Large-scale comparative genomics meta-analysis of Campylobacter jejuni isolates reveals low level of genome plasticity

We have used comparative genomic hybridization (CGH) on a full-genome Campylobacter jejuni microarray to examine genome-wide gene conservation patterns among 51 strains isolated from food and clinical sources. These data have been integrated with data from three previous C. jejuni CGH studies to perform a meta-analysis that included 97 strains from the four separate data sets. Although many genes were found to be divergent across multiple strains (n = 350), many genes (n = 249) were uniquely variable in single strains. Thus, the strains in each data set comprise strains with a unique genetic diversity not found in the strains in the other data sets. Despite the large increase in the collective number of variable C. jejuni genes (n = 599) found in the meta-analysis data set, nearly half of these (n = 276) mapped to previously defined variable loci, and it therefore appears that large regions of the C. jejuni genome are genetically stable. A detailed analysis of the microarray data revealed that divergent genes could be differentiated on the basis of the amplitudes of their differential microarray signals. Of 599 variable genes, 122 could be classified as highly divergent on the basis of CGH data. Nearly all highly divergent genes (117 of 122) had divergent neighbors and showed high levels of intraspecies variability. The approach outlined here has enabled us to distinguish global trends of gene conservation in C. jejuni and has enabled us to define this group of genes as a robust set of variable markers that can become the cornerstone of a new generation of genotyping methods that use genome-wide C. jejuni gene variability data.     

The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors

The Ras homolog enriched in striatum, Rhes, is the product of a thyroid hormone-regulated gene during brain development. Rhes and the dexamethasone-induced Dexras1 define a novel distinct subfamily of proteins within the Ras family, characterized by an extended variable domain in the carboxyl terminal region. We have carried this study because there is a complete lack of knowledge on Rhes signaling. We show that in PC12 cells, Rhes is targeted to the plasma membrane by farnesylation. We demonstrate that about 30% of the native Rhes protein is bound to GTP and this proportion is unaltered by typical Ras family nucleotide exchange factors. However, Rhes is not transforming in murine fibroblasts. We have also examined the role of Rhes in cell signaling. Rhes does not stimulate the ERK pathway. By contrast, it binds to and activates PI3K. On the other hand, we demonstrate that Rhes impairs the activation of the cAMP/PKA pathway by thyroid-stimulating hormone, and by an activated beta2 adrenergic receptor by a mechanism that suggests uncoupling of the receptor to its cognate heterotrimeric complex. Overall, our results provide the initial insights into the role in signal transduction of this novel Ras family member.     

Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome

OBJECTIVE: To determine the prevalence and the effect of premature luteinization in GnRH antagonist IVF-ET cycles. DESIGN: Prospective observational study. SETTING: In vitro fertilization-embryo transfer (IVF-ET) program at the Instituto Valenciano de Infertilidad. PATIENT(S): Eighty-one infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for IVF-ET. INTERVENTION(S): Gonadotropin-releasing hormone (GnRH) antagonist was administered from stimulation day 6. Serum P, E(2), and LH were determined on the day of hCG administration. MAIN OUTCOME MEASURE(S): Cycles were grouped according to serum P level on the day of hCG administration (<1.2 ng/mL or > or =1.2 ng/mL). Clinical pregnancy and implantation rates were determined. RESULT(S): The incidence of premature luteinization was 38.3%. Total recombinant FSH dose and stimulation days differed significantly between the groups. Pregnancy rate (25.8% vs. 54.0%) and implantation rate (13.8% vs. 32.0%) were significantly lower in the premature luteinization group. CONCLUSION(S): Premature luteinization during GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower pregnancy and implantation rates. Progesterone elevations are not related to serum LH levels and may reflect the mature granulosa cell response to high FSH exposure.     

Gynecomastia in HIV-infected patients receiving antiretroviral therapy

Thirty-four HIV-positive men with gynecomastia were seen in an HIV outclinic during a 20-month period (incidence of 2.4 cases/100 patients receiving HAART per year). It developed mainly in subjects having good immunologic and virologic status, after an average of 3 years of HAART. No hormone abnormalities were found, or association with specific drugs. Although initially unilateral, more than half of cases progressed to bilateral gynecomastia. Spontaneous resolution occurred in most subjects with 12 months without modifying therapy.     

