Antibody-mediated suppression of grafted lymphoma. IV. Influence of time of tumor residency in vivo and tumor size upon the effectiveness of suppression by syngeneic antibody.

In the suppression of the growth of a mouse lymphoma 6C3HED by antibody, the effectiveness of antibody in suppressing growing or established tumor cells and comparable number of freshly injected tumor cells is quantitatively similar. The effectiveness of antibody diminishes markedly when the number of tumor cells per mouse reaches the level of 10(6) due to the development of a macrophage shortage. At the 10(5) tumor cells level, antibody-mediated suppression takes place in an optimal manner and between 10(5) and 10(4) tumor cell numbers, the amount of antibody required to suppress 50% of the tumor cells is directly proportional to the number of tumor cells suppressed.

Immunotherapy of cancer with antibody.

A long-term suppression of a transplanted solid tumor that has been growing in a syngeneic animal can be achieved by the administration of antibody against the tumor. The susceptibility of such growing tumor cells to antibody treatment is similar to that of a comparable number of freshly injected tumor cells.

The effects of bretylium on C fibre excitation and noradrenaline release by acetylcholine and electrical stimulation.

1. The effects of bretylium on the excitation of postganglionic adrenergic C fibres by acetylcholine and the release of noradrenaline by acetylcholine and electrical stimulation of the splenic nerves have been studied using the in situ and cross perfused cat spleen.2. Close arterial injections of acetylcholine (10-200 mug) evoked a brisk asynchronous discharge in fine filaments of the splenic nerve which reduced the height of the orthodromic C fibre compound action potential.3. Hexamethonium abolished both the excitation of C fibres and release of noradrenaline by acetylcholine, whereas the liberation of noradrenaline by electrical stimulation of the splenic nerves remained unchanged.4. Bretylium (0.5 and 1.0 mg) given close arterially blocked the output of noradrenaline and contractions of the spleen that occurred in response to nerve stimulation (30 c/s) but had much less effect on the responses to acetylcholine.5. Bretylium (2-4 mg) given close arterially blocked the output of noradrenaline and contractions of the spleen caused by both nerve stimulation (30 c/s) and acetylcholine.6. The close arterial injection of (+)-amphetamine sulphate (100 mug) after bretylium (2-4 mg) partially restored the output of noradrenaline and contractions of the spleen to both nerve stimulation and acetylcholine.7. The difference in the sensitivity to blockade by bretylium of the effects of nerve stimulation and the sympathomimetic effects of acetylcholine did not exist if the more "physiological" frequency of stimulation of 10 c/s was employed.8. The close arterial injection of acetylcholine (100 mug) caused a mean average fibre discharge frequency of 5.4 spikes/sec.9. Bretylium in amounts sufficient to completely block the sympathomimetic effects of acetylcholine did not alter the excitation of C fibres by acetylcholine.10. The significance of these results is discussed both in relation to the mode of action of bretylium and to the use of these differential effects of bretylium as evidence for the "cholinergic link" hypothesis.

A comparsion of the effects of prazosin and hydrallazine on blood pressure, heart rate and plasma renin activity in conscious renal hypertensive dogs.

Prazosin, a novel antihypertensive agent, and hydrallazine have been compared in renal hypertensive dogs. I.v. prazosin (0.1 mg/kg) produced greater falls in blood pressure than hydrallazine (1 mg/kg i.v.) but, in contrast to hydrallazine, did not cause any significant alteration in heart rate or plasma renin activity in these animals. When given orally, prazosin (0.1 mg/kg) produced falls in blood pressure equivalent to those observed with i.v. hydrallazine (1 mg/kg) again without significant tachycardia or plasma renin activation.

Allergic rhinitis: a growing primary care challenge.

PURPOSE: To describe the growing problem of allergic rhinitis (AR) and the latest recommendations on its diagnosis and management for the nurse practitioner (NP) in primary care settings. DATA SOURCES: Recent clinical research, review articles and consensus guidelines, and the author's clinical experience. CONCLUSIONS: The prevalence of AR is increasing, possibly due to increased airborne pollutants, poor ventilation, and rising levels of indoor allergens. Allergic disease is systemic and rarely involves a single symptom. Treatments include reducing exposure to allergens as well as pharmacotherapy. IMPLICATIONS FOR PRACTICE: Patient education is crucial for successful management and includes understanding the allergic basis of symptoms, reducing allergen exposure, understanding proper use of medications, and reassessing the plan on a regular basis.

Antibody-mediated suppression of lymphoma: participation of platelets, lymphocytes, and nonphagocytic macrophages.

