The cholinergic nervous system and immediate hypersensitivity: I. Eccrine sweat responses in allergic patients

The cholinergically innervated human eccrine sweat gland is a readily available organ permitting the assessment in allergic patients of cholinergic reactivity with few or no adrenergic influences. The sweat responses of four matched groups (male allergic, female allergic, male control, and female control) to intradermal Mecholyl from 0.1 μg to 100 μg was compared; the 45 male and 45 female allergic patients demonstrated statistically significant increases in sweat responses to essentially all concentrations of Mecholyl examined. No difference in the sweat responses of patients with allergic rhinitis alone as compared with patients with both allergic rhinitis and allergic asthma was noted. Five patients with intrinsic asthma most closely resembled the allergic groups in their responses and 8 patients with vasomotor rhinitis sweated at or below the control groups. The increased sensitivity of allergic patients to cholinergic stimulation as measured by eccrine sweat responses suggests that this hyperresponsiveness may be one of the underlying defects in allergic disease.     

Quantitative assays of pharmacologic aerosols used in studying asthma

To more nearly accurately quantitate the dose of pharmacologic agents delivered to human and animal airways via aerosols, we have developed a monodisperse aerosol containing either methacholine or histamine that permits a light scattering device (tyndallometry) to measure accurately the quantity of inspired and expired particles. These aerosols (described in previous studies) are simultaneously tagged with a radioactive label (technetium 99m) to permit the use of external gamma camera imaging. Present work focuses on the development of assay techniques to measure the quantity of methacholine delivered in these aerosols. The lack of specific radioimmune or radioenzyme assays coupled with the cross-reaction of organic contaminants with conventional chemical reagents for measuring methacholine required the development of separative techniques to isolate the methacholine from the organic aerosol contaminants. With aqueous extraction and column separation we have been able to completely isolate the methacholine from these contaminants. This allows the application of standard spectrophotometric assays for methacholine to quantitate the methacholine in the resulting solution. These separative techniques will permit the use of these aerosols in quantitative studies of airway reactivity.     

Hysterectomy in six European countries

Gynaecologists have been criticized in recent years because of their attitude towards hysterectomy; it is often stated that they are too ready to consider hysterectomy to be indicated and that hysterectomies are carried out too frequently.In order to obtain insight into the incidence of hysterectomy, 2066 women between 40 and 70 yr of age, composing a sample covering 6 European countries, were asked whether they had undergone this operation. Of the total sample, 11.4% had been hysterectomized, the highest percentage being found in Italy (15.5%) and the lowest in France (8.5%).The most important factor that influenced the relative frequency of hysterectomy was age: the percentage of women who had undergone hysterectomy increased with age up to 55–59 yr, but fell thereafter. Another significant factor was civil status; there were fewer divorcees or widows at the moment of operation than married or never-married women.The relationship between the incidence of hysterectomy and age is a parabolic one. To explain this curve the authors postulate that two trends must have played a rôle: firstly; a greater need for hysterectomy with increasing age and, secondly a decrease in the reluctance of the gynaecological profession to perform a hysterectomy and/or of women to undergo this operation.Statistical analysis confirms the existence of this second trend over the period 1960–1975. The chances of a young woman losing her uterus before her 70th year went up linearly to 19.8% in 1975. By extrapolation a figure of 21% is obtained for 1980. Satisfaction with the result of the operation was lowest in Italy and Germany; satisfaction was also lowest in rural areas.     

The relative merits of cromolyn sodium and high-dose theophylline therapy in childhood asthma

The use of cromolyn sodium (SCG) and high-dose theophylline (HDT) in the treatment of chronic perennial asthma in children is reviewed. It is noted that the regimens are only suitable for children with persistent symptoms uncontrolled by simpler forms of treatment. The methods of administration and dosage based on pharmacologic data are considered, and the potential importance of long-acting theophylline and nebulized cromolyn preparations is noted. Short-term studies have confirmed the efficacy of both drugs, and a comparative study showed little difference between them. Long-term studies of SCG have demonstrated its value to some 66% of children without serious side effects. No formal long-term studies have been carried out on HDT. Side effects from theophylline can often be eliminated by careful control of blood levels. From published evidence, neither SCG nor HDT is effective in steroid-dependent asthmatic children, and they contribute little, if anything, to management in such cases. The difference in cost of the drugs is small when all factors are considered, and either regimen is justified by the saving in medical expenses when used for carefully selected patients.     

Magnetophosphenes: a quantitative analysis of thresholds

Low-frequency and transient magnetic fields of moderate flux densities are known to generate visual phenomena, so-called magnetophosphenes. In the present study, time-variable very low frequency (10–50 Hz) electromagnetic fields of moderate flux density (0–40 mT) were used to induce magnetophosphenes. The threshold values for these phosphenes were determined as a function of the frequency of the magnetic field both in normal subjects and colour defective ones. Maximum sensitivity occurred at a frequency of approximately 20–30 Hz, and with broad-spectrum light the threshold flux density was 10–12 mT. The threshola values were found to be dependent upon the intensity and the spectral distribution of the background light. Sensitivity decreased during dark adaptation. In certain respects deutans differed from subjects with normal colour vision. Possible mechanisms for generation of magnetophosphenes are discussed. The present magnetic threshold curves show a close resemblance to corresponding curves obtained by electric stimulation at various frequencies provided the electric thresholds are divided by the a.c. frequency. These problems are under current investigation in our laboratory. This is in full agreement with the assumption that the fluctuating magnetic field affects retinal neurons by inducing currents which polarise synaptic terminals.     