Cardiopulmonary transplantation: experience of a lung transplant group

Cardiopulmonary transplantation (CPT) is indicated for patients eligible for heart transplantation (HT) or lung transplantation (LT) who have severe concomitant lung or heart disease. Only 2 groups perform CPT in Spain. We report our experience with 18 CPTs representing 8.2% and 5% compared with LT (220) and HT (362), respectively, from February 13, 1990 to October 15, 2002. The mean time on a waiting list was 138 days. The current number of surviving patients is 7 (39%), with a mean follow-up of 602 days (range, 3 to 4627 days). They all remain asymptomatic with normal respiratory function in 4 patients. No cardiac graft rejection has been detected. Two patients experienced sustained gastroparesis during the first year with spontaneous resolution. Death occurred within the first 3 months in 9 patients. These outcomes contrast with the early mortality associated with LT and HT in our series, namely 10.6% and 11%, respectively. The different causes of death were as follows: sepsis and multiorgan failure in 5 patients, hemorrhagic shock in 3 patients, and suture dehiscence and fungal aortic perforation in 1 patient. Late mortalities were recorded in 2 cases. Overall patient survival in our series is lower than that reported by the International Registry (IR), with an early mortality rate of 50% (30% IR). Nevertheless, our survival rate at 10 years after transplantation is 30% (26% IR). We conclude that CPT should be considered despite the greater early morbidity and mortality.     

Asystolias in the acute phase of brain stroke. Report of a case

Brain areas involved in heart autonomic control are not well characterized. Insulae have been proposed as control centers. A lesion in these areas may induce a cardiac autonomic dysfunction (arrhythmias, atrioventricular conduction abnormalities). Asystolia has not been previously reported. A 65-year-old man suffered an acute ischemia of the right middle cerebral artery (MCA) territory. NIHSS score was 19 points. Brain CT scan was normal. Transcranial Doppler (TCD) showed occlusion of the right MCA. Fibrinolysis was initiated 135 minutes after stroke onset with TCD monitoring. Twenty minutes later he suffered cardiac arrest with asystolia trace in the ECG monitor. Fibrinolysis was stopped during resuscitation. Four minutes later, he recovered with the same NIHSS score. Aggressive resuscitation maneuvers were not necessary. A repeated brain CT scan showed infarct signs in the whole MCA territory and a new TCD did not show any change. Serial blood analyses including cardiac nzymes were normal. The patient experienced four brief cardiac arrests in the next nine hours, so a temporary cardiac pacemaker was placed for four days. He was treated with aspirin and was discharged 14 days after admission. He has not experienced recurrences during a 6-month follow-up. We could not diagnose the etiology of the cardiac arrests. All the episodes occurred in the acute stroke stage and arrhythmia, atrioventricular block, myocardial ischemia or structural lesions were not found in the cardiac study. We propose that ischemia in the right insula induced sudden and transitory interruptions of the sympathetic cardiac tone.     

Opsoclonus: an early sign of neonatal herpes encephalitis

Preferential involvement of certain central nervous systems areas by specific viruses provides a valuable guide to the selection of antiviral agents. We report a neonate that developed opsoclonus 7 days prior to the diagnosis of herpes simplex type 2 cerebellitis. The course of the opsoclonus paralleled the clinical course and radiologic evolution of the infection. The purpose of this report is to describe opsoclonus as a possible early sign of herpes simplex type 2 central nervous system infection.     

Immunohistochemical markers of cell proliferation in laryngeal carcinoma

Although several clinicopathological factors may contribute to the prognosis of laryngeal carcinoma, these factors are still uncertain because the carcinogenesis process and malignant behavior are not well known. Immunohistochemical methods using two important markers, PCNA and Ki67 antigen, were used to assess proliferative activity in malignant laryngeal lesions. We studied the correlation between expression of these markers and clinical factors in 72 patients with carcinoma of the larynx: age, sex, occupation, smoking, alcohol consumption, marital status, etc. We also analyzed other known biological and histopathological prognostic factors (tumor stage, histological grade, lymph node metastases, and local invasion). PCNA and Ki-67 expression differed significantly in relation to histological grade and lymph node involvement. No associations were seen between the expression of PCNA and Ki-67 antigens and other study parameters.     

Eating in larger groups increases food consumption

OBJECTIVE: To determine whether children's food consumption is increased by the size of the group of children in which they are eating. DESIGN: Crossover study. SETTING: University based preschool. PARTICIPANTS: 54 children, aged 2.5-6.5 years. INTERVENTIONS: Each child ate a standardised snack in a group of three children, and in a group of nine children. MAIN OUTCOME MEASURES: Amount each individual child consumed, in grams. RESULTS: Amount eaten and snack duration were correlated (r = 0.71). The association between group size and amount eaten differed in the short (<11.4 min) versus the long (> or =11.4 min) snacks (p = 0.02 for the interaction between group size and snack duration). During short snacks, there was no effect of group size on amount eaten (16.7 (SD 11) g eaten in small groups vs 15.1 (6.6) g eaten in large groups, p = 0.42). During long snacks, large group size increased the amount eaten (34.5 (16) vs 26.5 (13.8), p = 0.02). The group size effect was partially explained by a shorter latency to begin eating, a faster eating rate and reduced social interaction in larger groups. CONCLUSIONS: Children consumed 30% more food when eating in a group of nine children than when eating in a group of three children during longer snacks. Social facilitation of food consumption operates in preschool-aged children. The group size effect merits consideration in creating eating behaviour interventions.