The influence of treating ferret influenza antisera with enzymes of crude filtrate ofVibrio cholerae on the titre of the antibodies

Summary After treating influenza antisera from ferrets with enzymes of a crude filtrate ofVibrio cholerac (pH 7.6) for the purpose of eliminating the non-specific inhibitors it is not possible to detect a significant fall in the titre of the antibodies with the aid of the egg protection test. Financial support was provided by the Institute for Preventive Medicine, Leyden; N. V. Philips Roxane, Weesp; the State Department of Science; the Jan Dekker Fund, and the Cura?ao Fund the Preventive Medicine.     

Studies on the antigenic behaviour of egg- and egg-mouse-egg-lines of strains of influenza virus,with the aid of the haemagglutination-inhibition test

Summary Egg- and egg-mouse-egg-lines of strains of influenza virus were compared with the aid of the haemagglutination inhibition test. In most experiments it was found that the crossing of an antiserum of an egg-mouse-egg-line against the homologous egg-line or against a heterologous egg-line of a strain belonging to the same subgroup yields a low or very low antititre. We are indebted to DrG. K. Hirst (New York) and DrJ. Y. Sugg (New York) for sending us the strains of influenza virus Ala and Cam. Financial support was provided by the Institute for Preventive Medicine, Leyden; N. V. Philips Roxane, Weesp; the State Department of Science; the Jan Dekker Fund, and the Cura?ao Fund for Preventive Medicine.     

Studies on the elimination of non-specific inhibitors in sera against influenza viruses with the aid of filtrates ofVibrio cholerae

Summary In the sera of humans and various animals there are two different non-specific inhibitors (α-and β-inhibitors) which may be specifically abolished by two substances (α-and β-“enzymes”) both present in filtrates ofV. cholerae. This neutralization is necessary for the rapid classifying of influenza virus strains with the aid of the haemagglutination inhibition test. The egg line strains of the A- and A′-groups are only sensitive to β-inhibitor, while the mouse line strains of the same groups are only sensitive to the α-inhibitor. This does not apply to strains of the B group, where mouse as well as egg lines are sensitive to both inhibitors. With the aid of isolated β-inhibitor (easily to be prepared from cattle serum), it is possible to decide in a quick manner whether or not a strain from the A- or A′-group has previously been adapted to the mouse. With the technical assistance of Miss I.de Nooyer and with the financial support provided by the Institute for Preventive Medicine, Leyden; N.V. Philips Roxane, Weesp; the State Department of Science; the Jan Dekker Fund, and the Curacao Fund for Preventive Medicine.     

Antibody response against strains of influenza-A virus in ferrets with basic immunity

Summary In Holland ferrets are offered for sale with basic antibodies against one or more sub-groups of strains of influenza-A virus. With the haemagglutination inhibition test low basic antibody titers can only be detected by neutralising the non-specific inhibitor in the ferret sera. When such a ferret is infected with a strain of a heterologous sub-group, a considerable rise in antibodies is obtained against the homologous and heterologous sub-groups. It is very probable that the same holds for human beings. Some examples are given of haemagglutination-inhibition tests with serum pairs from adults who suffered from influenza in the epidemic of the winter of 1949 in Holland from which the non-specific inhibitor had been eliminated.Sub-unit of the Influenza Research Team of the Institute of Preventive Medicine, Leyden. With the financial support of the Institute of Preventive Medicine, the Department of Medical Research Philips Roxane (Weesp), the State Department of Science, and the Jan Dekker Fund.     

