Prenatal survival of mouse embryos irradiated in utero with fission neutrons or 250 kV X-rays during the two-cell stage of development.

PURPOSE: To investigate the relationship between radiation dose at the two-cell stage and prenatal survival. MATERIALS AND METHODS: Pregnant mice were irradiated with fast neutrons (0.53-1.94 Gy) or X-rays (1.50-5.00 Gy), or sham irradiated. At selected times up to gestation day 16, the mice were killed and the uterine contents examined. RESULTS: At doses up to 0.82 Gy of neutrons and 2.50 Gy of X-rays, all or virtually all the radiation-induced deaths occurred during the period from the time of implantation to gestation day 10. At higher doses an appreciable proportion of the deaths occurred after day 10. Many neutron-induced deaths in the period from implantation to day 10 occurred before day 7. A mathematical model was developed for estimating survival to gestation day 16 as a function of neutron dose. CONCLUSIONS: The mortality pattern, in which low radiation doses led to early deaths and high doses to both late and early deaths, suggests the existence of two lethal processes. The relationship between neutron dose and survival to gestation day 7 has been interpreted as indicating that the early deaths involved predominantly a two-event inactivation mechanism. An individual cell of a two-cell embryo was found to be less sensitive to lethal radiation injury than a pronuclear zygote.

Bilateral root or root canal aberrations in a dental school patient population.

Clinicians have often noted that aberrant root morphology in a given tooth is also observed with varying degrees of frequency in the corresponding contralateral tooth. The purpose of this study was to determine the proportion of bilateral morphological root aberrations in a random sample of adult human dentition. Five hundred one dental records were selected from the retired record section at the University of Oklahoma College of Dentistry and their full-mouth radiographs were reviewed for aberrant root canal morphology. Bifurcation of the canal in mandibular first premolars was the most common finding (22.8% of patients), with 60% of these being bilateral. Maxillary anterior teeth had the least aberrations. It was observed that unusual root morphology is bilateral approximately 60% of the time. Therefore, the incidence of root or root canal abnormalities reported by the percentage of patients involved will always exceed the incidence of abnormalities reported by type of tooth (e.g. mandibular or canine) involved except for abnormalities which are found bilaterally in 100% of the patients studied. Radiographic interpretation appears to result in a lower incidence of anatomical aberrations than direct identification. The more rare the aberration, the more likely it is to be bilateral in occurrence.

The health agency training program: continuing education courses in biostatistics and epidemiology.

The authors describe the development and evaluation of a continuing education program in biostatistics and epidemiology. Short courses were presented to public health and mental health professionals using teaching strategies that included lecture, discussion, practice-oriented examples, and interactive problem-solving. A total of 1723 health professionals attended one or more of the 120 courses presented from 1992 to 1996 in seven US states. Most course participants were female: the highest education level for 40% was a bachelor's degree, while 42% had advanced degrees. Approximately 66% of participants signed up for continuing education credits. The program represents a successful partnership between an academic institution and health agencies in a seven-state region.

The relation between newborn hemoglobin F fractions and risk factors for sudden infant death syndrome.

OBJECTIVES: The aims of this study were to determine and compare fetal hemoglobin (HbF) fractions at birth in newborns exposed and not exposed to selected factors that have been reported to increase the risk of sudden infant death syndrome (SIDS). Previous studies have implicated HbF in the etiology of SIDS by finding higher fractions in infants dying from SIDS compared to age-matched control infants. DESIGN: We performed a cross-sectional study using high-performance liquid chromatography to measure HbF fractions in newborn cord blood samples. Exposure to selected risk factors for SIDS was assessed through review of medical records. PARTICIPANTS: Six hundred thirty-three infants born at Via Christi Regional Medical Center-St Francis Campus, Wichita, Kan, from February 28 through August 5, 1997. MAIN OUTCOME MEASURE: Hemoglobin F fractions at birth were compared in newborns exposed and not exposed to selected risk factors associated with increased incidence of SIDS. RESULTS: Mean HbF fractions were significantly higher in preterm newborns of mothers who smoked and in term newborns with intrauterine growth restriction, pregnancy weight gain less than or equal to 9 kg, and pregnancy complications associated with reduced placental blood flow. An elevated newborn HbF fraction, defined as 77% or greater, was significantly associated with maternal smoking, maternal anemia, intrauterine growth restriction, and pregnancy complications associated with reduced placental blood flow. CONCLUSION: This study suggests a possible mechanism (HbF) by which previously identified factors may increase the risk of SIDS.

