Prenatal exposure to tobacco smoke sex dependently influences methylation and mRNA levels of the Igf axis in lungs of mouse offspring.

Prenatal smoke exposure is a risk factor for abnormal lung development and increased sex-dependent susceptibility for asthma and chronic obstructive pulmonary disease (COPD). Birth cohort studies show genome-wide DNA methylation changes in children from smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. The insulin-like growth factor (IGF) system plays an important role in lung development. We hypothesized that prenatal exposure to smoke induces lasting changes in promoter methylation patterns of Igf1 and Igf1r, thus influencing transcriptional activity and contributing to abnormal lung development. We measured and compared mRNA levels along with promoter methylation of Igf1 and Igf1r and their protein concentrations in lung tissue of 30-day-old mice that had been prenatally exposed to cigarette smoke (PSE) or filtered air (control). Body weight at 30 days after birth was measured as global indicator of normal development. Female PSE mice showed lower mRNA levels of Igf1 and its receptor (Igf1: P = 0.05; Igf1r: P = 0.03). Furthermore, CpG-site-specific methylation changes were detected in Igf1r in a sex-dependent manner and the body weight of female offspring was reduced after prenatal exposure to smoke, while protein concentrations were unaffected. Prenatal exposure to smoke induces a CpG-site-specific loss of Igf1r promoter methylation, which can be associated with body weight. These findings highlight the sex-dependent and potentially detrimental effects of in utero smoke exposure on DNA methylation and Igf1 and Igf1r mRNA levels. The observations support a role for Igf1 and Igf1r in abnormal development.

Study of density of interstitial cells of cajal in the terminal intestine of rats with anorectal malformation.

INTRODUCTION: Intestinal constipation is one of the most commonly occurring complaints in the postoperative period after correction of anorectal malformation (ARM). An abnormal density of interstitial cells of Cajal (ICC) is one potential cause. The objective of this study was to analyze the density of ICC in the terminal intestine of fetuses of rats with anorectal anomaly induced by ethylenethiourea (ETU). MATERIAL AND METHODS: The fetuses were distributed into three groups: Group A--normal fetuses obtained from pregnant female rats that did not receive ETU; Group B--fetuses with no ARM, obtained from pregnant rats that received ETU, and Group C--fetuses with ARM, obtained from pregnant rats that received ETU. ETU was administered on the 11th day of pregnancy at a dose of 125 mg/kg. The fetuses were extracted by means of laparotomy on the 21st day of pregnancy. The terminal intestine of the fetuses was removed and analyzed by immunohistochemistry to evaluate ICC. RESULTS: Statistically significant differences were found between groups A, B and C regarding the density of ICC. Group A presented with the highest density, followed by groups B and C. CONCLUSION: There is a lower density of ICC in the terminal intestine of rats with ARM.

Immunizing efficacy of a Kenyan strain of Schistosoma mansoni in rhesus monkeys (Macaca mulatta).

The efficacy as an immunizing agent of the Kenyan strain of Schistosoma mansoni against challenge infection in rhesus monkeys was demonstrated. An initial exposure of 200 cercariae immunized monkeys against a challenge dose of 2,000 cercariae administered 16 weeks later. The penetration rate in rhesus monkeys was 99%, the same as in baboons. The prolongation of the time for immunity to develop in baboons, compared to rhesus monkeys, shown with this strain of S. mansoni is therefore not due to a reduced potential for immunization by this strain in the rhesus monkey.

Schistosoma mansoni in baboons. III. The course and characteristics of infection, with additional observations on immunity.

Parasitological, clinical, and histopathological observations on 54 baboons infected with Schistosoma mansoni are presented. The baboon and S. mansoni constitute a compatible host-parasite system, evidence by the infectivity of cercariae (98% penetration, 42% adult worm recovery), and the long, fertile life of the worms. Baboons tolerated the infection well, with clinical illness a rarity in moderately infected baboons. Pathological findings were generally unremarkable. An acute "toxemic" phase occurred 66 days or less following a large cercarial exposure in three baboons. Worm burdens were not significantly reduced during the course of prolonged infection, but prolonged infections resulted in decreased oviposition by the worms and in an anterior shift in egg deposition from the colon to the small intestine. Concomitant immunity was also a feature of baboon infections. Decreased oviposition and the anterior shift are probably manifestations of a second phase of immunity, distinct from concomitant immunity. The baboon is similar to man and the grivet monkey in that in all three species immunity is slow to develop.

Simultaneous laparoscopic pyloroplasty and ileocecal resection in Crohn's disease.

BACKGROUND: The initial manifestation of Crohn's disease is often located within the terminal ileum. Other portions of the G.I. tract may be affected, however, as the disease involves the entire organ system. The disease often progresses chronically in flares and remissions and involves all layers of the intestinal wall, leading to strictures, stenosis and fistulas. These complications should only be treated surgically when clinically relevant in order to prevent acute exacerbations. METHODS: Laparoscopic surgery offers one the possibility to minimize surgical trauma with its very small incisions and proper dissection through the correct anatomical layers with 10-fold optic magnification. RESULTS: Multifocal procedures can be carried out in the same operation. We present the case of a 26-year-old female with terminal ileum stenosis and gastric outlet obstruction, who underwent simultaneous laparoscopic pyloroplasty and ileocecal resection. DISCUSSION: Providing the surgeon possesses the necessary expertise, complex laparoscopic simultaneous procedures.