Humoral antibody directed against a grafted murine lymphoma can suppress the growth of the tumor in mice of the inbred strain native to the tumor. Antibody, however, cannot suppress the tumor growth in mice given 500 R of whole-body irradiation. When the tumor-antibody inoculum is admixed with lymphocytes or macrophages obtained from peritoneal exudate, macrophages experimentally rendered nonphagocytic, or with platelets isolated from peripheral blood, the tumor growth is suppressed in irradiated mice. These results indicate that mechanisms other than phagocytosis may play an important role in antibody-mediated suppression of tumor growth in vivo.

Facilitators and inhibitors of the emergency nurse practitioner role.

Factors that facilitate or inhibit implementation of the Emergency Nurse Practitioner (ENP) role were studied. ENPs were surveyed by questionnaire. Sixty-eight (64.7 percent) responded, providing data about motivating factors influencing the decision to seek ENP education and subsequent job acceptance; current employment status; role concept; performance and autonomy; and barriers to practice. Nearly all program graduates had practiced as ENPs, but only 43 percent were doing so at the time of survey. Of the rest, a third were nurse practitioners in a nonemergency room setting (NPs), and 22 percent were practicing in other nursing roles (NNPs). Respondents were motivated to enter an ENP program by greater role credibility, autonomy, job advancement, learning new skills, and dissatisfaction with their jobs. Similarly, ENPs accepted their jobs because of the opportunity to use their new skills, available medical backup, and the location of employment. NPs and NNPs reported leaving ENP practice because of resistance from other health care providers. ENPs experienced resistance in their practice, although they believed the role was accepted by consumers and health care colleagues. They tended to perform tasks they believed appropriate to the role and not to perform tasks inappropriate to the role. Most ENPs reported role autonomy and a collaborative or independent practice. While 42 percent reported no barrier to practice, the majority of ENPs reported greater than one barrier. Resistance and legal status were the most frequently reported barriers. The need for further onsite and nationwide research on the ENP is suggested.

Absorption of amlodipine unaffected by food. Solid dose equivalent to solution dose.

The oral bioavailability of amlodipine in healthy volunteers was compared in two separate studies after solution and capsule doses, and after capsule doses in fed and fasting states. The bioavailability of amlodipine was equivalent both in terms of rate and in extent of absorption between solution and capsule doses and in the fed and fasting states.

Seasonal variation in dust mite and grass-pollen allergens in dust from the houses of patients with asthma.

In order to study seasonal variation in dust-mite allergen, we obtained dust samples from bedding, carpet, and/or sofas in 12 houses in central Virginia, monthly, for 1 year. The houses included those of nine patients with asthma of whom six were allergic to dust mites. Dust samples were assayed with an inhibition radioimmunoassay for mite allergen that detects cross-reacting determinants on Der f and Der p I from Dermatophagoides farinae and D. pteronyssinus, respectively. The results are expressed as micrograms of antigen P1 equivalent (AgP1Eq). The results demonstrate that large seasonal variations in allergen, i.e., more than twentyfold, can occur in dust from all sites and are not restricted to the houses of allergic patients. However, dust from some sites, particularly sofas, remained "high" (greater than 10 micrograms AgP1Eq per gram), whereas dust from other sites remained "low" (less than 1 microgram AgP1Eq per gram) throughout the year. Levels of mite allergen generally started to rise in July about 1 month after the rise in humidity. In August to December, the mean levels of AgP1Eq in house dust were highly significantly increased relative to April to May. In keeping with this finding, in 31 of 37 sites, the highest level for the year was observed in August through December. In four sites, mite bodies were counted, and the numbers increased sharply in June to July; however, they decreased in September in parallel with falls in humidity but several months before the fall in mite allergen. Ryegrass-pollen allergen in 12 sites was also assayed in house dust, and pollen-allergen levels demonstrated a sharp increase in May or June that fell back to preseason values within 2 months. Dust was also obtained from the houses of 50 patients with acute or severe asthma. The results on these samples suggest that mite-allergic patients are more likely to have attacks in the fall at a time when their houses have greater than 10 micrograms AgP1Eq per gram of dust. The magnitude of changes observed seasonally within individual houses and of differences between houses within a close geographic area suggests that interpretation of the relationship between allergic symptoms and mite-allergen exposure will require measurement of mite-allergen levels in individual houses.

Chemical treatment of carpets to reduce allergen: comparison of the effects of tannic acid and other treatments on proteins derived from dust mites and cats.

