Lymphocyte responses to purified ragweed allergens in vitro: I. Proliferative responses in normal,newborn, agammaglobulinemic,and atopic subjects

To evaluate cell-mediated immune responsiveness to pollen allergens in atopic subjects, we studied the deoxyribonucleic acid (DNA) synthetic responses of their cultured lymphocytes to purified ragweed antigens E, K, and Ra-3. Since lymphocytes from some highly ragweed-sensitive subjects gave poor proliferative responses when harvested on day 6, we undertook a series of dose-response and time-course studies in atopic and control subjects. Surprisingly, vigorous DNA synthetic responses to antigen E occurred with lymphocytes from all 45 subjects, including 19 highly ragweed-sensitive atopic adults (8 immunotherapy treated, 11 untreated); 13 nonatopic controls; 4 newborns, and 9 agammaglobulinemic patients. The geometric mean of peak response counts per minute in all 45 subjects was 21,163 and in unstimulated cultures was 2,416 (p = < 0.0001). The mean day on which the maximal responses occurred was 8.7, and the mean dose eliciting the maximum responses was 59 μ/ml. Statistical comparisons of the stimulated culture data revealed no significant intergroup differences. The finding of vigorous responsiveness to these purified pollen allergens by lymphocytes from nonatopic normal, newborn, and agammaglobulinemic subjects suggests that ragweed pollen antigens are either ubiquitous and lead to cell-mediated responsiveness in all subjects with intact cell-mediated inmunity, or that they may have mitogenic properties in addition to their known antigenic properties.     

Depression of cell-mediated immunity in atopic eczema

Prompted by recent observations that the thymus exerts an important regulatory influence over IgE antibody production in lower species, we conducted studies of immune function in 21 patients with atopic eczema to seek evidence for a similar relation in man. Skin tests for delayed hypersensitivity to Candida albicans and streptokinase-streptodornase (SK-SD) revealed a striking degree of anergy that correlated with the severity of the eczema. A correlation was also noted between the extent of the dermatitis and the magnitude of the serum IgE concentration. Other immunologic abnormalities did not appear related to the severity of eczema but pertained to the group as a whole. These included significantly (p = < 0.0001) lower mean percentages of spontaneous sheep erythrocyte (E) or T cell rosettes and of rosettes with neuraminidase-treated sheep erythrocyte (E_n) rosettes, and significantly lower in vitro lymphocyte responsiveness to the mitogens concanavalin A (p = 0.0013) and pokeweed mitogen (p = 0.0002) and to Candida antigen (p = 0.0017) than in normal subjects. Responses to phytohemagglutinin and tetanus toxoid were also depressed but differences were not statistically significant. An increased percentage (p = 0.0324) of peripheral blood B lymphocytes bearing the complement receptor was noted, but, except for a slight increase in lymphocytes bearing IgD, percentages of lymphocytes bearing other immunoglobulins (including IgE) were not elevated.     

Abnormalities of leukotaxis in atopic dermatitis

Leukocyte chemotaxis studies were performed in 14 patients with atopic dermatitis. Monocyte chemotactic responsiveness (MCR), polymorphonuclear leukocyte (PMN) chemotactic responsiveness (PCR), and patient serum inhibition of normal monocyte chemotaxis were evaluated. The most common defect noted was depressed MCR. This was found in 8 of the 14 patients and was associated with a chemotactic inhibitor in the serum of 5 of 6 of the 8 with depressed MCR whose sera were so tested. Depressed PCR was found in 3 of 10 patients studied. Ten of the 14 patients had depressed chemotaxis of at least one cell type. Depressed chemotaxis was not related to the presence of infection, to the serum IgE level, or to the severity of the eczema, and it could not be produced in vitro by incubating normal cells with histamine or IgE myeloma. These studies demonstrate a high frequency of leukocyte chemotactic abnormalities in patients with severe atopic dermatitis. Elucidation of the clinical significance of the leukotactic abnormalities observed and determination of whether they are basic or secondary to the disease process must await further study.     

Population differences in cutaneous methacholine reactivity and circulating IgE concentrations

