Ontogeny of the nasopalatine duct in primates

Ecological explanations have been put forward to account for the precocious or delayed development of patency in ducts leading to the vomeronasal organ (VNO) in certain mammals. Perinatal function may be related, in part, to the patency or fusion of the vomeronasal and nasopalatine (NPD) ducts. However, few studies have focused on NPD development in primates, which generally have a prolonged period of dependence during infancy. In this study we examined 24 prenatal primates and 13 neonatal primates, and a comparative sample of fetal mice and insectivores. In embryonic and early fetal Microcebus murinus, the NPD was completely fused, whereas in fetuses of later stages the duct was partially fused or completely patent. M. myoxinus of all stages demonstrated some degree of NPD fusion. In all other prenatal primates, the NPD was fused to some extent. Four prenatal insectivores (Tenrec ecaudatus) showed some degree of NPD fusion. In Mus musculus at 19 days gestation, the NPD was patent, although the anatomically separate VNO duct was fused. T. ecaudatus and most of the neonatal primates revealed complete NPD patency. An exception was Saguinus geoffroyi, which exhibited fusion of the NPD near the VNO opening. These observations may relate to differences in perinatal VNO function. The differences noted in our study suggest that M. murinus and M. myoxinus may differ in perinatal VNO functionality and perhaps in related behavior. Observations of neonatal primates suggest that NPD patency may be relatively common at birth and could serve other purposes in addition to being an access route for VNO stimuli.     

Intranasal vaccination induces protective immunity against intranasal infection with virulent Francisella tularensis biovar A

The inhalation of Francisella tularensis biovar A causes pneumonic tularemia associated with high morbidity and mortality rates in humans. Exposure to F. tularensis usually occurs by accident, but there is increasing awareness that F. tularensis may be deliberately released in an act of bioterrorism or war. The development of a vaccine against pneumonic tularemia has been limited by a lack of information regarding the mechanisms required to protect against this disease. Vaccine models for F. tularensis in inbred mice would facilitate investigations of the protective mechanisms and significantly enhance vaccine development. Intranasal vaccination with the attenuated live vaccine strain (LVS) of F. tularensis reproducibly protected BALB/c mice, but not C57BL/6 mice, against intranasal and subcutaneous challenges with a virulent clinical isolate of F. tularensis biovar A (NMFTA1). The resistance of LVS-vaccinated BALB/c mice to intranasal NMFTA1 challenge was increased 100-fold by boosting with live NMFTA1 but not with LVS. The protective response was specific for F. tularensis and required both CD4 and CD8 T cells. The vaccinated mice appeared outwardly healthy for more than 2 months after NMFTA1 challenge, even though NMFTA1 was recovered from more than half of the vaccinated mice. These results show that intranasal vaccination induces immunity that protects BALB/c mice from intranasal infection by F. tularensis biovar A.     

Mass spectrometric identification of mtb81, a novel serological marker for tuberculosis

We have used serological proteome analysis in conjunction with tandem mass spectrometry to identify and sequence a novel protein, Mtb81, which may be useful for the diagnosis of tuberculosis (TB), especially for patients coinfected with human immunodeficiency virus (HIV). Recombinant Mtb81 was tested by an enzyme-linked immunosorbent assay to detect antibodies in 25 of 27 TB patients (92%) seropositive for HIV as well as in 38 of 67 individuals (57%) who were TB positive alone. No reactivity was observed in 11 of 11 individuals (100%) who were HIV seropositive alone. In addition, neither sera from purified protein derivative (PPD)-negative (0 of 29) nor sera from healthy (0 of 45) blood donors tested positive with Mtb81. Only 2 of 57 of PPD-positive individuals tested positive with Mtb81. Sera from individuals with smear-positive TB and seropositive for HIV but who had tested negative for TB in the 38-kDa antigen immunodiagnostic assay were also tested for reactivity against Mtb81, as were sera from individuals with lung cancer and pneumonia. Mtb81 reacted with 26 of 37 HIV(+) TB(+) sera (70%) in this group, compared to 2 of 37 (5%) that reacted with the 38-kDa antigen. Together, these results demonstrate that Mtb81 may be a promising complementary antigen for the serodiagnosis of TB.     

Searching for answers: How well do depression websites answer the public’s questions about treatment choices?

Objective

The purpose of this study was to evaluate websites providing information on treatment for depression to the public, and to evaluate changes in the quality of website information over time.

Quantitative measurement of IgE antibodies to purified allergens using streptavidin linked to a high-capacity solid phase

BACKGROUND: Commercially available assays for IgE antibody provide results in international units per milliliter for many allergen extracts, but this is not easily achieved with purified or novel allergens. OBJECTIVE: To develop assays for IgE antibody suitable for purified or novel allergens by using a commercially available immunosorbent. METHODS: Streptavidin coupled to a high-capacity immunosorbent (CAP) was used to bind biotinylated purified allergens from mite (Der p 1 and Der p 2), cat (Fel d 1), and dog (Can f 1). Assays for IgE antibody to these allergens were performed on sera from children (asthma and control) as well as adults with atopic dermatitis. RESULTS: The results were validated by serial dilution of sera with high and low levels of IgE antibody and were quantitated in international units per milliliter by using a standard curve. Values for IgE antibody to Der p 1, Der p 2, and Fel d 1 correlated with values obtained with the allergen extracts (r2 = 0.80, 0.84, and 0.95, respectively; P < .001 in each case). Furthermore, the values for IgE antibody in sera from children with high exposure to mite and cat allergens demonstrated 10-fold higher levels of IgE antibody to Der p 1 and Der p 2 than to Fel d 1 (P < .001). CONCLUSION: The streptavidin immunosorbent technique provides a new method for quantifying IgE antibody to purified proteins. The results provide evidence about the high quantities of IgE antibody to purified inhalant allergens in patients with atopic dermatitis. In addition, the results demonstrate major differences in IgE antibodies specific for mite and cat allergens among children with high exposure to both allergens.     