BACKGROUND: Several chemical treatments have been recommended for reducing mite and other allergen levels in carpets, including the protein-denaturing agent tannic acid (TA). OBJECTIVE: We evaluated the efficacy of TA and other treatments on mite and cat allergens in carpets within houses. The effects of TA were assessed on Der p 1 and Der f 1, on group II mite allergens, and on the major cat allergen Fel d 1. METHOD: Carpet treatments tested were benzyl benzoate moist powder, a 3% TA spray, and two carpet cleaners (Host and Capture). Carpets were treated twice and dust samples collected on a biweekly basis for 8 weeks: these samples were extracted in saline solution alone. Additional studies evaluated the effects of TA on 17 carpets. Carpets were treated twice (on days 0 and 28) and samples collected on days 0, 1, 7, 14, 28, and 42. Eighteen carpets were untreated controls. Dust samples were extracted separately in both saline solution and in the presence of 5% bovine serum albumin. RESULTS: Benzyl benzoate and the two carpet cleaners reduced group 1 dust mite allergen concentrations in carpet dust. In addition, benzyl benzoate and TA reduced airborne group 1 mite allergens by more than 64%. Further studies showed that, in keeping with in vitro studies, TA inhibited the assay and bovine serum albumin abrogated this effect. Significant reductions after treatment occurred only for Der f 1 and group 2 dust mite allergens (p = 0.005 and p = 0.035, respectively). However, for all mite allergens the percentage changes after treatment were significant when compared with untreated carpets (p < 0.005 for Der f 1 and group 2 mite, p < 0.02 for Der p 1) but not for cat allergen (p > 0.3). The results suggested that repeated application of TA was necessary to maintain reduced allergen concentrations. CONCLUSION: Carpet treatments can reduce mite-derived allergen levels in airborne and carpet dust. However, the effects do not appear to be maintained for long periods, are not dramatic, and are different for different allergens.

Chemical treatment of carpets to reduce allergen: a detailed study of the effects of tannic acid on indoor allergens.

Tannic acid (TA), a protein-denaturing agent, has been reported to reduce allergen levels in house dust and is marketed for that purpose as 1% and 3% solutions. We investigated the effects of TA on dust allergens by using monoclonal antibody-based ELISAs for mite (Der p I, Der f I, and group II) and cat (Fel d I) allergens. Initial studies confirmed that TA reduced allergen levels in carpet dust. However, when dust samples from treated carpets are extracted in saline solution, residual TA redissolves and may interfere with the assessment of allergens. In the laboratory, concentrations of TA as low as 0.1% inhibited the assays, but this effect may be prevented by addition of 5% bovine serum albumin (BSA). After treatment of dust samples in the laboratory with 3% TA, the apparent reductions in Der p I and Der f I levels were 89% and 96%, respectively, but when the samples were extracted in 5% BSA the reductions were 74% and 92%. Similar effects were seen with dust samples from carpets treated with TA. In an extreme case in which a carpet had been repeatedly treated with TA, the apparent concentration of Der p I was < 0.05 microgram/gm without BSA and 2.1 and 8.4 microgram/gm when extracted in the presence of 1% and 5% BSA, respectively. Our testing of the ability of TA to denature Fel d I demonstrated an 80% reduction in allergen, but only in samples with an initial concentration of less than 200 micrograms Fel d I/gm dust.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of IgE antibody responses by glutathione S-transferase from the German cockroach (Blattella germanica).

We report that a major 23-kDa allergen from German cockroach (Blattella germanica) is a glutathione S-transferase (EC 2.5.1.18; GST). Natural B. germanica GST, purified from cockroach body extracts by glutathione affinity chromatography, and recombinant protein expressed in Escherichia coli using the pET21a vector, showed excellent IgE antibody binding activity. B. germanica GST caused positive immediate skin tests in cockroach-allergic patients using as little as 3 pg of recombinant protein. The NH2-terminal sequence of the natural protein and the deduced amino acid sequence from cDNA were identical except for one substitution (Phe9 --> Cys). Assignment of this protein to the GST superfamily was based on binding to glutathione and sequence identity (42-51%) to the GST-2 subfamily from insects, including Anopheles gambiae and Drosophila melanogaster. B. germanica GST contained 18 of the 26 invariable residues identified in mammalian GST by x-ray crystallography and exhibited enzymic activity against a GST substrate. Our results show that cockroach GST causes IgE antibody responses and is associated with asthma. The data strongly support the view that the immune response to GST plays an important role in allergic diseases.

Dust mite allergen avoidance in the treatment of hospitalized children with asthma.

