Incidence of major chromosomal abnormalities in a referred population for suspected chromosomal aberrations: a report of 357 cases

The present report describes the cytogenetic findings in 357 cases referred for suspected chromosomal abnormalities because of abnormal clinical features. Chromosomal anomalies were found in 97 (27.2 %) of the cases studied. A significantly high rate of chromosomal abnormalities was found in a population with clinical abnormalities in comparison to an unselected population (0.48–0.55 %).     

Comparative genotyping of Campylobacter jejuni by amplified fragment length polymorphism,multilocus sequence typing,and short repeat sequencing: strain diversity,host range,and recombination

Three molecular typing methods were used to study the relationships among 184 Campylobacter strains isolated from humans, cattle, and chickens. All strains were genotyped by amplified fragment length polymorphism (AFLP) analysis, multilocus sequence typing (MLST), and sequence analysis of a genomic region with short tandem repeats designated clustered regularly interspaced short palindromic repeats (CRISPRs). MLST and AFLP analysis yielded more than 100 different profiles and patterns, respectively. These multiple-locus typing methods resulted in similar genetic clustering, indicating that both are useful in disclosing genetic relationships between Campylobacter jejuni isolates. Group separation analysis of the AFLP analysis and MLST data revealed an unexpected association between cattle and human strains, suggesting a common source of infection. Analysis of the polymorphic CRISPR region carrying short repeats allowed about two-thirds of the typeable strains to be distinguished, similar to AFLP analysis and MLST. The three methods proved to be equally powerful in identifying strains from outbreaks of human campylobacteriosis. Analysis of the MLST data showed that intra- and interspecies recombination occurs frequently and that the role of recombination in sequence variation is 50 times greater than that of mutation. Examination of strains cultured from cecum swabs revealed that individual chickens harbored multiple Campylobacter strain types and that some genotypes were found in more than one chicken. We conclude that typing of Campylobacter strains is useful for identification of outbreaks but is probably not useful for source tracing and global epidemiology because of carriage of strains of multiple types and an extremely high diversity of strains in animals.     

Tests for detecting degradation of gelatin: comparison of five methods.

Five methods for detecting degradation of gelatin by bacteria were compared. These were liquefaction in nutrient broth, hydrolysis in nutrient agar, hydrolysis of charcoal gelatin strips, degradation of the gelatin on strips of photographic film, and alkalinization of gelatin agar. Degradation of photographic film is a rapid and convenient method but, like hydrolysis of gelatin in broth and in agar, may fail to detect weakly positive strains of bacteria. Alkalinization of gelatin in an agar medium is a convenient and sensitive method to detect degradation of gelatin, particularly by Pseudomonas fluorescens, but this method may not be applicable to some species.     

Impaired hepatocyte survival and liver regeneration in Atm-deficient mice

Atm is a stress-induced DNA damage checkpoint protein kinase with multiple roles in cell-cycle progression. Recent evidence indicates that Atm also plays a role in stem cell maintenance and self-renewal. It is not known whether Atm has a role during tissue regeneration. Using liver regeneration as a model system, we examined the role of Atm in this process. Here, we show that the expression levels of Atm protein were gradually increased during liver regeneration and this was correlated with the onset of DNA replication. The induction of Stat3 and JNK signaling, which are essential processes in normal regeneration response, was attenuated during the early phases of liver regeneration in Atm-deficient mice. P53 was transiently phosphorylated at serine 23 during liver regeneration in an Atm-dependent manner. In addition, we found that cyclin A induction was delayed and p21 was over-expressed, both of these processes were correlated with reduced and delayed DNA replication in Atm(-/-) mice during liver regeneration. Finally, we show that increased apoptosis was observed in Atm(-/-) mice in response to partial hepatectomy, indicating that Atm is required for the survival of hepatocytes. Collectively, these data indicate that liver regeneration is impaired in Atm-deficient mice. Given that liver is the first line of defense against environmental toxins, the elucidation of the function of Atm and Atm-mediated signaling pathways in liver metabolism and in response to environmental toxins is of fundamental interest.     

Genotypic analysis of sequential genital herpes simplex virus type 1 (HSV-1) isolates of patients with recurrent HSV-1 associated genital herpes

Clinical recurrences of Herpes simplex virus type 1 (HSV-1)-associated genital herpes are thought to be caused by reactivation of latent endogenous HSV-1. However, the possibility of reinfection with exogenous HSV-1 cannot be excluded. This study aimed to determine the incidence of genital HSV-1 superinfection in patients by investigating the genotype of sequential HSV-1 isolates obtained from the same anatomical site of patients with clinical recurrences of genital HSV-1 recurrent genital herpes. Sequential genital HSV-1 isolates were genotyped by PCR amplification of the hypervariable regions located within the HSV-1 genes US1 and US12. Whereas the sequential HSV-1 isolates in 11 of the 13 patients studied had the same genotypes, the sequential isolates of 2 patients showed a different genotype. The data suggest that HSV-1-induced recurrent genital herpes can be associated with genital reinfection with an exogenous HSV-1 strain.     