Skin tests and blood leukocyte histamine release of patients with allergies to laboratory animals

Skin tests and in vitro histamine-release reactions were used to evaluate 130 patients observed in an employee allergy clinic at a biomedical research facility. The allergens used included extracts from pollens (ragweed, grasses, trees, weeds), molds, mixed feathers, house dust, cat, dog, mouse, rat, rabbit, guinea pig, and hamster. Of all patients, 66% complained of allergic symptoms on laboratory animal exposure, although only 52% worked directly with animals. Among patients with symptoms, 91% were positive by skin test to at least one laboratory animal, and 46% had asthma. The median length of exposure to laboratory animals before onset of symptoms was 2.8 yr with 60% of the patients developing their symptoms within 3 yr. Among patients who had allergic symptoms before exposure to laboratory animals, 79% were skin test positive to laboratory animals when they were evaluated in this study. There was a close association found between the skin test and histamine-release results with the laboratory animal allergens: 91% of the 4+ skin reactors had leukocytes positive for histamine release versus 5% of the leukocyte donors with less than 1+ skin reactions. A close relationship in positive reactions to different laboratory animal allergens was also found. For example, individuals positive to mouse were positive also to rat (95%), rabbit (79%), guinea pig (83%), and hamster (88%). Patients who reacted to laboratory animals also reacted to some extent to house dust and cat and dog allergens, and about one half of the animal-allergic individuals reacted to pollens. Although nonpollen-allergic individuals can develop sensitivity to laboratory animals, the group at higher risk are allergic individuals, especially those sensitive to house dust, cats, or dogs.     

Conversion of nonfusing mumps virus infections to fusing infections by selective proteolysis of the HN glycoprotein

Mumps virus strains differ in their ability to induce cell fusion following an infection: strains with activeneuraminidase (NANase) fail to cause cell fusion, while strains with less active NANases cause cell fusion. When chymotrypsin is added to infected cells, cell fusion is amplified in a concentration-dependent manner for all mumps virus strains. Virions produced in such infections do not express HN glycoprotein-associated activities. Chymotrypsin treatment of purified mumps virus in vitro results in sequential cleavage into two glycopolypeptides, HNc1 (32K) and HNc2′ (41K), with concomitant loss of hemagglutinating and NANase activities, and infectivity. Further incubation with chymotrypsin causes complete degradation of HNc1 and digestion of HNc2′ to HNc2 (13K–19K). Both HNc2′ and HNc2 contain the [³H]palmitic acid label found in the HN polypeptide, which suggests that these fragments are associated with the viral membrane. Analyses of infected cells and released virions indicate that chymotrypsin acts similarly on HN exposed at the cell surface. Exogenous NAnase does not abolish the protease-augmented cell fusion though it does reduce cell fusion of untreated fusing strain infections. These results confirm that mumps virus HN glycoprotein is critically linked to cell fusion cytopathology and show that cyrptic cell fusion activity in nonfusing strain infections can be unmasked by the proteolytic removal of the HN glycoprotein.     

Different specificities of an HLA-DRw6 haplotype detected by alloreactive T lymphocytes

DRw6 has been difficult to define serologically. In the present experiments we have developed T cell lines in order to characterize the components of a DRw6 haplotype. This was accomplished by priming T cells with allogeneic mononuclear cells mismatched for DRw6, Dw6, and MT2. Subsequently, three sublines with distinct reactivity patterns were derived by limiting dilution. The specificities detected by these sublines included: (a) a specificity found on a subset of cells positive for DRw6 which was inhibited by monoclonal antibodies against DS(DC), the human homologue of the murine IA-encoded molecules, (b) another DRw6-associated specificity blocked by an MT2-like antibody, and (c) an MT2-like specificity blocked by monoclonal antibodies reactive with a different MT2-associated determinant. These results show that more than one IE-like, as well as the DS/DC (IA-like) molecules, carry distinctive antigenic epitopes that can be recognized by allogeneic T cells. Primed T cell lines may be useful for a better definition of certain haplotypes which are at present difficult to characterize with serological reagents alone.     

Analysis of the renal tissue of a woman chronically exposed to cadmium

Summary In a 61-year-old woman, who had been exposed for 20 years to cadmium in the production of Ni-Cd batteries, nephrectomy of the contracted kidney was performed. The removed kidney was examined histologically and the cadmium concentration was determined in the cortex (44.97 g g^–1) and in the medulla (7.71 g g^–1). The homogenates of the renal cortex and medulla were subjected to gel filtration on Sephadex G-75. In the cortex, as well as the medulla, cadmium was predominantly found in the low-molecular (metallothionein) fraction, but in the cortex, Cd content in this fraction was six times higher than in the medulla. The determination of SH groups and proteins in high- and low-molecular fractions indicates an induction of the metallothionein formation primarily in the renal cortex.