Hymenolepis nana: intestinal tissue phase in actively immunized mice.

We investigated the fate of the intestinal cestode Hymenolepis nana in immunized mice. Immunity was induced by infection with the parasite eggs. These immunized animals and unimmunized controls were then challenged with 50,000 H. nana eggs. The mice were killed 4 to 90 hr after challenge, and H. nana in the intestinal tissue were counted. At 4 hr after challenge the unimmunized and immunized animals had approximately equal numbers of oncospheres. By 12 hr there were fewer parasites in the immunized than in the unimmunized animals. At 90 hr, no H. nana were seen in the immunized mice, whereas in the unimmunized animals the median number of cysticercoids was more than 1,000. It appears, therefore, that in mice well immunized to H. nana by infection, challenge oncospheres can burrow into the intestinal tissue before they are killed. The reduced number of oncospheres in the immunized mice 12 hr after challenge, and the accumulation of eosinophils near individual oncospheres still present, indicate that an immune response to the parasite was taking place. Absence of a lymphocyte infiltration near any of the oncospheres suggests that the mechanism of immunity was not lymphocyte mediated; thus, the histopathology of the reaction is consistent with that of humoral immunity.

Epidemiologic patterns of nosocomial infections in 10 Oklahoma hospitals.

The epidemiology of nosocomial infections was studied for 5 years in 10 Oklahoma hospitals. These were categorized into small and large hospitals. The seven small hospitals averaged 47 beds and the three large hospitals averaged 266 beds. Overall, most of the infected patients were < 5 years of > 60 years of age. Females accounted for the majority of the infections. In general, the three most common sites of infection were the urinary tract, surgical wounds, and the lower respiratory tract. Escherichia coli was the single most frequently identified agent followed by Staphylococcus aureus and Staphylococcus epidermidis. The most frequently reported risk factors among patients acquiring a nosocomial infection were the use of prior antibiotics, indwelling urinary catheters, and intravenous catheters or cut-down. The specific problems associated with nosocomial infections, such as sites of infection, risks of infection, and the types of organisms isolated, essentially had not changed much since the 1960s, the 1970s, and for most of the 1980s.

Secular trends in the prevalence of HIV infection among a population of males with hemophilia, 1988-1997: the Oklahoma Hemophilia Surveillance System.

Tracking the natural history of HIV/AIDS in the hemophilia community is useful for planning future health care needs and for adjusting estimates of the prevalence of hemophilia as the impact of HIV/AIDS wanes over time. The present study was designed to determine the annual prevalence of HIV infection from 1988 through 1997 in a population of males with hemophilia A or B. Data were obtained from the Oklahoma Hemophilia Surveillance System and were limited to individuals who were seen at the Oklahoma Hemophilia Treatment Center. In 1988, the prevalence rate of HIV infection was 34 percent. Rates have declined in each subsequent year through 1997. The highest rates of HIV infection were observed in persons with severe hemophilia and hemophilia A. The overall prevalence rates of HIV infection in this treatment center population are lower than those reported in other populations. No new cases of HIV infection were observed in persons with hemophilia born after 1985.

Practice differences between male and female oral and maxillofacial surgeons: survey results and analysis.