BACKGROUND: Asthma is a leading cause of hospital admission in children. The majority of children with asthma are sensitized and exposed to inhalant allergens that may contribute to chronic airway inflammation. OBJECTIVE: To evaluate the practicality and effects of dust mite (D. farinae and D. pteronyssinus) allergen avoidance in homes of children hospitalized with acute asthma. METHODS: Children 5 to 18 years of age who were admitted with asthma to a suburban Atlanta hospital were randomly assigned, without knowledge of allergen sensitization or exposure in their houses, to active (n = 13) or placebo (n = 10) treatment group. Active treatment included encasing mattress, box springs, and pillows in allergen impermeable covers; weekly hot water wash of bed linens; replacement of bedroom carpet with polished flooring; and 3% tannic acid spray to living room carpet. Placebo treatment included permeable encasing for bedding, cold water wash, and water spray for carpet. Dust samples were analyzed for dust mite, cockroach, and cat allergens, while serum samples were analyzed for IgE antibodies to the same allergens. Outcome measures included daily peak expiratory flow rates, spirometry, methacholine inhalation challenge, and hospital readmission. RESULTS: Children in both groups were similar by demographics, sensitization, and exposure to dust mite allergen. Allergen levels fell > 3-fold in many active and placebo homes. Children in the active group had improved PEFR at 3 and 6 months after intervention (P < .04, P < .05, respectively). Six of seven children in the study who were sensitized and exposed to dust mite allergen demonstrated improved PEFR at 3 months when allergen levels fell in both bedding and bedroom floor. There was no difference in FEV1 or methacholine challenge, although a few children in either group could tolerate methacholine because of bronchial hyperreactivity. Six children (four active and two placebo) were readmitted to hospital during the study. CONCLUSION: Increases in PEFR were recorded among children in the active treatment group and also among sensitized patients whose dust mite allergens fell. These results support the hypothesis that avoidance can be effective even among children admitted to hospital. The study was complicated by insufficient numbers of mite-allergic children and poor compliance with diaries and the protocol. Recruitment from the hospital resulted in participants with more severe asthma than anticipated. The results also suggest that many of the patients in this group will continue to have exacerbations triggered by upper or lower respiratory tract infections.

Treatment of late-onset asthma with fluconazole.

BACKGROUND: Although the etiology of intrinsic or late-onset asthma is generally not known, some cases are associated with overt dermatophyte infection and immediate hypersensitivity to proteins derived from fungi of the genus Trichophyton. OBJECTIVE: We sought to test the efficacy of oral antifungal treatment for Trichophyton-induced asthma by using fluconazole in a placebo-controlled trial. METHODS: Eleven patients with severe or moderately severe asthma were randomized to treatment with fluconazole 100 mg daily or placebo for 5 months (phase 1); during the following 5 months, all patients received active drug (phase 2). Subjects were evaluated by skin tests, bronchial provocation tests, and measurement of serum antibodies to Trichophyton species antigens. Clinical response was monitored by changes in peak flow values measured during a 2-week period at the end of each phase and by changes in bronchial sensitivity, symptoms, and steroid requirements. RESULTS: At the end of the first 5 months of active treatment, there was a highly significant decrease in bronchial sensitivity to Trichophyton (P =.012) and in oral steroid requirement (P =.01). At the end of phase 2, mean peak expiratory flow rates increased in 9 of 11 patients. An improvement in symptoms, peak flow, and steroid use was maintained up to 36 months after starting fluconazole in patients who continued to receive treatment. CONCLUSION: The results show that fluconazole can be useful in the treatment of patients with severe or moderately severe asthma who have dermatophytosis. These findings are consistent with the argument that proteins derived from fungi on the skin and nails can contribute to allergic disease.

Definition of a Trichophyton protein associated with delayed hypersensitivity in humans. Evidence for immediate (IgE and IgG4) and delayed hypersensitivity to a single protein.

Dermatophytes of the genus Trichophyton cause infections of human skin, nails, and hair. Unlike most Ags, Trichophyton can elicit either immediate (IH) or delayed (DH) hypersensitivity skin reactions. Previous studies isolated a 30-kDa Ag (Tri t 1) that caused IH skin tests. The study presented here used skin testing and in vitro T cell proliferation assays to monitor purification of an Ag, designated Protein IV, associated with DH reactions. Protein IV was purified by cation exchange HPLC; amino acid sequence analysis of the N-terminus and nine internal peptides (143 residues) revealed no homologies to Tri t 1 or to any other known proteins. A mAb-based ELISA was developed to measure Protein IV. Protein IV elicited DH skin reactions in subjects with a history of athlete's foot but also caused IH skin reactions. Serologic responses to Protein IV were studied in 59 adults who had been skin tested with Trichophyton extract. IH skin reactions were associated with a positive RAST (14/23) as well as with specific IgE (13/23) and IgG4 (14/23) Abs to Protein IV. DH skin tests were not associated with IgE or IgG4 Abs. IgE anti-Protein IV Abs were quantitatively correlated with IgG4 Abs (r = 0.57, p < 0.001). Specific IgG Abs to Protein IV were highest in IH subjects (gm = 230 U/ml), and lowest in those with DH (gm = 91 U/ml) or negative (gm = 81 U/ml) skin tests; furthermore, the prevalence of IgG Abs increased significantly with age. Protein IV is the first defined protein associated with both DH and IH skin reactions; these reactions are characterized by distinct serologic responses. The results establish that diverse immune responses in humans can be directed against the same protein.