Effectiveness of live or killed plague vaccines in man.

While the safety of the available live plague vaccine EV 76 (Paris) continues to be the subject of further study, the USP formol-killed, virulent Pasteurella pestis (Yersinia pestis) suspension capable of protecting 60% of non-human primates, particularly Hanuman langurs (Presbytis entellus), warrants further clinical tests and field trials. Inoculated in a dosage of 2x10(9) killed plague bacilli (1 ml), followed by a booster of 400 million organisms (0.2 ml) in 1-3 months, this vaccine stimulates the appearance of passive mouse-protection antibodies (below an index of 10) and passive haemagglutinins in 60%-65% of human subjects. Recent experiences in Viet-Nam demonstrate that personnel vaccinated with the USP vaccine, although frequently exposed, enjoy almost complete freedom from the disease. One of the 4 known and confirmed cases of bubonic plague in North Americans occurred in an unvaccinated individual. Among individuals inoculated with the USP vaccine, 2 confirmed cases of pneumonic plague and 1 case of asymptomatic pharyngeal plague have been recorded. The incidence of plague in the Republic of Viet-Nam during the past 3 years is estimated at 13 263 cases in a population in part vaccinated with a live plague which exhibited inadequate immunogenic efficacy in experimental tests.

An evaluation of Pasteurella pestis fraction-1-specific antibody for the confirmation of plague infections.

Owing to the relatively long duration of specific serum plague antibodies in the host, the serological diagnosis of plague has substantial advantages over the conventional method of isolation of the causative agent. For the performance of both the complement-fixation (CF) and passive haemagglutination (HA) tests, the use of highly purified, specific Fraction 1 antigen is essential, and its preparation is discussed in this paper. Although both tests measure the same antibodies, the passive HA test is the more sensitive and constitutes the most effective means of detecting recovery from plague infection in nature. The CF test is nevertheless invaluable for such purposes as determining the antibody content of sera from immunized or infected hosts, indicating the amount of Fraction 1 developed by strains of Pasteurella pestis in cultures and therefore present in a vaccine, or detecting and estimating the amount of Fraction 1 antigen in extracts prepared from infected animal tissues and therefore for the field diagnosis of wild rodent plague after contamination or decomposition of rodents' carcasses.

Lymphogranuloma venereum. II. Characterization of some recently isolated strains.

Five Bedsonia (Chlamydia) isolates from lymphogranuloma venereum (LGV) patients were tested for inclusion type, sulfonamide sensitivity, and mouse virulence. Two matched the classical description of LGV agents. Two were not virulent for mice by the intracerebral route, therefore fitting the description for trachoma-inclusion conjunctivitis agents. One was highly virulent for mice and sulfonamide-resistant, and produced inclusions that did not stain with iodine, all characteristics generally associated with avian bedsoniae. A sixth isolate could not be adequately tested due to poor infective yields. Because of this variety of properties within the Bedsonia group, the term LGV might more appropriately be reserved for clinical disease rather than to describe a particular bedsonial agent.

Plaque formation by Chlamydia in L cells.

Chlamydiae were found capable of producing plaques in several cell lines. Mouse fibroblast cells, L-929, proved the most sensitive to infection and yielded plaques of the highest clarity. Assay of chlamydial infectivity by plaque titration was at least as sensitive as egg ld(50) determination. Among chlamydial isolates of avian, mammalian, and human origin, only slow-growing trachoma-inclusion-conjunctivitis agents did not produce plaques. The plaque assay is highly sensitive, reproducible, and offers a potential tool for investigations requiring accurate measurement of small changes in chlamydial infectivity.

Pathogenicity and immunogenic efficacy of a live attentuated plaque vaccine in vervet monkeys.

A live attenuated Yersinia pestis (Pasteurella pestis) vaccine strain designated EV51f, which had been passaged through guinea pigs previously treated with ferrous sulfate, was shown to be pathogenic for African green vervet monkeys (Cercopithecus aethips pygerythrus), but not for guinea pigs. The bacilli multiplied in the monkeys, as shown by positive blood cultures, caused an elevation of white cell counts and rectal temperatures, and resulted in death of 26% (13/50) of animals. Postmortem findings of these animals were typical of bubonic-septicemic plague. This vaccine did not cause deaths in 50 guinea pigs even in doses up to 100 million viable bacilli inoculated subcutaneously. It is suggested that the virulence of an attenuated Y. pestis strain which does not produce pigment on a defined medium containing hemin, but possesses all other known virulence determinants, is dependent on the availability of iron in vivo. The serological response of the monkeys as determined by the hemagglutinating and mouse protective antibodies was high one month after vaccination and also in guinea pigs, as shown by virulent challenge. This antibody level declined in monkeys over a period of nearly 6 months, and a decline in immunity was confirmed by virulent challenge which resulted in the death of 30% of vaccinated monkeys. The level of immunity in monkeys did not appear to be related to the dose of vaccine.