Mucosal but Not Parenteral Immunization with Purified Human Papillomavirus Type 16 Virus-Like Particles Induces Neutralizing Titers of Antibodies throughout the Estrous Cycle of Mice

We have recently shown that nasal immunization of anesthetized mice with human papillomavirus type 16 (HPV16) virus-like particles (VLPs) is highly effective at inducing both neutralizing immunoglobulin A (IgA) and IgG in genital secretions, while parenteral immunization induced only neutralizing IgG. Our data also demonstrated that both isotypes are similarly neutralizing according to an in vitro pseudotyped neutralization assay. However, it is known that various amounts of IgA and IgG are produced in genital secretions along the estrous cycle. Therefore, we have investigated how this variation influences the amount of HPV16 neutralizing antibodies induced after immunization with VLPs. We have compared parenteral and nasal protocols of vaccination with daily samplings of genital secretions of mice. Enzyme-linked immunosorbent assay analysis showed that total IgA and IgG inversely varied along the estrous cycle, with the largest amounts of IgA in proestrus-estrus and the largest amount of IgG in diestrus. This resulted in HPV16 neutralizing titers of IgG only being achieved during diestrus upon parenteral immunization. In contrast, nasal vaccination induced neutralizing titers of IgA plus IgG throughout the estrous cycle, as confirmed by in vitro pseudotyped neutralization assays. Our data suggest that mucosal immunization might be more efficient than parenteral immunization at inducing continuous protection of the female genital tract.     

Effect of human nasal secretions on the antiviral activity of human fibroblast and leukocyte interferon.

Many normal human nasal secretions contain an inhibitor of human fibroblast IF. This inhibitor had no effect on human leukocyte IF. The amount of inhibition of fibroblast IF increased with increasing quantities of nasal secretions. Also, the inhibition could be overcome with increasing concentrations of IF.     

变应性鼻炎鼻分泌物中细胞内DNA和RNA代谢的观测

本文介绍应变性鼻炎鼻分泌物中细胞内DNA和RNA代谢变化的观测方法。以鼻分泌物中的多种炎性细胞为实验标本,经细胞贴壁、0.1%吖橙染色标记,37℃孵育15min;采用激光扫描共聚焦显微镜对细胞内DNA,RNA形态和含量进行观测。结果表明：本方法应用于变应性鼻炎鼻分泌物细胞内DNA、RNA代谢的研究是切实可行的。     

Evidence for mating plugs in the fire ant <Emphasis Type="Italic">Solenopsis invicta</Emphasis>

Summary Male inhibition of female re-mating is com-mon in many insects. Mating plugs, used by males to con-trol female re-mating, have been postulated in several ant species. Recent studies of bumblebees have described re-mating inhibition by male accessory gland secretions. Fire ants Solenopsis invicta possess accessory glands containing the same four fatty acids as do the bumblebees. Furthermore it appears that some of these acids are transferred to the female at mating. Thus, it is possible that single mating of fire ant females may be enforced by male mating plugs.     

Trachea,lung, and tracheobronchial lymph nodes are the major sites where antigen-presenting cells are detected after nasal vaccination of mice with human papillomavirus type 16 virus-like particles

Vaccination by the nasal route has been successfully used for the induction of immune responses. Either the nasal-associated lymphoid tissue (NALT), the bronchus-associated lymphoid tissue, or lung dendritic cells have been mainly involved. Following nasal vaccination of mice with human papillomavirus type 16 (HPV16) virus-like-particles (VLPs), we have previously shown that interaction of the antigen with the lower respiratory tract was necessary to induce high titers of neutralizing antibodies in genital secretions. However, following a parenteral priming, nasal vaccination with HPV16 VLPs did not require interaction with the lung to induce a mucosal immune response. To evaluate the contribution of the upper and lower respiratory tissues and associated lymph nodes (LN) in the induction of humoral responses against HPV16 VLPs after nasal vaccination, we localized the immune inductive sites and identified the antigen-presenting cells involved using a specific CD4(+) T-cell hybridoma. Our results show that the trachea, the lung, and the tracheobronchial LN were the major sites responsible for the induction of the immune response against HPV16 VLP, while the NALT only played a minor role. Altogether, our data suggest that vaccination strategies aiming to induce efficient immune responses against HPV16 VLP in the female genital tract should target the lower respiratory tract.     

