A small molecular weight factor in aqueous humor acts on C1q to prevent antibody-dependent complement activation

OBJECTIVE: To review the current literature on genes known to affect fertility in the human and mouse. DESIGN: A literature review was performed and key articles were chosen for focus in the areas of genes with effects only on spermatogenesis and oogenesis, with an emphasis on Y-chromosome-encoded gene families and spermatogenesis. In addition, studies describing genes deleted in transgenic mice were incorporated. RESULT(S): Several gene families on the Y chromosome are implicated in spermatogenic failure, but the link between the genetic lesion and the resulting defect is unclear. Many mouse genes involved in repair and DNA damage monitoring have specific effects on gametogenesis in and around meiosis. CONCLUSION(S): Many genes are involved only in gametogenesis, and some of these are beginning to be understood in terms of their functions. An even larger number of genes is required for gametogenesis, and other functions and mouse models give insights important for human disease.     

Quantification of white matter and gray matter volumes from T1 parametric images using fuzzy classifiers

Implementation of clinical practice guidelines in a large setting is a complex process. This article describes the many issues encountered in trying to implement Agency for Health Care Policy and Research acute pain and cancer pain guidelines in an academic medical center. Issues addressed include the membership of the task forces involved, incorporation of the guidelines into the institution-specific standards of care, selection and implementation of self-reporting tools for assessment of pain throughout the institution, issues involved in standardizing documentation of pain throughout the institution, measurement of the current status of pain control and integration into the existing quality assessment and improvement program, various analgesic interventions addressed throughout the hospital, educational strategies used and planned, and how multidisciplinary involvement was obtained.     

Phenotype, function, and in vivo migration and survival of allogeneic dendritic cell progenitors genetically engineered to express TGF-beta

BACKGROUND: Administration of donor bone marrow (BM)-derived dendritic cell (DC) progenitors (DCp) that are major histocompatibility complex (MHC) class II+ but costimulatory molecule (CD40, CD80, CD86)-deficient can prolong mouse heart allograft survival This is associated with microchimerism and inhibition of antidonor cytotoxic T lymphocyte (CTL) activity. Genetic modification of these donor antigen-presenting cells to express an immunosuppressive molecule(s) may enhance their in vivo survival and potential tolerogenicity. METHODS: The surface phenotype of B10(H-2b) DCp before and after gene transfer using replication-deficient adenoviral (Ad) vectors was determined by monoclonal antibody (mAb) staining and flow cytometry. Transforming growth factor-beta (TGF-beta) production was quantitated by enzyme-linked immunosorbent assay. Allostimulatory activity of the gene-transduced DCp was ascertained by mixed leukocyte reaction (MLR) and CTL induction. To assess their in vivo migratory activity and survival, the transduced cells were injected subcutaneously into one hind footpad of C3H (H-2k) mice. Tissues (draining popliteal lymph nodes [LN], spleens, and thymi) were removed 1, 2, 7, and 14 days later and stained for donor MHC class II using anti-LA(b) mAb in an immunohistochemical procedure. The mean number of IAb+ cells per unit area was determined. RESULTS: Transduction with a control Ad vector (Ad-LacZ) at 50 multiplicity of infection slightly increased CD40 and CD86 expression and up-regulated the poor allostimulatory activity of the DCp assessed by MLR and CTL responses. These effects on function were negated in Ad-TGF-beta1-transduced cells. After their injection into mouse footpads, the gene-transduced IAb+ cells were observed in maximal numbers in the popliteal LN at day 1 and in marginal zones and T-dependent areas of spleens (peak at day 7) but were rare in thymi. Transduction with Ad-LacZ reduced the numbers of IAb+ cells identified in both LN and spleens at all time points postinjection, suggesting that the vector alone affected DC life span in allogeneic recipients. TGF-beta1 transgene expression not only fully prevented the reduction in DC induced by Ad transduction alone, but also increased numbers and prolonged the survival of donor cells in the spleen, as shown by a two-to fivefold increase in IAb+ cells at days 2-14 compared with control (Ad-LacZ-transduced) DC. CONCLUSION: BM-derived DCp can be transduced efficiently to express TGF-beta1 using an Ad vector. They exhibit very poor allostimulatory activity and similar migration characteristics in vivo to unmodified DCp. Survival of TGF-beta gene-transduced DC, however, is enhanced significantly compared with unmodified and (especially) control Ad-LacZ gene-transduced DC. Genetic engineering of donor DC to express the immunosuppressive molecule TGF-beta promotes their survival in allogeneic hosts and may potentiate their previously reported tolerogenicity.     

