Junctional adhesion molecule-A is co-expressed with HER2 in breast tumors and acts as a novel regulator of HER2 protein degradation and signaling.

Junctional adhesion molecule-A (JAM-A) is a membranous cell-cell adhesion protein involved in tight-junction formation in epithelial and endothelial cells. Its overexpression in breast tumors has recently been linked with increased risk of metastasis. We sought to identify if JAM-A overexpression was associated with specific subtypes of breast cancer as defined by the expression of human epidermal growth factor receptor-2 (HER2), estrogen receptor (ER) and progesterone receptor. To this end, JAM-A immunohistochemistry was performed in two breast cancer tissue microarrays. In parallel, cross-talk between JAM-A, HER2 and ER was examined in several breast cell lines, using complementary genetic and pharmacological approaches. High JAM-A expression correlated significantly with HER2 protein expression, ER negativity, lower patient age, high-grade breast cancers, and aggressive luminal B, HER2 and basal subtypes of breast cancer. JAM-A and HER2 were co-expressed at high levels in vitro in SKBR3, UACC-812, UACC-893 and MCF7-HER2 cells. Knockdown or functional antagonism of HER2 did not alter JAM-A expression in any cell line tested. Interestingly, however, JAM-A knockdown decreased HER2 and ER-α expression, resulting in reduced levels of phospho-(active) AKT without an effect on the extracellular signal-related kinase phosphorylation. The downstream effects of JAM-A knockdown on HER2 and phospho-AKT were partially reversed upon treatment with the proteasomal inhibitor MG132. We conclude that JAM-A is co-expressed with HER2 and associates with aggressive breast cancer phenotypes. Furthermore, we speculate that JAM-A may regulate HER2 proteasomal degradation and activity, potentially offering a promise as a therapeutic target in HER2-positive breast cancers.

A randomised, split-face comparison of facial hair removal with the alexandrite laser and intense pulsed light system.

INTRODUCTION: Despite the high incidence of polycystic ovary syndrome (PCOS) in women attending for facial hair removal there are few studies looking specifically at this patient group. We carried out a split-face study directly comparing the efficacy of a 3 milliseconds pulse duration alexandrite laser with the Lumina IPL system in 38 women with PCOS. MATERIALS AND METHODS: Each patient underwent six treatments using both systems, with 1, 3 and 6 months follow-up. Hair counts, hair-free intervals and patient satisfaction were recorded for all patients. RESULTS: After six treatments, alexandrite laser treatment resulted in longer median hair-free intervals when compared to IPL (7 weeks vs. 2 weeks; P < 0.001). Decrease in hair counts was significantly larger on the Alexandrite side compared to the IPL side at 1, 3 and 6 months (52%, 43% and 46% vs. 21%, 21% and 27%; P < 0.001). Patient satisfaction scores, using linear analogue scales (LAS), at 1, 3 and 6 months were significantly higher for the alexandrite laser than the IPL (8.7, 7.8 and 7.7 vs. 5.7, 5.1 and 5.1; P < or = 0.002). CONCLUSIONS: The alexandrite laser resulted in significantly longer hair-free intervals, a larger reduction in hair counts and greater patient satisfaction than the IPL and appeared to be more effective in this patient group. It is clear from the results in this study that the GentleLase alexandrite laser is more effective at reducing facial hirsutism in women with PCOS than the Lumina IPL. It is probable that this is due to the specific wavelength, short pulse duration and single pulse delivery of the GentleLase alexandrite laser, resulting in more follicular destruction than the IPL.

Molecular basis of invasion in breast cancer.

Cancer cell invasion involves the breaching of tissue barriers by cancer cells, and the subsequent infiltration of these cells throughout the surrounding tissue. In breast cancer, invasion at the molecular level requires the coordinated efforts of numerous processes within the cancer cell and its surroundings. Accumulation of genetic changes which impair the regulation of cell growth and death is generally accepted to initiate cancer. Loss of cell-adhesion molecules, resulting in a loss in tissue architecture, in parallel with matrix remodelling may also confer a motile or migratory advantage to breast cancer cells. The tumour microenvironment may further influence the behaviour of these cancer cells through expression of cytokines, growth factors, and proteases promoting chemotaxis and invasion. This review will attempt to summarise recent work on these fundamental processes influencing or facilitating breast cancer cell invasion. (Part of a Multi-author Review).

Laser hair removal in women with polycystic ovary syndrome.