Comparison of the response to histamine challenge of the nose and the maxillary sinus: effect of loratadine.

To study the response of the maxillary sinus to histamine provocation, we performed a double-blind, randomized, crossover trial during which nonallergic subjects without symptoms of rhinitis (n = 25) received either 10 mg loratadine or placebo once daily for a week and then underwent nasal challenge with histamine (3, 10, and 30 mg/ml) followed, 24 h later, by a maxillary sinus challenge while still receiving the medication. Nasal challenge with histamine led to significant increases in vascular permeability, reflex nasal secretions, sneezing, and other nasal symptoms. Sinus challenge resulted in significant increases in vascular permeability within the sinus cavity (P < 0.01) and some nasal symptoms but no significant change in reflex nasal secretions. The response of the sinus mucosa to histamine was lower in magnitude than that of the nose. Treatment with loratadine resulted in a significant inhibition of the histamine-induced changes in both nasal and sinus cavities. Our data suggest the lack of a sinonasal reflex response to histamine provocation of the maxillary sinus of nonallergic individuals.     

Immunological reactions in the secretions of volunteers vaccinated against influenza by aerosol and intranasally]

Aerosol and intranasal methods of influenza vaccination were studied on volunteers. Aerosol vaccination induced intensive S-IgA-producing reaction and increase of the specific antibody titres in the saliva and nasal secretions. Intranasal vaccination led to increase of influenza antibodies in the washings from the nasopharynx. The presence of a wide spectrum of antiviral and antibacterial normal secretory antibodies was revealed in the fluids under study. Along with stimulation of specific secretory antibodies, the methods of influenza vaccination under study led to increase of the titre of antibodies nonspecific of the vaccine used.     

New ways to go—nasal floor structures as channelling system for vomeronasal stimuli in the shrew (<Emphasis Type="Italic">Sorex araneus</Emphasis>, Mammalia)

The mammalian lateral nasal gland (LNG, also called Steno’s gland) is known to be one source of so-called odorant-binding proteins, which are suggested to work as vehicles to carry chemosensory stimuli within the nasal cavity in order to guide them to olfactory and vomeronasal sensory neurons. Up to now, a largely unattended and unanswered question is how the secretions of the LNG migrate between the glandular opening at the upper edge of the anterior lateral nasal wall and the more caudally located vomeronasal organ. In order to address this issue, the functional morphology of the rostral nasal cavity of Sorex araneus was investigated histologically. Special interest was laid on the opening region of the LNG in the vestibular region of the nose and its topological connection to a hitherto largely unnoticed nasal concha, the atrioturbinate. It appears that the atrioturbinate serves as a specialised channel that directs the secretions of the LNG pointedly towards the entrance of the vomeronasal organ. In addition, it was observed that—contrary to previous reports—the LNG in Sorex araneus is anatomically clearly separated from the maxillary sinus gland and does not invade the maxillary sinus.     

Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice

Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG⁺ and IgA⁺ antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge.     

Relationship and possible function of the nasal sacs and glands of the one-humped camel, camelus dromedarius.

The relationship between the lateral nasal gland and sacs of the maxillary recesses was investigated. The nasal sacs possess a well-defined aperture communicating with the nasal cavities. It was concluded that the sacs and not the body of the gland produce mucous secretions that moisten the inhaled dry air of the desert and may also act as reservoirs. A possible function of the body of the nasal gland is water economy by excretion of concentrated salts.     