Development of a green fluorescent protein reporter for a yeast genotoxicity biosensor

A reporter system, constructed for a laboratory screen for new genes involved in DNA repair in the brewer's yeast Saccharomyces cerevisiae, has been developed for use in a genotoxicity biosensor. The strain produces green fluorescent protein (yEGFP) when DNA damage has occurred. yEGFP is codon optimised for yeasts. The reporter does not respond to chemicals which delay mitosis, and responds appropriately to the genetic regulation of DNA repair. Data is presented which demonstrate strain improvements appropriate to biosensor technology: improved signal to noise ratio, ease of data collection and uncomplicated material handling.     

Sports medicine and the Americans with Disabilities Act

Consequently an infarct in the territory of the right middle cerebral artery, a 77-year old man had a complete left sensory motor hemiplegia, with left neglect. For several weeks, he described the existence of one and more supernumerary phantom limbs. The patient's adamant and delusional conviction of their reality caused him considerable distress. Without being anosognosic he was not completely aware of his disorder, and had slight difficulties in judging what was plausible. The mechanisms underlying this delusion concerning specific parts of the body probably involve multifactorial disorders: first, a sensory deafferentation source of a distorsion of the perceived body schema; second, a resulting discrepancy between the perception of the body schema and its innate representation; third abnormalities of self-awareness and of self-judgement, leading the patient to argue forcellully in favor of incongruous rationalizations.     

The infrarenal aortic diameter in relation to age: only part of the population in older age groups shows an increase

The aim of the present investigation was to study the relationship between ascorbic acid status during the third trimester of pregnancy and levels of this vitamin in transition milk (days 13-14 of lactation) and mature milk (day 40 of lactation). To this end, the pregnancies and lactation periods of fifty-seven healthy women between 18 and 35 years of age (27 (SD 3.7) years) were monitored. Vitamin intake during the third trimester was determined by recording the consumption of foods over 5 d, and by registering the quantities provided by dietary supplements. Ascorbic acid levels in maternal serum during this stage of pregnancy, and in transition and mature milk samples, were determined by spectrophotometry. Those subjects with ascorbic acid intakes below that recommended (80 mg/d) (group L) showed lower consumption of fruit and vegetables than did those with greater intakes (group H). The consumption of ascorbic acid supplements was very low, and was only seen in three group H subjects. The difference in ascorbic acid intake was reflected at serum level. Group L subjects showed significantly lower serum values than did group H subjects (30.1 (SD 36.3) mumol/l compared with 101.1 (SD 168.1) mumol/l). Vitamin intake also influenced the composition of transition milk. Group L subjects showed significantly lower levels of ascorbic acid in milk than did group H subjects (255.5 (SD 220.3) mumol/l compared with 437.8 (SD 288.4) mumol/l). The results of the present study reveal the need to increase the consumption of fruits and vegetables during pregnancy and to monitor maternal ascorbic acid intake and vitamin C status.     

Salvage of infected orthopedic devices

To determine whether the autosomal dominant fibroblast growth factor receptor 3 (FGFR3) Pro250Arg mutation causes anterior plagiocephaly, patients with either apparently sporadic unicoronal synostosis (N = 37) or other forms of anterior plagiocephaly (N = 10) were studied for this mutation. Of 37 patients with unicoronal synostosis, 4 tested positive for the Pro250Arg mutation in FGFR3, and 33 were negative for this mutation. In three mutation positive patients with full parental studies, a parent with an extremely mild phenotype was found to carry the same mutation. None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation. Because it is impossible to predict the FGFR3 Pro250Arg mutation status based on clinical examination alone, all patients with unicoronal synostosis should be tested for it. To assess their recurrence risk, all parents of mutation positive patients should be tested regardless of their clinical findings, because the phenotype can be extremely variable and without craniosynostosis.     