PURPOSE: This study describes the personal and practice characteristics of oral and maxillofacial surgeons, with an emphasis on gender differences. Potential explanations for differences found are offered. MATERIALS AND METHODS: A 39-item questionnaire was designed to address areas of suspected differences between male and female oral and maxillofacial surgeons. It included items regarding training, certification, practice type and location, time spent working, practice composition, and personal characteristics. Identical questionnaires were sent to all of the 130 female oral and maxillofacial surgeons (OMSs) registered with AAOMS, as well as to 264 randomly sampled male OMSs. RESULTS: Of the 192 responses received, 109 were from male surgeons, and 83 were from females, 56.8% versus 43.2% of the total. For men, the response rate was 41.3%, whereas the rate was 68.3% for the women; overall, 48.7% of the 394 oral surgeons responded. Profiles of the "average" male and female OMS showed similarities with regard to race, training, and reasons for choosing an OMS career. Age, marital status, number of children, physical characteristics, and use of time outside of work indicated some significant personal differences, as did practice characteristics, including income, number of years in practice, hours spent working, and number of patients seen. Clear gender-based trends were found regarding opinions of physical and mechanical disadvantages, with women more strongly denying such problems. A variety of both positive and negative viewpoints were elicited by the free comment section. CONCLUSIONS: Although male and female OMSs are similar with regard to most variables investigated, some significant differences do exist.

Logistic transmission modeling for the simulated data of GAW10 problem 2.

A recently developed nonparametric method is a generalization of the transmission disequilibrium test across all alleles of a locus. This approach has been applied to Problem 2 of GAW10 and has been extended to explore the combined contribution of neighboring loci for chromosomes 1, 5, and 8. When applied to the chromosome 5 data of the first replicate of the nuclear pedigrees from Problem 2 of GAW10, the data show that four of the 25 loci obtain a probability less than 0.05. However, when combined models composed of each potentially significant marker (p < 0.05) and its nearest neighbors are considered, the combined contributions of G14 and G15 are the most significant (p = 0.007). Consequently, the region near G14 and G15 is identified as the best candidate region in chromosome 5 for linkage to the common disease.

Logistic transmission modeling of simulated data.

A nonparametric method for linkage analysis has been developed and applied to the Problem 1 data set of the Genetic Analysis Workshop 9. Basically, the univariate matched pair strategy of the transmission disequilibrium test has been adapted to multivariate modeling using the conditional logistic function. After setting the critical value for significance at p < or = 0.0001, models at only D5G23 and D1G31 appear to be significant (p < 10(-7)). Logistic transmission modeling is a powerful method for establishing linkage by disequilibrium.

Antibodies to vesicular stomatitis virus proteins in patients with systemic lupus erythematosus and in normal subjects.

OBJECTIVE: To determine the presence of antibodies that bind vesicular stomatitis virus (VSV) proteins in systemic lupus erythematosus (SLE) patient sera, as well as to examine any relationship between antibodies binding the viral nucleocapsid (N) protein and anti-Ro autoantibodies. METHODS: Eighty SLE patient sera, 80 normal control sera, 47 rheumatic disease patient control sera, and 9 sera from Panamanian subjects (6 of whom were infected with VSV) were evaluated by immunoblot of purified VSV proteins. RESULTS: Findings on immunoblots of the Panamanian subjects' sera were consistent with histories of endemic exposure to VSV, as determined by virus neutralization assays. Significantly different binding to viral proteins was seen in the group of 80 SLE patients compared with the normal control group and with the rheumatic disease control group, by a variety of measures. For example, most of the reactivity in the SLE patient sera included binding to the internal viral matrix (M) and N proteins, while the reactivity in the normal control sera was mostly against the surface viral glycoprotein (G) protein alone or the N protein alone. Within this SLE patient cohort, associations were found between binding to N protein and anti-Ro precipitins and between binding to M protein and anti-nuclear RNP autoantibody precipitins. CONCLUSION: The data are consistent with the original specific hypotheses of a relationship between 60-kd Ro autoantigenicity and VSV, as well as with the suggestion that a rhabdovirus may be important in SLE. They do not, however, make possible any conclusions concerning the role of rhabdoviruses in the development of SLE or of anti-Ro autoimmunity.

Autoantibodies to the 20-kDa ribosomal proteins: identification, characterization, and new aspects on prevalence in systemic Lupus erythematosus.