We evaluated the incidence of allergic and vasomotor symptoms, serum IgE concentrations, and the cutaneous responses to allergens and/or methacholine in 229 Waorani Indians residing at 300 m altitude near the headwaters of the Amazon River, 39 Tibetans residing at 4000 m in the Himalayas, and 84 healthy subjects residing at 150 m in the piedmont region of North Carolina. The Waorani Indians had a high level of intestinal parasitism, an intermediate level of parasitism occurs in Tibetans, and parasitism is rare in the control population. One Waorani Indian (less than 1%), six Tibetans (15%), and 59 North Carolina subjects (88%) had a past history of allergic or vasomotor symptoms. The prevalence of positive epicutaneous allergen skin tests among the Waorani was 40 in 2910 tests and was significantly less (chi-squared = 184.5; p less than or equal to 0.0001) than the 151 in 1344 incidence in the North Carolina subjects. Large highly significant differences (p less than or equal to 0.0001) were detected between the geometric mean IgE concentrations (international unit per milliliter) and methacholine-induced cutaneous flare responsiveness (millimeter) elicited, respectively, in comparisons between the Waorani Indians (9806 IU/ml; less than 1.0 mm), Tibetans (2930 IU/ml; 2.06 mm), and North Carolina subjects (108 IU/ml; 4.49 mm). Differences in methacholine sensitivity were small and not significant. A highly significant inverse relationship (r = -0.50, p less than or equal to 0.0001) was detected between the circulating IgE concentrations and the methacholine-induced cutaneous flare responsiveness in this cross-cultural, cross-environmental comparison of three populations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does hyperimmunoglobulinemia-E protect tropical populations from allergic disease?

The Waorani Indians of eastern Ecuador have the highest blood concentration of IgE reported in a human population. Evidence obtained by medical history, physical examination, and immediate hypersensitivity skin tests suggests that pollen allergy and other atopic diseases are rare among the Waorani. A similar association between parasite-induced hyperimmunoglobulinemia-E and a low prevalence of conventional atopic disease has been reported in numerous other tropical populations. Saturation of mast cell IgE receptors with antibodies directed to the parasite and/or other antigens and competitive inhibition of passive binding of pollen allergen-specific IgE is one hypothetical cause of this association. We have tested this interesting conjecture by passively sensitizing the skin of Waorani Indians with serum containing pollen allergen-specific IgE antibodies. Waorani Indians with hyperimmunoglobulinemia-E can be adoptively sensitized with human ragweed or rye grass hyperimmune IgE antisera. This suggests that the cutaneous mast cells of healthy Waorani have active IgE receptors. The high circulating plasma concentrations of IgE in the Waorani do not prevent adoptive cutaneous sensitization with pollen-specific IgE antibodies.     

Atypical facial pain and trigeminal neuralgia: a comparison study

Review of the charts of 43 patients with atypical facial pain and 44 with trigeminal neuralgia indicates that the two pain syndromes can be discriminated only on the basis of the patient's age at the time of pain onset and history of concomitant psychiatric illness and psychiatric corisultation. The results mdicate the need for a thorough collection of psychosocial data on the part of clinicians working with these patients.     

Chronic low back pain and depression

In an attempt to clarify the relationship between chronic low back pain and depression, the authors studied the incidence of depression, alcoholism, and chronic back pain in first-degree relatives of chronic pain patients with and without depression. A higher incidence of recurrent unipolar depression was found in those relatives of patients with depression than without depression. These findings raise questions about the concept of chronic low back pain simply as a variant of depression and they suggest that the occurrence of major depression together with chronic back pain might relate to genetic vulnerability to depression.     

The medical-psychiatric unit and psychosocial education of internists

A milieu for teaching internal medicine residents the psychosocial aspects of caring for patient son a medical psychiatric unit is described. The teaching portion of this program is characterized by structured goals. Testing of the residents before and after the rotation disclosed a highly significant (P = .01) improvement in their knowledge. Directions for further evaluation are presented.     

Pseudoseizures: Recognition and treatment

Pseudoseizures involve a subjective loss of consciousness, usually resulting from a psychological disturbance. Drug intoxication, panic or anxiety attacks, or hypoglycemia may also induce behavior that resembles epilèptic manifestations. Multiple EEG evaluations and careful clinical observation can rule out epilepsy. Psychiatric treatment, including family interviews and sympathetic discussion of the underlying emotional problem with the patient, should be provided when appropriate.     

The differential diagnosis of catatonic states

Catatonic states do not always signify schizophrenia. Catalepsy, mutism, stereotypy, muscular rigidity, and other signs of catatonia may reflect drug overdose, an acute delirium, or the subacute stage of viral encephalitis. The misdiagnosis of an underlying medical condition as a psychiatric disorder can have fatal results. A mental status examination, a thorough neurologic evaluation, and appropriate laboratory and cerebrospinal fluid tests may be necessary to identify the cause of the catatonic condition.     

Psychiatric education of the internist: A teaching conference approach

Communication with the nonpsychiatric physician is of major concern to the consultation-liaison psychiatrist. Fundamental differences in the language, literature, and teaching methods of psychiatrists and of nonpsychiatric physicians frequently impede effective collaboration and, more important, interfere with excellent patient care. With this difficulty in mind, the authors redesigned a pre-existing “patient care conference” to more closely follow the format of a traditional medical teaching conference. This article discusses the new format and the problems it has uncovered, and describes references that have proven useful in the program.     