Plaque reduction technique for demonstrating neutralizing antibodies for Chlamydia.

Some members of the genus Chlamydia (Bedsonia or psittacosis-lymphogranuloma venereum-trachoma-inclusion conjunctivitis group of microorganisms) produce plaques in monolayers of mouse fibroblast (L-929) cells. Hyperimmune chicken antisera may be capable of specifically reducing plaque counts. When the test was applied to chlamydiae isolated from avian species, the results indicated that different isolates with a common source had similar antigenic reactivity. The plaque reduction test is a potentially useful method for serotyping chlamydiae. The difficult aspect of the method appears to be a readily reproducible means of producing neutralizing antiserum.

Serotyping of Chlamydia: isolates of bovine origin.

Chlamydial isolates of bovine origin were serotyped by a plaque reduction method. Of the two major serotypes observed, type 1 included isolates from bovine abortion and enteric infections, whereas type 2 isolates were associated with polyarthritis or encephalomyelitis. These two serotypes were identical to those with a similar disease distribution previously observed in isolates of ovine origin. The two groups did not cross-react and they were serologically unrelated to chlamydiae of avian origin. Thus, it appears that many chlamydial isolates causing intestinal infections or abortion in sheep or cattle are closely related antigenically, as are those producing polyarthritis, encephalomyelitis, and conjunctivitis, and that the two groups are distinct.

Serotyping of Chlamydia. I. Isolates of ovine origin.

Eight chlamydial isolates of ovine origin were tested in a plaque reduction system using homologous and heterologous rooster antisera. The eight isolates could be separated into two separate immunotypes. Type 1 included isolates associated with ovine abortion and one agent recovered from the feces of an apparently normal sheep. Type 2 isolates were associated with polyarthritis and conjunctivitis. These two serotypes were not cross-reactive with several chlamydiae of avian origin. Further application of the plaque reduction test may provide a useful means of typing chlamydiae.

The exstrophy-epispadias complex: is aesthetic appearance important?

OBJECTIVE: To show the relevance of cosmetic appearance in the adequate treatment of patients with exstrophy-epispadias complex (EEC), and to indicate that surgery by experienced teams can improve the long-term treatment forecast and the patient's body image. PATIENTS AND METHODS: From 1978 to 2002, 71 patients diagnosed with EEC were treated in the authors' institution; 24 (aged 2-23 years) were selected to undergo different surgical procedures. The criterion for surgery considered interviews conducted by the psychology team with the parents and children. The plastic surgery and paediatric urology teams carried out the procedures jointly; the follow-up was 0.33-7 years. RESULTS: Five female patients and six male had abdominoplasty to treat multiple scars; eight had intermittent catheterization conduits repositioned from the right iliac fossa to the umbilicus. Six female patients had plastic surgery of the external genitalia and three had a broad mobilization of the urogenital sinus. Thirteen male patients had a small penis and had the corpora cavernosa fully mobilized and the penis reconstructed. Five female patients and one male had anterior osteotomy. One patient with no left testis had it replaced and one patient with uterine prolapse had the uterus fixed to the posterior abdominal wall. Six patients had a second procedure, in two because the outcome of the initial operation was poor and in the others to complement the initial treatment. In all but one patient there was an improvement in the objective criteria, e.g. school absences, difficulty in establishing long-lasting social relationships and refusal to participate in sports activities. However, none of the patients would attempt sexual intercourse. CONCLUSIONS: Body image, self-esteem, sexuality, sexual function and fertility are deemed crucial by adolescents; in patients with EEC customised surgical procedures can give a satisfactory aesthetic outcome, and be a further reason for adequately following occasional urinary complications and renal function, to avoid loss to follow-up.

Chlamydial infection in women with cervical dysplasia.

The prevalence of antibodies to chlamydiae, particularly to TRIC (trachoma-inclusion conjunctivitis) agents, was studied in women with cervical dysplasia and in women attending selected clinics (obstetrics, cancer-screening, and gynecology). In addition, attempts were made to isolate TRIC agents and herpesviruses from the cervices of these women. TRIC agent recovery rates 4.1 per cent for women with dysplasia, 5.4 per cent for pregnant women, 7.8 per cent in the women's clinic, and 0.8 per cent in the cancer-screening clinic. Herpesvirus recovery rates were lower, on the order of 1 per cent or less in each clinic. Complement-fixing antibodies to chlamydial group antigen were detected in 21.5 per cent of women with dysplasia. With a more sensitive fluorescent antibody method, 77.6 per cent of the women with dysplasia or cervical cancer were shown to have antibodies to chlamydiae. In general, antichlamydial antibodies were less prevalent in the other clinic populations. The results of this study indicate that women with cervical dysplasia or cancer may have a high prevalence of antibodies to sexually transmitted agents other than herpesvirus type 2.