cell homologues

BACKGROUND: The mucosal mast cell (MMC) granule-specific beta-chymase, mouse mast cell protease-1 (mMCP-1), is released systemically into the bloodstream early in nematode infection before parasite-specific IgE responses develop and TGF-beta1 induces constitutive release of mMCP-1 by homologues of MMC in vitro. Intraepithelial MMC may also express the chemokine CCL2 (monocyte chemotactic protein-1) during nematode infection but the expression of this chemokine by MMC homologues has not been investigated. OBJECTIVE: To investigate the expression and to compare the mechanisms of constitutive release of the chymase, mMCP-1, and the chemokine, CCL2. METHODS: MMC homologues were generated by culturing bone marrow cells in the presence of TGF-beta1, IL-3, IL-9 and stem cell factor (SCF). The intracellular distribution of mMCP-1 and CCL2 was examined by confocal microscopy. The involvement of the Golgi complex and of protein synthesis in the constitutive release of mMCP-1 and CCL2 was investigated using the Golgi-disrupting agent brefeldin A and cycloheximide to block protein synthesis. Secreted analytes were quantified by ELISA. RESULTS: mMCP-1 colocalized with Golgi matrix protein 130 but was most abundant in the granules, whereas CCL2 was not found in the granules but appeared to be located uniquely in the Golgi complex. Extracellular release of mMCP-1 was significantly inhibited ( approximately 40%) by cycloheximide and by the Golgi-disrupting agent brefeldin A, indicating both continuous protein synthesis and transportation via the Golgi complex are required for optimal mMCP-1 secretion. A similar but more marked inhibitory effect with both compounds was demonstrated on the constitutive secretion of CCL2. CONCLUSION: The culture conditions that promote mMCP-1 expression and release by MMC homologues also promote the expression and release of CCL2. Constitutive release involves de novo protein synthesis and requires a functional Golgi complex, suggesting that similar mechanisms of extracellular secretion operate for both mediators.     

Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Possible role of alpha-2-noradrenergic receptors in modulation of sexual behavior in female guinea pigs

These studies examine whether alpha 1-noradrenergic receptor stimulation alone is sufficient to facilitate lordosis behavior in ovariectomized, estrogen-primed female guinea pigs and to what extent alpha 2-noradrenergic receptors are involved in this steroid-dependent behavior. Neither of the alpha 1-agonists, phenylephrine or methoxamine, significantly facilitated lordosis in ovariectomized females primed with 10 micrograms of estradiol benzoate for 1 or 3 days. Animals exhibiting estrogen plus clonidine-facilitated lordosis showed a decrease in the behavior when given one of two alpha 2-antagonists (yohimbine or idazoxan). Idazoxan also attenuated lordosis in animals given estrogen plus progesterone. These findings, in combination with previous findings (that specific alpha 1-antagonists block lordosis), suggest that alpha 2-receptors, in addition to alpha 1-receptors play a role in modulation of lordosis behavior.     

Therapist features in sexual offender treatment: their reliable identification and influence on behaviour change

In the first of the two studies reported here, we established that trained judges could reliably identify 18 therapist features that occurred with reasonable frequency. In the second study 17 of these features were examined to determine how well they related to changes in sexual offenders with treatment. Five videotapes from each of five different prison programs were rated for the presence of these 17 features and correlational analyses examined their relationship with changes in 44 measures of treatment targets. The primary findings indicated that empathy and warmth displayed by the therapists and their directive and rewarding behaviours, were the features that most strongly predicted therapeutic benefits. The results are discussed in terms of their clinical and research implications. Copyright © 2002 John Wiley & Sons, Ltd.     