A serially transplantable human giant cell glioblastoma that maintains a near-haploid stem line

We have karyotyped a human giant cell glioblastoma removed from an 11-year-old girl and have established from it a subcutaneously transplantable line in athymic nude mice. The original tumor contained near-haploid cells with 25 or 26 chromosomes, including two copies of #1, (7 or 7p+) and #18. There were also hyperdiploid (49-52) cells that were tetraploid for these same three chromosome types; doubled versions of the hyperdiploid population were also seen. The stemline of the mouse-grown tumor was 26,X, +1, +7p+, +18 in the first passage and has remained consistently near-haploid through ten serial in vivo passages. Growth stabilization has occurred with an average latency of less than 3 months. This transplantable line is available for evaluating chemotherapeutic responsiveness of human giant cell glioblastoma and for studying near-haploidy in solid human tumors.     

Lung cancer heterogeneity: a blinded and randomized study of 100 consecutive cases

The heterogeneity of lung carcinomas was recognized in the past, but few previous studies attempted to quantitate this heterogeneity. In the present study 100 consecutive cases of lung carcinoma (65 surgical resections and 35 autopsies) were collected, and either the entire tumor or ten blocks were examined in a blinded and randomized fashion using the revised (1981) WHO classification. At least three of five panelists agreed on the major histologic type present for 94 per cent of the slides. Agreement for the diagnosis of small cell carcinomas (at least four of five observers) was 98 per cent, but only 72 per cent agreement was attained for the subtyping of small cell carcinomas (e.g., oat cell versus intermediate). Only 34 per cent of the cases were homogeneous according to the majority of the panelists. An additional 21 per cent of the cases showed minor (subtype) heterogeneity (e.g., mixtures of acinar and papillary patterns in adenocarcinoma). Forty-five per cent of the cases showed major heterogeneity, i.e., at least one slide from the case showed a major histologic type different from that of the remainder. Seven small cell carcinomas were homogeneous, whereas in eight cases mixtures of small cell and other cell types were seen. In all but one of the cases involving bronchioloalveolar cell patterns, other patterns of adenocarcinoma were present elsewhere in the tumor. In all six cases involving giant cell carcinoma patterns, adenocarcinoma patterns were also present in some sections. Heterogeneity was identified by extensive sampling of the entire tumor and was seldom recognized in biopsy specimens.     

Crystalline foreign particulate material in hernia sacs

The subserosal stroma of hernia sacs consistently contains birefringent particulate material, in amounts greater than those observed in other intra-abdominal organs. The major component of this material was shown in the present study to be talc; thus, it cannot be of endogenous origin. Cellular response to this foreign material is remarkably slight. Possible sources of the material and mechanisms of access to the hernia sac were examined in a search of the available literature. It is proposed that the probable source is ingestion with food or, more likely, medications and that the particles reach the peritoneal cavity by migration through the intact intestinal wall. They probably reach the hernia by sedimentation in peritoneal fluid and subsequently migrate into the subserosa. The virtual absence of response to the particles is attributed to their composition (silicate) and their relatively small size (up to about 10 microns) compared with the particles in talc granulomas (up to at least 50 microns).     

Segregation of three recently identified HLA specificities in an American Black family

Three recently identified HLA specificities have been detected in a ten-member American Black family using 8th International Histocompatibility Testing Workshop and local antisera. Independent segregation of the two principal components of 8w59 (Bu and SV) was demonstrated. An Aw19-related specificity also segregated in the family.     

Chromosomal composition of four permanent cultured cell lines derived from human gliomas

Four permanent cell lines derived from malignant human gliomas were karyotyped using Giemsa-trypsin banding. D-65 MG had a stemline with 44 chromosomes, including 11 markers: 1p+, 2q-, 3p-, 3q+, 4p-, 9q-, 11q+, 15q-, 17p+, 21p+, 22q-. The net effect after accounting for fragments in markers was: +8, -10, -16 -X. D-32 MG had chromosome counts 90-91 without a distinct stem karyotype. Modal cells contained from 3 to 5 copies of the normal autosomes and 5 markers: 1q-, 3q-, 7q-, 13q-, 18q-. D-32 MGCl2 had a complex karyotype containing 78-82 chromosomes. There was no stemline, and modal cells varied from one another primarily in their set of marker chromosomes. A total of 23 markers were seen in this line, 17 of which were present in most modal cells. They were partially characterized as: 1q+, 1q+, 2q-, 5q+, 7p-, 7q-, 8p+, 8p+, 9p+, 12p+, 14q-, 16q+, 19q+, 19q+, a small submetacentric chromosome of undetermined origin and two small isochromosomes, i(Dp or Gp) and i(17p or 18p). A-172 MG had a modal peak of 77 chromosomes within which no two cells were exactly alike. Ten markers seen in modal cells were: 1p-, 4p+, 6p+, 6p+, 6q-, 7p-, 9p-q+, 13q+ 14p+, 22q+. There were no normal copies of chromosomes #1, #6, #9, #14. These four glioma-derived cell lines possess unique karyotypes, but each displays some combination of the numerical and structural deviations generally associated with established glioma lines.