Response Of Normal Individuals Research Articles

Polypeptide-specific antibody response to human cytomegalovirus after infection in bone marrow transplant recipients.

Human cytomegalovirus (HCMV) infection continues to be the most important infection occurring after allogeneic bone marrow transplantation (BMT). Although T cell-specific antiviral immunity appears to be necessary for control of the infection, the humoral immune reaction also contributes to a complete immune response. In this paper we report our findings concerning the antibody response to the individual polypeptides of HCMV in patients who had undergone BMT and subsequently had displayed evidence of HCMV infection. Sera obtained from the subjects during and after HCMV viremia were studied by using both a radioimmunoprecipitation assay and an immunoblot assay, and the results were compared with the pattern of antibody response in normal individuals. The results show that the BMT patient can make antibodies to individual proteins of HCMV in a pattern similar to that displayed by persons with natural infection. The polypeptide-specific antibody response present most frequently was directed to proteins of 64 kDa, 50 kDa, and 36 kDa. Some BMT recipients also produced antibody to a wide range of HCMV proteins: 183 kDa, 155 kDa, 130 kDa, 110 kDa, 92 kDa, 86 kDa, 74 kDa, 71 kDa, 69 kDa, 39-44 kDa, 33 kDa, and 29 kDa.

Suppression of a pokeweed mitogen-stimulated plaque-forming cell response by a human B lymphocyte-derived aggregated IgG-stimulated suppressor factor: suppressive B cell factor (SBF).

The mechanisms whereby formed immune complexes (IC) or immunoglobulin aggregates can suppress further antibody production were explored by culturing normal human peripheral blood mononuclear leukocytes (PBL) with heat-aggregated IgG (HAIgG) and collecting the culture supernatants at 24 hr. These supernatants were found to suppress a pokeweed mitogen (PWM)-induced rheumatoid factor plaque-forming cell (RF-PFC) response in normal individuals. PWM-induced anti-trinitrophenylated sheep red blood cell (TNP-SRBC) PFC were also inhibited by suppressor supernatants from HAIgG-stimulated PBL, suggesting that the polyclonal PFC response was inhibited by a suppressor factor. The suppressor factor inhibited PWM stimulated RF-PFC throughout the culture period, but suppression was maximal at the peak of the RF-PFC response. Suppressor factor was only effective at the initiation of cultures, suggesting that it inhibited early events in the PWM-stimulated RF-PFC response. Molecular weight determination of the suppressor factor by differential membrane fractionation suggested a m.w. range of 30,000 to 50,000, and chromatography on Sephadex G-100 showed a peak activity at an approximate m.w. of 32,000. Studies suggested the factor was not an interferon. Depletion of T lymphocytes by E rosetting and macrophages/monocytes by G-10 adherence did not affect the generation of suppressor factor. Depletion of T lymphocytes (OKT4, OKT8) and NK cells (Leu-11b) by antibody-dependent, complement-mediated cytotoxicity also did not affect the generation of suppressor factor. Depletion of B lymphocytes with OKB7 resulted in the generation of significantly less suppressor factor. Suppression produced by unstimulated purified B lymphocytes was approximately one-half that seen when B lymphocytes were stimulated with HAIgG. Differential membrane fractionation studies suggested that only HAIgG-stimulated B cell cultures contained peak activity in the 30,000 to 50,000 m.w. fraction. Supernatants from unstimulated purified T cells also generated suppression, which was approximately one-half of that seen with HAIgG-stimulated B cells, but no increase in suppressor activity was seen in T cell cultures after incubation with HAIgG. These studies demonstrate that HAIgG is capable of stimulating B lymphocytes to produce a lymphokine, suppressive B cell factor (SBF), which is capable of suppressing a polyclonal PFC response. SBF may be important in feedback control of human immunoglobulin production.

Influence of Alexithymic Characteristics on Physiological and Subjective Stress Responses in Normal Individuals

Individual differences in response to stress have been linked to the development of stress-related disorders through the presence of a dissociation between physiological and subjective stress responses. It has been suggested that the presence of alexithymic characteristics may constitute a new source of individual response differences and thereby contribute to the development of a stress-related disorder. However, it is also possible that the presence of alexithymic characteristics is simply a new name for a preexisting construct. The present study examined subjective and physiological stress response patterns in normal individuals with high or low presence of alexithymic characteristics, and the relationship between alexithymia and potentially equivalent constructs. The results revealed that the presence of alexithymic characteristics is independent of repression, trait anxiety, and social desirability. As well, high alexithymics appear to manifest high levels of sympathetic activity, and a dissociation between subjective and physiological stress responses. These results are discussed in terms of the potential contribution of alexithymic characteristics to the development of stress-related disorders.