Predischarge screening of very low birthweight infants by click evoked otoacoustic emissions

Idiopathic edema patients abusing diuretics are occasionally becoming dependent to such a degree on increasing doses of diuretics that their withdrawal results in severe cardiorespiratory failure, occasionally even pulmonary edema. Two such patients are described and 1 is investigated in depth as to the mechanism of the diuretic abuse-induced excessive tubular avidity for sodium. An extreme diuretic-induced secondary hyperaldosteronism and atrial natriuretic factor suppression, although tapering off when diuretics are stopped, results in a continuous tubular sodium hyper-reabsorption. Since the most affected patient was deprived of the benefits of converting enzyme inhibitors because of their side effects, the only way to partially overcome this condition was a generous combination of several diuretics acting at several segments of the nephron. This contrasted with a similar patient who was relatively well controlled by a converting enzyme inhibitor combined with lower dose diuretics. Diuretic abuse-induced secondary hyperaldosteronism and diuretic resistance are apparently best prevented by converting enzyme inhibitors. When nonpharmacological preventive measures fail, converting enzyme inhibitors are preferable to diuretics as the first-choice treatment of idiopathic edema patients.     

Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair

T helper 1 responses are typically proinflammatory, while Th2 responses have been considered regulatory. Interestingly, Th2 responses characterize a number of pulmonary diseases, many of which terminate in tissue remodeling and fibrosis. We developed a mouse model using Schistosoma mansoni eggs and cytokine-deficient mice to induce highly polarized Th1- or Th2-type inflammation in the lung. In this study, we examined the pathology and cytokine profiles in Th1- and Th2-polarized environments and used oligonucleotide microarray analysis to decipher the genes responsible for these effects. We further elaborated on the results using IL-10- and IL-13-deficient mice because these cytokines are believed to be the central regulators of Th2-associated pathology. We found that the Th1-polarized mice developed small granulomas with less fibrosis while expressing genes characteristic of tissue damage. Th2-polarized mice, in contrast, formed large granulomas with massive collagen deposition and up-regulated genes associated with wound healing, specifically, arginase, collagens, matrix metalloproteinases (MMPs), and tissue inhibitors of MMP. In addition, several members of the chitinase-like family were up-regulated in the lung following egg challenge. We also developed a method of defining the net collagen deposition using the expression profiles of several collagen, MMP, and tissue inhibitors of MMP genes. We found that Th1-polarized mice did not elaborate collagens or MMPs and therefore did not have a significant capacity for repair in this model. Thus, Th1-mediated inflammation is characterized by tissue damage, while Th2 directs wound healing and fibrosis.     

Results of radical prostatectomy in men with clinically localized prostate cancer

OBJECTIVE: To assess the results of radical prostatectomy in men with early prostate cancer. DESIGN: Retrospective, nonrandomized, multi-institutional pooled analysis. SETTING: Eight university medical centers in the United States and Europe. PATIENTS: A total of 2758 men with stage Tl and T2 prostatic cancer. MAIN OUTCOME MEASURES: Disease-specific and metastasis-free survival rates. RESULTS: Tumor grade was the most important preoperative factor in determining outcome. Disease-specific survival 10 years following surgery and associated 95% confidence intervals were 94% (range, 87%-98%), 80% (range, 74%-85%), and 77% (range, 65%-86%) for those men with grade 1, 2, and 3 tumors, respectively. Metastasis-free survival at 10 years was 87% (range, 78%-92%), 68% (range, 62%-73%), and 52% (range, 38%-64%) for patients with grade 1, 2, and 3 cancers, respectively. CONCLUSIONS: Radical prostatectomy leads to high 10-year disease-specific survival rates in men with all tumor grades. However, caution is needed in comparing these results with similar studies of alternative treatment strategies, such as watchful waiting, due to the inherent potential biases in uncontrolled trials. Nevertheless, these results offer the best currently available estimates of 10-year outcome of radical prostatectomy in men with clinically localized prostate cancer and may be useful in counseling patients with early malignancy.