Autoantibodies to the 20-kDa ribosomal proteins (L12/S10) are not well studied, especially in juveniles with systemic lupus erythematosus (SLE). Randomly selected sera from American juveniles and adults with SLE were screened for antibodies to either 20-kDa protein and P proteins and then assayed for anti-L12 and anti-S10 by immunoblot assays. In a pilot study of patients with anti-P (Cohort 1), IgG antibodies to either 20-kDa protein and, specifically, to L12 were observed in 72 and 42% of juveniles and adults, respectively. IgG antibodies to S10 were detected less frequently. In Cohort 2 patients who were chosen irrespective of autoantibody status, twice as many juveniles as adults had IgG antibodies to either 20-kDa protein. Prevalences of IgG anti-L12 and IgG anti-S10 antibodies in the juveniles were 28 and 16% and in the adults were 13 and 12%, respectively. Anti-L12 were strongly but not invariably associated with anti-P, and usually arose temporally to these antibodies. Anti-S10 activity was due to anti-Sm antibodies. We conclude that IgG anti-L12 are more prevalent in SLE than previously reported, and are responsible for the majority of activity toward the 20-kDa ribosomal proteins, especially in juveniles.

Fast-neutron irradiation of mouse embryos in the pronuclear zygote stage: mortality curves and neoplastic diseases in 30-day postnatal survivors.

Mouse embryos in the pronuclear zygote stage were either irradiated in utero with a dose of 15 rad of fast neutrons or were sham-irradiated. Those animals that survived at least 30 days after birth were observed until their natural death. We investigated the percentage incidence and mean age at death for each of the principal neoplastic diseases seen on postmortem examination and also cumulative mortality distributions. No statistically significant differences were found between irradiated and sham-irradiated mice of the same sex.

The presence of masked antiribosomal P autoantibodies in healthy children.

OBJECTIVE: To determine if antiribosomal P (anti-P) autoantibodies are present in healthy children. METHODS: Sera from healthy children were screened for anti-P by conventional enzyme-linked immunosorbent assay and immunoblot techniques. Sera were also treated with immobilized ribosomal P antigens on nitrocellulose strips; affinity-purified fractions were tested for anti-P by high-sensitivity immunoblot. The relative binding affinities were compared for affinity-purified anti-P antibodies from healthy children and adults, and patients with systemic lupus erythematosus. IgG fractions of anti-P-depleted sera from healthy children were assessed for inhibition of autologous anti-P activity. RESULTS: Conventional serologic screening showed no IgG nor IgM anti-P in 88 untreated sera. IgG anti-P were unmasked in all 79 sera treated by the membrane batch affinity technique. IgM anti-P were identified in 27 of the treated sera; the percentage of positive sera decreased with increasing age (chi(2) for linear trend P = 0.00081). Affinity-purified anti-P from children had relative binding affinities similar to those of anti-P from other groups. Sera from healthy children contained inhibitory IgG antibodies to anti-P. CONCLUSION: These results show that anti-P autoantibodies are present in all healthy children. The majority of these autoantibodies are masked by IgG antibodies, suggesting concordant development of a regulatory network.

Familial aggregation of lupus and autoimmunity in an unusual multiplex pedigree.

OBJECTIVE: To evaluate an unusual pedigree with 8 members diagnosed with systemic lupus erythematosus (SLE) METHODS: Pedigree members were evaluated through questionnaires, interviews, and medical records. Sixty members contributed serum samples for autoantibody analysis. RESULTS: The 8 affected females shared several disease features, including arthritis (8/8), antinuclear antibodies (ANA) (8/8), pleuritis (6/8), malar rash (6/8), photosensitivity (5/8), and nephritis (4/8). A total of 15 of 51 (29%) blood relatives had autoantibodies; 9 had autoimmune disease, including 7 with SLE, one with psoriasis, and one with Sjögren's syndrome. Five of 11 (45%) nonconsanguineous spouses also had autoantibodies; one spouse had SLE, and 2 others had thyroid disease. Among 68 spouses of patients with SLE in other pedigrees, only 9 (13%) had autoantibodies, and none were symptomatic (p = 0.02). CONCLUSION: The high rate of autoimmunity among both blood relatives and nonconsanguineous mates in this unusual pedigree suggests a complex interaction of genetic and environmental factors contributing to disease.