Neurophysiological and psychological disorders and occupational exposure to organic solvents

A number of reports, particularly from Scandinavian countries, claim that painters and workers in other trades in which prolonged occupational exposure to organic solvents may occur develop a type of mental illness characterized principally by impairment of memory and co-ordination and some deterioration of personality. The condition, called ‘organic solvent disease’, is recognized as a cause of premature retirement and is classed as an occupational disease in certain countries. The conclusions of these reports have been contested and the existence of such a disease entity has been questioned. The publications reporting adverse neurological, neurophysiological and psychological disorders in solvent-exposed workers, and the methods used to determine adverse effects, have therefore been evaluated. In addition, data from animal behavioural studies have been examined but were found to have little or no relevance to the reported human disease. The human data indicate that, of the solvents studied, only CS 2 provided clear evidence of neurotoxic damage detectable by clinical and pathological examination as well as by neurophysiological measurements (e.g. nerve conduction velocity and nerve action potentials) or neuropsychological techniques (e.g. Rorschach inkblot test and WAIS intelligence tests). In the case of several other solvents and mixtures of solvents commonly used in industry, the evidence of CNS impairment, based principally on the response to questionnaries and the results of neuropsychological and neurophysiological examinations was questionable. A critical evaluation of the reliability of these methods in detecting minor deviations from normal and of their ability to provide acceptable evidence of CNS dysfunction or damage leaves little doubt that these methods are of value in investigating personality, intelligence and memory in the clinical examination of individual patients. However, evidence indicates that they are not suitable for use in epidemiological studies, principally because the variability of response in normal individuals is ill-defined and insufficiently investigated. The same conclusion was arrived at in evaluating the contribution of electroencephalography, computerized axial tomography scanning and other electrophysiological examinations to the diagnosis of brain changes in groups of solvent-exposed and unexposed workers. Furthermore, the personality changes identified (by neuropsychological tests) in painters and other workers exposed to solvents could well be produced by ageing, exposure to lead or mercury, excessive alcohol intake, psychoactive drugs or the ordinary stresses of everyday life. These ‘confounding’ factors were rarely taken into account in the studies on which the existence of ‘organic solvent disease’ was founded. The evidence reviewed thus fails to confirm that long-term industrial exposure to solvents (with the exception of CS 2) leads to chronic organic or functional damage of the nervous system in man. However, because data do not entirely refute this view, the controversy is likely to remain until well-designed studies have been performed. Before these are contemplated, the methods for examining minor functional changes in the CNS need to be more fully understood and further developed to make them suitable for use in epidemiological investigations.

Skin window immune response to normal human IgG in patients with rheumatoid arthritis and acute poststreptococcal glomerulonephritis.

The skin window technic was utilized to determine the reactivity of patients with rheumatoid arthritis (RA) and acute poststreptococcal glomerulonephritis (APSGN) to human IgG (H-IgG). The response to H-IgG was compared in nine patients with RA, 20 patients with APSGN, and 10 normal individuals. All subjects were tested concomitantly with the saline solution used as solvent for H-IgG. The normal controls and five patients were challenged, in addition, with diphtheria-tetanus-pertussis antigen (DPT) to which they had previous prophylactic exposure. The following results were obtained: 1) Four patients with RA and nine patients with APSGN responded with increased lymphocyte migration (more than 2 SD above the normal mean level) at nine and 12 hours. 2) The mean estimated immunogenic lymphocytosis (calculated subtracting the lymphocyte counts of the saline skin windows) of both patient groups was significantly higher than that of controls at the same time intervals. 3) The response of normal individuals and patients to DPT was comparable in time of appearance and intensity to the response of patients to H-IgG. Our studies that patients with RA and APSGN respond to H-IgG in a manner comparable to that observed with a known antigenic stimulus and support a clinical role for antiglobulin reactivity.

A satisfactory quantitative test of lymphocyte response to phytohaemagglutinin for the definition of normal control values and recognition of immunological defects.