Missed opportunities for prevention in general internal medicine

BACKGROUND: According to the Canadian Society of Internal Medicine, the Canadian general internist is in the ideal position to promote patient health through disease prevention. To explore the general internist''s contribution to disease prevention, the authors quantified the extent to which opportunities for prevention were addressed by the general internal medicine (GIM) service in an acute care teaching hospital in Calgary. METHODS: The authors interviewed 100 adult patients before discharge from the hospital''s GIM service between May 14, 1997, and Dec. 2, 1997. The number of potential opportunities for preventive intervention were identified for each patient from 10 possible interventions recommended by the Canadian Task Force on the Periodic Health Examination (now the Canadian Task Force on Preventive Health Care): breast cancer screening, Papanicolaou smear for cervical cancer, counselling on menopausal hormone replacement therapy, digital rectal examination for prostate cancer, smoking cessation counselling, cholesterol measurement, therapy or monitoring for hypertension, influenza vaccination, pneumococcal vaccination and colorectal cancer screening. The authors determined which interventions the patient had undergone before the current admission to hospital and, using patient recall and postdischarge medical chart review, which opportunities for intervention were addressed by the GIM service during the current admission. An opportunity for preventive intervention was considered as addressed by the GIM service if it was performed during the current admission or if the general internist informed the patient or the patient''s family physician of the need for such intervention in the near future. RESULTS: Among the 10 preventive interventions considered, a mean of 3.8 potential opportunities for prevention were identified for each patient. Of these, 46.5% had been addressed before the current admission, and 8.7% were addressed by the GIM service during the admission. Therefore, at the time of discharge, a mean of 55.2% of opportunities had been addressed. Among the opportunities not previously addressed, the GIM service most frequently addressed digital rectal examination for prostate cancer and cholesterol measurement. INTERPRETATION: General internists are discharging patients without sufficiently addressing opportunities for disease prevention. Preventive care protocols may be needed to limit the frequency of missed opportunities for prevention in patients admitted to tertiary care GIM services.     

Selection of the most efficacious of twenty-two inactivated Sendai virus nasal vaccines by determination of the protection index in mice.

BACKGROUND AND PURPOSE: Sendai virus nasal vaccines inactivated with various chemicals induce complete protection against contact-challenge exposure with the Nagoya strain. The study reported here was to reevaluate the efficacy of the inactivants by determining the protective index (PI) in mice, using the more virulent MN strain. METHODS: Mice were given each of 22 inactivated vaccines intranasally three times. After challenge exposure with 10(-2) to 10(6) MID50 of virus, infection of cells of the respiratory tract was determined by immunofluorescence. RESULTS: Twelve vaccines induced PI > or = 2.0 in the nasal mucosa and were classified as group 1. The first half of the preceding vaccines that induced PI > or = 3.2 in the larynx were classified subgroup a, and the rest were classified subgroup b. Of the other 10 vaccines, 6 that induced PI < or = 2.0 in the larynx and 4 that induced intermediate PI in the nasal mucosa and larynx were ranked as groups 3 and 2, respectively; PI of the trachea decreased by numeric order of groups. Serum hemagglutination inhibition titer induced by intranasal vaccination was low in general. CONCLUSION: On the basis of PI values, 6 of the 22 nasal vaccines provided the strongest defense in the respiratory tract.     

Intranasal vaccination with a recombinant vesicular stomatitis virus expressing cottontail rabbit papillomavirus L1 protein provides complete protection against papillomavirus-induced disease

Immunizations with live recombinant vesicular stomatitis viruses (rVSV) expressing foreign viral proteins have successfully protected animals from challenges with several heterologous viruses. We developed an rVSV expressing the major capsid protein (L1) of cottontail rabbit papillomavirus (CRPV) and tested the efficacy of protection following CRPV challenge. An rVSV expressing L1 of CRPV (VSV-L1) was characterized for the protective ability afforded by intranasal, intradermal, or intramuscular vaccination in rabbits subsequently challenged with CRPV. Protein expression of L1 in VSV-L1 was confirmed by radioimmunoprecipitation assays. Nuclear localization of L1 was demonstrated by indirect immunofluorescence assays. Immunized rabbits elicited significant VSV neutralization and VLP-L1 enzyme-linked immunosorbent assay titers. VSV-L1 vaccination was not associated with weight loss or any other adverse clinical signs in the rabbit model. VSV shedding in nasal secretions occurred in some rabbits, peaking at 4 to 6 days after intranasal vaccination, with no further shedding after day 6. Specific humoral immunity to the L1 protein was consistently seen after a single VSV-L1 vaccination when administered through an intradermal or intramuscular route or after a boost via the intranasal route. Rabbits were completely protected from CRPV-induced papillomas after VSV-L1 vaccination and boost given intranasally or intramuscularly. Vaccination with VSV-L1 is a novel approach to prevent papillomavirus-induced disease and demonstrates a potential strategy for developing a human papillomavirus vaccine that can be given without injection.     