Familial and sporadic hyperinsulinism: histopathologic findings and segregation analysis support a single autosomal recessive disorder

We evaluated the possible genetic contribution to hyperinsulinism in a series of patients seen during the past 15 years. Of 26 families, 5 (19%) had more than one child affected (multiplex family). There were no apparent differences between patients in the 5 multiplex and 21 simplex families, clinically, biochemically, or on histologic examination of the pancreatic specimens. The families studied had a total of 63 offspring; the 26 index patients had 37 siblings, 6 of whom were affected. After four patients with hyperinsulinism caused by adenoma were excluded from the study, segregation analysis was carried out to test the data for agreement with results expected if familial and isolated hyperinsulinism represented a single disease with recessive mode of inheritance and a segregation ratio of 0.25. Excellent agreement was found between the observed number of affected siblings (20) and the expected number (19.65), with a segregation ratio of 0.254. The results were consistent with the hypothesis that in most or all cases, hyperinsulinism is inherited as an autosomal recessive disease. There was no evidence of distinct familial and sporadic types.     

Emerging Patterns in Adolescent Drug Use: The Belfast Youth Development Study 2000-2002

This paper reports the findings from the first 2 years of the Belfast Youth Development Study. The Belfast Youth Development Study is a 5-year longitudinal investigation of the onset and development of adolescent drug using behaviours, the findings of the first 2 years from the study in relation to drug use patterns among the young people participating in the research are reported here. The findings show that while the majority of young people have not yet used an illicit substance, the study has seen a substantial increase in the numbers using such substances between year 1 and year 2. Boys still make up the majority of drug users in this period but there has been a substantial increase in the number of girls using illicit drugs and, more generally, an increase in the frequency of use among all those using such substances during this period.     

Studies on the endogenous flora of the human breast

Identification of the endogenous microbiological flora of the human breast and its role in breast infections following subglandular augmentation or reduction mammaplasty was undertaken. A total of 231 cultures were performed on 59 breasts in 30 patients. Patients were followed for 12 months. No fungus was cultured from any specimen. Of the breasts cultured 53% were positive for coagulase-negative staphylococcus. Other aerobes found included diphtheroids, lactobacillus, D-enterococcus, micrococcus, and alpha-hemolytic streptococcus. Propionibacterium acne was the most frequent anaerobic bacteria cultured. Other anaerobes included peptococcus and clostridium sporogenes. There was no correlation with respect to the type of bacterium and the depth within the breast where the culture specimens were taken. Postoperative wound infections developed in 2 of 19 patients undergoing reduction mammaplasty. Bacteria identical to those cultured at the time of surgery were again cultured from the wound. Twenty subglandular augmentation mammaplasties were performed with a 25% capsular rate at one year. Two capsules were associated with no bacterial growth at the time of mammaplasty surgery, whereas three were associated with coagulase-negative staphylococcus, Propionibacterium acne, and diphtheroids, respectively. Of the 15 breasts with no capsular contracture after one year, operative culture revealed coagulase-negative staphylococcus in 8 and no bacterial growth in 7. Even breast tissue located deep within the gland away from the nipple contains a flora that is similar to that of normal skin. Cases of infection in which the endogenous bacteria were correlated with later infection was documented.     

A prospective randomized trial of laparoscopic versus open appendectomy.

BACKGROUND. Laparoscopic appendectomy is feasible, but whether it confers any advantage to patients with acute appendicitis is not known. We performed a randomized controlled trial to compare results of laparoscopic and open appendectomy in patients with signs and symptoms suggesting acute appendicitis who were seen by one surgical team. METHODS. Sixty-two consecutive patients were randomized, 30 to laparoscopy and 32 to a classical open appendectomy. Postoperative recovery, complications, and return to normal activities were compared in the two groups. RESULTS. The laparoscopy group were discharged earlier (2.5 vs 3.8 days, p less than 0.01). Postoperative complications were more frequent after open appendectomy. Follow-up showed less pain, shorter bed stay at home, and faster return to work and sport after laparoscopic appendectomy. CONCLUSIONS. This prospective randomized study shows that laparoscopic appendectomy is superior to open appendectomy in terms of hospital stay, postoperative complications, and return to normal activities and is recommended as the approach of choice in the management of acute appendicitis.