The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome 11, and its polymorphisms.

Autoantibodies to Ro/SSA occur in nearly half of the patients with systemic lupus erythematosus and are associated with lymphopenia, photosensitive dermatitis, and pulmonary and renal disease, which suggests that they have an immunopathologic role. The majority of Ro/SSA precipitin-positive patients produce serum antibodies that bind to the 60-kD and 52-kD Ro/SSA proteins. We previously isolated and determined the nucleotide sequence of a cDNA clone that encodes the 52-kD form of the human Ro/SSA protein. In the present study, we have determined the chromosomal location of the gene by in situ hybridization to the end of the short arm of chromosome 11. Hybridization of portions of the cDNA probe to restriction enzyme-digested DNA indicated the gene is composed of at least three exons. The exon encoding the putative zinc fingers of this protein was found to be distinct from that which encodes the leucine zipper. An RFLP of this gene was identified and is associated with the presence of lupus, primarily in black Americans.

Cooperative association of T cell beta receptor and HLA-DQ alleles in the production of anti-Ro in systemic lupus erythematosus.

The immunogenetics of the autoantibody response to Ro (or SS-A) have been explored in patients with systemic lupus erythematous. Data show that alleles of the T cell beta receptor and HLA-DQ loci are cooperatively associated with the presence of anti-Ro autoantibodies in systemic lupus erythematosus. Identification of HLA-DQ by oligonucleotide probe binding to polymerase chain reaction products demonstrates that the combination of DQB1*0201 and one of DQA1*0101, DQA1*0102, or DQA1*0103 is associated with anti-Ro. Patients possessing a particular pair of T cell receptor beta restriction enzyme polymorphisms along with these specific HLA-DQ alleles produce quantitatively more anti-Ro as measured by a sensitive solid-phase immunoassay than patients without these T cell receptor and DQ alleles. Other work has shown that the autoimmune response is directed against the human Ro antigen. These results are consistent with a central role in the disregulation of autoimmunity involving a trimolecular complex composed of the autoantigen bound by a HLA-DQ molecule which, together, are bound in turn by T cells which express a particular subset of T cell receptors.

Confirmation of genetic linkage between human systemic lupus erythematosus and chromosome 1q41.

OBJECTIVE: Genetic susceptibility to systemic lupus erythematosus (SLE) is undoubtedly complex and, presumably, involves multiple loci. Linkage of SLE to D1S229 at chromosome 1q41 has been previously reported in a cohort of 52 affected sibpairs. The present study sought to confirm this reported linkage in an independent cohort of 127 extended multiplex SLE pedigrees containing 107 affected sibpairs. METHODS: Genotype data were collected for D1S229 and 18 flanking microsatellite markers spanning chromosome 1q32-1q42. Analyses of genotype data included a model-based logarithm of odds (LOD) score approach, affected sibpair analyses, and transmission disequilibrium tests. RESULTS: A maximum LOD score of 1.46 was found with D1S229 in a subgroup of 78 European American pedigrees, with additional support from multiple markers clustered around D1S229. Increased allele sharing in affected siblings was most significant at D1S2616, particularly in European Americans (P = 0.0005), followed by D1S229 (P = 0.002), D1S490 (P = 0.028), and D1S1605 (P = 0.037). Although linkage in a subgroup of 40 African American pedigrees was not suggested by the analyses of any marker tested in the chromosomal region surrounding D1S229, a maximum LOD score of 3.03 was found with D1S3462, mapped 15 centimorgans distal to D1S229. CONCLUSION: Our linkage analysis results in European Americans at D1S229 are remarkably similar to those previously reported. That at least 1 genetic effect near this locus is important for susceptibility to lupus should now be generally accepted, and efforts to identify the gene are thereby justified.