Safety of cetirizine in infants 6 to 11 months of age: a randomized,double-blind,placebo-controlled study

BACKGROUND: H(1)-antihistamines are widely used for symptom relief in allergic disorders in infants and children; however, there are few prospective, randomized, double-blind, controlled studies of these medications in young children, and to date, no such studies have been conducted in infants. OBJECTIVE: This prospective, randomized, parallel-group, double-blind, placebo-controlled study was designed to evaluate the safety of the H(1)-antihistamine cetirizine, particularly with regard to central nervous system and cardiac effects, in infants age 6 to 11 months, inclusive. METHODS: Infants who met the entry criteria for age and had a history of treatment with an H(1)-antihistamine for an allergic or other disorder were randomized to receive 0.25 mg/kg cetirizine orally or matching placebo twice daily orally for 1 week. RESULTS: The mean daily dose in cetirizine-treated infants was 4.5 +/- 0.7 mg (SD). No differences in all-cause or treatment-related adverse events were observed between the cetirizine- and placebo-treated groups. A trend was observed toward fewer adverse events and sleep-related disturbances in the cetirizine group compared with the placebo group. No prolongation in the linear corrected QT interval was observed in cetirizine-treated infants compared with either baseline values or with values in placebo-treated infants. CONCLUSIONS: We have documented the safety of cetirizine in this short-term investigation, the first randomized, double-blind, placebo-controlled study of any H(1)-antihistamine in infants. Additional prospective, randomized, double-blind, placebo-controlled, long-term studies of cetirizine and other H(1)-antihistamines are needed in this population.     

Neu–Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: The utility of exome sequencing in deciphering the diagnosis

Neu–Laxova syndrome (NLS) is a lethal autosomal recessive microcephaly syndrome associated with intrauterine growth restriction (IUGR) and multiple congenital anomalies. Clinical features include central nervous system malformations, joint contractures, ichthyosis, edema, and dysmorphic facial features. Biallelic pathogenic variants in either the PHGDH or PSAT1 genes have been shown to cause NLS. Using exome sequencing, we aimed to identify the underlying genetic diagnosis in three fetuses (from one family) with prenatal skin edema, severe IUGR, micrognathia, renal anomalies, and arthrogryposis and identified a homozygous c.1A>C (p.Met1?, NM_006623.3) variant in the PHGDH gene. Loss of the translation start codon is a novel genetic mechanism for the development of NLS. Prenatal diagnosis of NLS is challenging and few reports describe the fetal pathology. Fetal neuropathologic examination revealed: delayed brain development, congenital agenesis of the corticospinal tracts, and hypoplasia of the hippocampus, cerebellum and brainstem. Each pregnancy also showed increased nuchal translucency (NT) or cystic hygroma. While NLS is rare, it may be a cause of recurrent increased NT/cystic hygroma. This finding provides further support that cystic hygroma has many different genetic causes and that exome sequencing may shed light on the underlying genetic diagnoses in this group of prenatal patients.     

Discriminatory power and reproducibility of novel DNA typing methods for Mycobacterium tuberculosis complex strains

In recent years various novel DNA typing methods have been developed which are faster and easier to perform than the current internationally standardized IS6110 restriction fragment length polymorphism typing method. However, there has been no overview of the utility of these novel typing methods, and it is largely unknown how they compare to previously published methods. In this study, the discriminative power and reproducibility of nine recently described PCR-based typing methods for Mycobacterium tuberculosis were investigated using the strain collection of the interlaboratory study of Kremer et al. This strain collection contains 90 M. tuberculosis complex and 10 non-M. tuberculosis complex mycobacterial strains, as well as 31 duplicated DNA samples to assess reproducibility. The highest reproducibility was found with variable numbers of tandem repeat typing using mycobacterial interspersed repetitive units (MIRU VNTR) and fast ligation-mediated PCR (FLiP), followed by second-generation spoligotyping, ligation-mediated PCR (LM-PCR), VNTR typing using five repeat loci identified at the Queens University of Belfast (QUB VNTR), and the Amadio speciation PCR. Poor reproducibility was associated with fluorescent amplified fragment length polymorphism typing, which was performed in three different laboratories. The methods were ordered from highest discrimination to lowest by the Hunter-Gaston discriminative index as follows: QUB VNTR typing, MIRU VNTR typing, FLiP, LM-PCR, and spoligotyping. We conclude that both VNTR typing methods and FLiP typing are rapid, highly reliable, and discriminative epidemiological typing methods for M. tuberculosis and that VNTR typing is the epidemiological typing method of choice for the near future.