Enhanced mucosal immunoglobulin A response of intranasal adenoviral vector human immunodeficiency virus vaccine and localization in the central nervous system

Replication-defective adenovirus (ADV) vectors represent a promising potential platform for the development of a vaccine for AIDS. Although this vector is typically administered intramuscularly, it would be desirable to induce mucosal immunity by delivery through alternative routes. In this study, the immune response and biodistribution of ADV vectors delivered by different routes were evaluated. ADV vectors expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pol, and Env were delivered intramuscularly or intranasally into mice. Intranasal immunization induced greater HIV-specific immunoglobulin A (IgA) responses in mucosal secretions and sera than in animals with intramuscular injection, which showed stronger systemic cellular and IgG responses. Administration of the vaccine through an intranasal route failed to overcome prior ADV immunity. Animals exposed to ADV prior to vaccination displayed substantially reduced cellular and humoral immune responses to HIV antigens in both groups, though the reduction was greater in animals immunized intranasally. This inhibition was partially overcome by priming with a DNA expression vector expressing HIV-1 Gag, Pol, and Env before boosting with the viral vector. Biodistribution of recombinant adenovirus (rADV) vectors administered intranasally revealed infection of the central nervous system, specifically in the olfactory bulb, possibly via retrograde transport by olfactory neurons in the nasal epithelium, which may limit the utility of this route of delivery of ADV vector-based vaccines.     

Production of glycoprotein by Candida albicans in a synthetic medium and its influence on the growth of newborn mice

Summary Growth ofCandida albicans on a synthetic medium for a period of 6 weeks produces glycoprotein substance in the approximate amount of 150 mg per liter. The polysaccharide component is formed by glucose and mannose in the approximate ratio 3:1. The protein component is composed of at least 15 different amino acids. Half percent of glucosamine was also found. The glycoprotein substance is water soluble and toxic to Swiss mice. LD50 is 0.75 mg/g of body weight when injected intravenously. Subcutaneous injection to newborn Swiss mice produced inhibition of growth. The degree of inhibition varied with the dosage. On one occasion when using a small amount of compound, stimulation of growth was also seen.This work was supported by Damon Runyon Memorial Fund Grant 720 and Joan Sloan Memorial Fund.     

Identification of 2-phenylethanol with a rose-like odor from anal sac secretions of the small Indian mongoose (Herpestes auropunctatus)

The small Indian mongoose (Herpestes auropunctatus) is an invasive species in Okinawa and Amami-Oshima, Japan. Major strategies for their eradication have been the use of baited traps, which suffer from decreasing efficiency with declining populations and the bycatch of native animals. To address these concerns, mongoose-specific lures are required. In this study, we aimed to identify species- and/or sex-specific compounds from anal sac secretions of small Indian mongooses. Volatile compounds emitted from male and female mongoose anal sac secretions were analyzed by thermal desorption-gas chromatography-mass spectrometry. In addition to several fatty acids, 2-phenylethanol was identified as a minor compound, which is uncommon in mammalian secretions but a dominant odorant in roses. Female samples emitted higher levels of 2-phenylethanol than male samples did. These findings indicate that 2-phenylethanol is a female-specific volatile compound of anal sac secretions in small Indian mongooses, and it may be useful as an ingredient of mongoose-specific scent lures.