UNLABELLED: Polycystic ovary syndrome (PCOS) is one of the most common reasons for women to present seeking removal of facial hair, particularly within the UK National Health Service (NHS). In the NHS, there is geographical variation in the number of laser treatments available to women with PCOS, with some units limiting patients to six treatments whilst others allow unlimited treatments. This study aims to assess the effect of number of treatments on women with PCOS. METHODS: This study prospectively assessed hair counts, hair-free intervals and patient satisfaction in 60 women with PCOS undergoing 3ms pulse duration alexandrite laser treatment. RESULTS: Following six treatments there was a mean 31+/-38% reduction in hair counts (mean+/-SD; P=0.001). Mean hair-free interval (HFI) increased steadily with treatment, from 1.9 weeks after six treatments to 4.3 weeks after 10 treatments (P=0.001). From the postal questionnaire, after an average of 12 treatments, 31% of patients had a HFI longer than 6 weeks compared to only 2.6% after six treatments (P=0.003). Overall, despite the low hair count reductions, 95% of patients were satisfied with treatment. CONCLUSION: In women with PCOS, laser treatment is associated with a poorer than expected reduction in hair counts and HFI following treatment. However, offering more than six treatments does have additional benefits in terms of prolonging HFI and overall patient satisfaction with treatment is very high.

The couch and the cloth: the need for linkage.

Data from the Epidemiologic Catchment Area study were used to compare the demographic characteristics and psychiatric symptomatology of persons classified into four groups based on source of mental health services: clergy only, mental health specialists only, both clergy and mental health specialists, and neither source. Those receiving services from both clergy and mental health specialists were more likely to have major affective and panic disorders than those who sought services from clergy or mental health specialists only or who sought services from neither. Those in the care of mental health specialists were more likely to have substance abuse disorders. Those in the care of clergy only were as likely as those seeing mental health specialists only to have serious mental disorders. The data make clear the need for formal linkages between clergy and mental health professionals.

Quality assurance in DNR (do not resuscitate) decisions--the role of chaplaincy: a case report and a 92 patient group study.

This paper describes 10 indicators of quality assurance for DNR decisions developed by a New England hospital's chaplaincy. It then looks at how these 10 indicators were applied to a specific case and subsequently to the hospital's group of 92 terminal cases. Recommendations were also made for each responsibility group in the hospital.

The DRG era: a major opportunity for increased pastoral care impact or a crisis for survival?

Notes how the Diagnostic Related Group (DRG) system, now being utilized by a growing number of hospitals, may provide chaplains with ways of demonstrating their worth as team members in total health care. Claims that pastoral care ought to be a major clinical service in a hospital and that chaplains therefore need to provide objective evidence of their contribution to the well-being of patients, as do other major clinical areas. Suggests specific ways for chaplains to establish such data, including the use of objective measures of the spiritual conditions of patients. Offers examples of accountability procedures and notes that such meticulous chaplain accountability along with follow-up work with patients could lead to expansions of services and new roles in the chaplaincy fields.

The need and appropriateness of measurement and research in chaplaincy: its criticalness for patient care and chaplain department survival post 1987.

To bring their discipline, Health Care in the Spiritual Dimension, up to late 20th/early 21st century clinical science standards, chaplaincy departments must immediately start to utilize objective instruments for clinical care and for management reporting. This is critical not only for quality of patient care but also for longterm survival of chaplain departments. This paper is a major survey of the best of the numerous, recently developed, spiritual dimension instruments. Also included are examples of how clinical-research findings from a recent hospital chaplaincy study, can be interpreted to assist local chaplaincy department programs and budgets. Such measurement, when properly interpreted, also can play a key role in the future of more adequate training of spiritual health providers by theological professional schools.

Pastoral care departments: more necessary in the DRG era?

Strengthening the spiritual part of a patient can speed recovery to the patient's fullest health capacity. It also creates consumer satisfaction and can give the hospital a significant competitive edge.

Incidence of radiographically evident bone disease, nephrocalcinosis, and nephrolithiasis in various types of renal tubular acidosis.

The syndrome of renal tubular acidosis has been categorized into three physiologic types that have different clinical findings and prognostic and therapeutic implications. We reviewed radiographs of the skeleton and kidneys in 92 patients (56 children and 36 adults) with renal tubular acidosis in order to determine whether the radiologic findings could be related to the type of syndrome. Forty-four patients had Type 1 renal tubular acidosis, 18 had Type 2, and 30 had Type 4. Evidence of skeletal abnormalities was uncommon (17 per cent) and was confined to patients who had the Type 2 disorder or azotemia. The children with Type 2 and skeletal abnormalities had rickets; the adults had osteopenia without pseudofractures. Nephrocalcinosis was evident in approximately one fourth of the group (29 per cent) and was restricted to patients with the Type 1 syndrome. In patients with Type 4, osteopenia was evident in 12 per cent, all of whom were azotemic. Our observations indicate that the radiographic manifestations of renal tubular acidosis are influenced by the physiologic type of renal tubular acidosis.