Despite widespread doubts about the quantitative validity or clinical usefulness of lymphocyte response to phytohaemagglutinin (PHA), a satisfactory quantitative test of such responsiveness suitable for the clinical recognition of immunological defects has been developed here. This was achieved by exploring and controlling technical and other variables in the culture of lymphocytes and the quantitation of their response to phytohaemagglutinin. The aspects evaluated included intraperson as well as person-to-person variations, non-lymphocytic cell content, lymphocyte number, PHA batch, atmospheric conditions, culture duration, and quantitation of response. As a result of the information gained from these studies, together with the normal dose-response curve previously established (Fitzgerald, 1971), a satisfactory quantitative and reproducible method suitable for routine clinical use has been realized. This has been applied to the investigation of patients with suspected immunological deficiency disorders, and significant deviations from the normal have been shown. In addition, a PHA dose-response ratio derived from the responses of normal individuals and patients gives a practical quantitative expression of such defects.

Anatomic localization of the response to ultraviolet radiation in human skin.

In an attempt to elucidate the site of injury from ultraviolet radiation (UVR) in human skin, histologic evaluation was performed after irradiation with the various ranges in the UV spectrum. Response to UVA (320–400 nm) irradiation produced changes varying from predominantly dermal (normal) to showing significant epidermal participation (abnormal). UVB (290–320 nm) irradiation produced both dermal and epidermal alterations, developing a moderate perivascular response in normal individuals and increasing to an intense vasculitis with marked epidermal changes in subjects with light associated diseases. UVC (200–290 nm) irradiation induced intense epidermal reactions and only a mild perivascular response. The common denominator in all instances is the apparent vascular injury.

Physiological response to visual sexual stimuli∗

The effect that environmental stimuli will have on behavior is ordinarily a function of three properties of the stimuli: intensity, meaningfullness and variation (Fiske and Maddi, 1961). Research on physiological concomitants of arousal and emotional states have utilized a variety of stimuli to evoke pertinent reactions. One type frequently used consists of visual stimuli in which nude or seminude human figures are depicted in still photographs or movies. Several investigations have found differences in physiological response patterns between this type of pictorial stimulus and other types of pictorial emotional stimuli (Koegler and Kline, 1965; Davis, 1967; Davis and Buckwald, 1957; Lazarus et al, 1963; Lifshitz, 1966). Differences in magnitude of physiological response to varied types of visual sexual stimuli have been found in studies of deviant sexual orientation (Solyom and Beck, 1967; McConaghy, 1967; Freund et al, 1958; Hess et al, 1965). Levitt and Hinesley (1967) studied the valences of erotic visual stimuli in normal subjects, but without regard to physiological variables. Except for studies by Loiselle and Mollenauer (1965), Koegler and Kline (1965), and McConaghy (1967), there has been little attention given to different types of pictorial sexual stimuli and physiological response in normal individuals, nor to the author's knowledge, have relationships been investigated between physiological responses and the different possible emotional connotations or meanings that sexual visual stimuli may have for normal subjects, other than roughly classifying the stimuli as male or female, or as nude or semi-nude.

On certain physiologic responses to intravenous injection of calcium salts into normal hyperparathyroid and hypoparathyroid persons.

THE exact functional activities of the parathyroid hormone have not as yet been clearly defined, and it is often difficult for the physician to discern the functional status of the parathyroid glands. Some observations to be reported here on the response of normal individuals and of patients with abnormal parathyroid function to intravenous administration of calcium salts appear to throw some light on parathyroid physiology.

Lymphocytic response of normal individuals to transient hyper- and hypoglycemia.

SummaryThe intravenous administration of 25 g of glucose in 50% solution was accompanied by a significant lymphocytopenia which reached its lowest level at 1/2 to 1 hour in 5 normal subjects and at 2 hours in the sixth. The intravenous administration of 0.075 unit of regular insulin per kilo of body weight evoked a significant absolute lymphocytosis which reached its peak at 45 to 60 minutes in 7 normal persons, and at 120 minutes in the eighth. The lymphocytopenia after glucose administration is inferred to be a result of adrenocortical stimulation caused by the change in the blood sugar level. The absolute lymphocytosis after insulin is similarly assumed to result from adrenocortical inhibition due to the moderate hypoglycemia. The discrepancy between our findings and those of others, who noted a decrease of lymphocytes following insulin, is explained by the small amounts of insulin used by us, thus avoiding shock and concomitant adrenocortical stimulation. This study suggests that the response of the a...