Users and non-users of doctors — implications for self-care

Sixty patients who visited their general practitioner were matched with 60 patients registered with the same doctor, who were of the same sex and in the same ten-year age group, and who had not visited the doctor for at least one year, but had recently experienced symptoms similar to those presented by the attending patients.

Comparison of the 60 pairs revealed the following differences, all substantial although not all statistically significant. The patients who visited the doctor perceived themselves as less healthy, fewer had attempted self-treatment, more reported serious personal problems, and fewer reported obstacles to visiting the doctor.

Differences between the pairs were negligible for total number of current ailments, effectiveness of self-treatment, if used, optimism about the healing powers of doctors, and fear of troubling their doctor with trivia.

     

Vascular studies with histamine in vitro

In vitro studies to analyse the pharmacology of histamine-induced dilatation of resistance vessels in rat hindquarters have been made. Histamine caused dose-dependent dilatation of resistance vessels over the concentration range 10^–9 to 10^–6 mol. Responses to histamine were antagonized by cimetidine but not by mepyramine. Dimaprit also caused vasodilatation. Responses to dimaprit were inhibited by cimetidine 10^–6 to 10^–5 M. A pA₂ of 6.43 (6.11–6.75, 95% confidence limits) was calculated for cimetidine in the resistance vessels of the hindquarters.     

Pathologic explanation for postoperative obstipation in Hirschsprung's disease revealed with monoclonal antibody staining

Until now, no pathologic explanation could be found for the postoperative obstipation occurring in some patients with intestinal aganglionosis. Twenty-two of 108 infants treated for intestinal aganglionosis suffered from postoperative obstipation. Resected material from these 22 patients and from 17 control subjects was investigated with monoclonal anti-neurofilament antibody staining. An abnormal staining pattern was revealed in 18 of the constipated patients. Consequently, this new immunohistochemical staining technic has revealed a hitherto unsuspected cause for postoperative obstipation in aganglionosis. The monoclonal antibody may provide early warning of such postoperative constipation.     

Hapten-induced colitis associated with maintained Th1 and inflammatory responses in IFN-gamma receptor-deficient mice

IFN-gamma is a potent pro-inflammatory cytokine thought to be involved in the pathogenesis of Crohn's disease. To further define the role of IFN-gamma in intestinal inflammation, we studied the effects of intra-colonic 2,4,6-trinitrobenzene sulfonic acid (TNBS) instillation in mice with a functionally inactivated IFN-gamma receptor 1 (IFN-gammaR1(- / -)). Our results indicate that IFN-gamma is not necessary for the induction of hapten-induced colitis: after TNBS administration both wild-type and IFN-gammaR1(- / -) mice lost body weight, and the histological features of TNBS-induced colitis were comparable. Colons of IFN-gammaR1(- / -) mice contained a greater number of cells, represented by macrophages and CD4(+) T cells; caudal lymph node cells produced more IFN-gamma and TNF-alpha upon stimulation in vitro. Moreover, IL-18 and IL-12 p40 RNA levels were comparably up-regulated after TNBS treatment in IFN-gammaR1(- / -) wild-type mice. These findings demonstrate that IFN-gamma is dispensable for the development of TNBS-induced colitis. Importantly, the production of Th1 cytokines (e. g. IFN-gamma and TNF-alpha) by caudal lymph node T lymphocytes was enhanced rather than decreased in IFNgammaR1(- / -) mice with no evidence for default Th2 development.     

An investigation of the disclosure process and support needs of BRCA1 and BRCA2 carriers

Disclosure of the results of a positive genetic mutation to offspring can be challenging. The purpose of this study was to investigate the content and process of disclosure from BRCA1/2 carriers to their offspring. A semi-structured questionnaire focused on the disclosure processes between parent and offspring. Thirty-one/40 mothers with BRCA1/2 mutations completed the cross-sectional survey. Sixteen carriers (51.6%) chose to disclose their results to all of their children, thirteen carriers (41.9%) chose not to disclose their results, and two carriers (6.5%) chose to disclose to some of their children. The age of a child appeared to be the most significant contributing factor in the decision to disclose. The mean age of the offspring who learned of the positive test result was 24.3 years with most carriers advocating the ideal age range for disclosure from 19 to 25 years. There was a discrepancy between actual and potential disclosure topics between those who had disclosed and those who had not disclosed at the time of the survey. Women who disclosed their result tended to do so alone, within a week of learning their own results, equally to male and female offspring and expressed that the relationships between themselves and their children had strengthened since revealing the presence of a genetic mutation in the family. Women who had not disclosed the results of their genetic test to offspring were significantly more interested in receiving additional individual counseling, educational videos, and email newsletters that focus on disclosure of this complex and life altering information compared to those who had already disclosed. Disclosure of BRCA1/2 results is determined primarily by age of offspring, is usually done by women alone, relatively soon after receiving results and appears to enhance the relationships between mothers and offspring. Both disclosed and non-disclosed carriers demonstrated significant interest in a variety of interventions to support the disclosure process.