Renal excretion of pseudoephedrine.

A patient with renal acidosis developed unanticipated toxicity after ordinary doses of pseudoephedrine, prompting us to study renal determinants of its elimination. We presumed that our patient accumulated the drug because of her persistently alkaline urine, which would favor tubular resorption of this weak base (pKa = 9.4). We studied normal adults and children and one adult and one child with renal tubular acidosis. Increasing urine pH increased the serum elimination half-life from 1.9 to 21 hr. While urinary pH remained alkaline, renal excretion of pseudoephedrine and its metabolite, norpseudoephedrine, was directly correlated with the flow rate of urine in each subject. Both urine pH and flow are important determinants of the elimination of pseudoephedrine in man and could be critical determinants of unanticipated toxicity.

Acidosis and growth in nonuremic renal disease.

Our data demonstrate that correction of acidosis is sustained in children with type 1 RTA when alkali therapy is given in doses of 5 to 14 mEq/kg/day. The large doses are required as a result of renal bicarbonate-wasting. Children with type 1 RTA and acidosis who have significant growth impairment experience catch-up growth and attain normal stature for their age when correction of acidosis is sustained. Whether chronic acidosis impairs growth in any clinical condition except type 1 RTA is not settled. Whether sustained correction of acidosis with alkali therapy will allow attainment of normal stature in children with nonuremic diffuse renal disease is not yet determined. With the increasing availability of microchemistry and microgasometry and the new standards for growth based on mean-parent height [40], it can be anticipated that answers to these clinically important questions will be forthcoming.

Attainment and maintenance of normal stature with alkali therapy in infants and children with classic renal tubular acidosis.

Growth was evaluated in a group of 10 infants and children with familial or idiopathic classic renal tubular acidosis in whom alkali therapy was initiated at ages ranging from 8 days to 9.5 yr and administered at dosage schedules documented to sustain correction of acidosis in at least four prolonged observation periods on the Pediatric Clinical Research Ward. When alkali therapy was begun, six patients (four infants and two children) were stunted (height <2.5 SD below mean). Of the four who were not, two infants were too young (<2 wk of age) to have become stunted, and two children had been documented earlier to be nonacidotic. At the start of alkali therapy, the heights of the patients correlated inversely with the maximal possible duration of prior acidosis. WITH SUSTAINED ALKALI THERAPY: (a) each patient attained and maintained normal stature; (b) the mean height of the 10 patients increased from the 1.4+/-4 to the 37.0+/-33 percentile (of a normal age- and sex-matched population); (c) the mean height reached the 69th percentile in the eight patients whose heights could be analyzed according to parental prediction (Tanner technique); (d) the rate of growth increased two- to threefold, and normal heights were attained within 6 mo of initiating alkali therapy in the stunted infants and within 3 yr in the stunted children; (e) the height attained correlated inversely with the maximal possible duration of acidosis (before alkali therapy) only in those patients in whom alkali therapy was started after 6 mo of age, and not in those treated earlier. The amount of alkali required to sustain correction of acidosis increased substantially during the course of treatment in each patient. The maximal alkali requirement ranged from 4.8 to 14.1 meq/kg per day, and in each patient its amount was determined principally by the magnitude of renal bicarbonate wasting.

Impaired renal conservation of sodium and chloride during sustained correction of systemic acidosis in patients with type 1, classic renal tubular acidosis.

In 10 patients with classic renal tubular acidosis in whom correction of acidosis was sustained with orally administered potassium bicarbonate, renal conservation of sodium was evaluated when dietary intake of sodium was restricted to 9--13 meq/day. In five patients, renal conservation of sodium was impaired by at least one criterion of impairment. In the remaining patients, renal conservation of sodium appeared to be relatively well-maintained, but an impairment could not be excluded. In each of six patients studied during induced water diuresis, including two in whom renal conservation of sodium was not unequivocally impaired, the minimal urinary concentrations of sodium were inappropriately high and the urinary excretion rates of sodium were flow-dependent. These results provide direct evidence that an abnormality in renal transport of sodium can occur in classic renal tubular acidosis, and compel a reconsideration of the pathophysiology of disordered renal transport of sodium in this disorder. The results indicate that in at least some patients with classic renal tubular acidosis impaired renal conservation of sodium is not exclusively a reversible consequence of the renal acidification defect. These findings raise the question whether renal transport of sodium is unimpaired in any patients with classic renal tubular acidosis. In the presently studied patients, the impairment in renal conservation of sodium appeared to be in part the consequence of an impaired ability of the vasopressin-responsive segments of the distal nephron to generate and maintain appropriately steep transepithelial sodium concentration gradients.